Bcl 2

Summary

Gene Symbol: Bcl 2
Description: BCL2, apoptosis regulator
Alias: Bcl-2, PPP1R50, apoptosis regulator Bcl-2, B-cell CLL/lymphoma 2, protein phosphatase 1, regulatory subunit 50
Species: human

Top Publications

  1. pmc Characterization of the signal that directs Bcl-x(L), but not Bcl-2, to the mitochondrial outer membrane
    Thomas Kaufmann
    Institute of Molecular Medicine and Cell Research, Albert Ludwigs University Freiburg, D 79106 Freiburg, Germany
    J Cell Biol 160:53-64. 2003
  2. ncbi Bcl-2 and Bcl-XL regulate proinflammatory caspase-1 activation by interaction with NALP1
    Jean Marie Bruey
    Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Cell 129:45-56. 2007
  3. pmc Antagonism of Beclin 1-dependent autophagy by BCL-2 at the endoplasmic reticulum requires NAF-1
    Natasha C Chang
    Department of Biochemistry and Goodman Cancer Center, McGill University, Montreal, Quebec, Canada
    EMBO J 29:606-18. 2010
  4. ncbi The Bcl2 family: regulators of the cellular life-or-death switch
    Suzanne Cory
    The Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Victoria 3050, Australia
    Nat Rev Cancer 2:647-56. 2002
  5. pmc The BH3 alpha-helical mimic BH3-M6 disrupts Bcl-X(L), Bcl-2, and MCL-1 protein-protein interactions with Bax, Bak, Bad, or Bim and induces apoptosis in a Bax- and Bim-dependent manner
    Aslamuzzaman Kazi
    Drug Discovery Department, Moffitt Cancer Center, University of South Florida, Tampa, Florida 33612, USA
    J Biol Chem 286:9382-92. 2011
  6. pmc Apoptosis protection by Mcl-1 and Bcl-2 modulation of inositol 1,4,5-trisphosphate receptor-dependent Ca2+ signaling
    Emily F Eckenrode
    Department of Physiology and Biophysics, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois 60064, USA
    J Biol Chem 285:13678-84. 2010
  7. ncbi Discovery of small-molecule inhibitors of Bcl-2 through structure-based computer screening
    I J Enyedy
    Structural Biology and Cancer Drug Discovery Program, Lombardi Cancer Center and Department of Oncology, Georgetown University Medical Center, 3970 Reservoir Road, Washington, DC 20007, USA
    J Med Chem 44:4313-24. 2001
  8. pmc The stress protein BAG3 stabilizes Mcl-1 protein and promotes survival of cancer cells and resistance to antagonist ABT-737
    Mariana Boiani
    Department of Biochemistry, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    J Biol Chem 288:6980-90. 2013
  9. ncbi Tumor necrosis factor alpha polymorphism associated with increased susceptibility to development of adult T-cell leukemia/lymphoma in human T-lymphotropic virus type 1 carriers
    K Tsukasaki
    Division of Hematology Oncology, Cedars Sinai Medical Center, University of California at Los Angeles School of Medicine, 90024, USA
    Cancer Res 61:3770-4. 2001
  10. pmc HIV-1 Tat protein promotes neuronal dysfunction through disruption of microRNAs
    J Robert Chang
    Department of Neurology, Molecular Studies of Neurodegenerative Diseases Laboratory, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA
    J Biol Chem 286:41125-34. 2011

Research Grants

  1. Douglas R Green; Fiscal Year: 2016
  2. Mechanisms of Hypothermic Protection from Ischemia/Reperfusion Cardiac Injury
    Kimm J Hamann; Fiscal Year: 2010
  3. Shai Shaham; Fiscal Year: 2016
  4. Modulation of Apoptosis by IRF-4 in EBV transformation
    Luwen Zhang; Fiscal Year: 2010
  5. Signaling Cell Death from the Endoplasmic Reticulum
    Scott A Oakes; Fiscal Year: 2013
  6. FDRC1 AND FOLLICULAR DENDRITIC CELL SIGNALING PATHWAYS
    Edward A Clark; Fiscal Year: 2013
  7. J Marie Hardwick; Fiscal Year: 2014
  8. Rona G Giffard; Fiscal Year: 2016
  9. Regulation of mitochondrial oxidative stress by Bcl-2 family proteins
    DANIEL LINSEMAN; Fiscal Year: 2011
  10. Mcl-1 as an essential regulator of cardiac mitochondrial function
    Asa B Gustafsson; Fiscal Year: 2013

Detail Information

Publications381 found, 100 shown here

  1. pmc Characterization of the signal that directs Bcl-x(L), but not Bcl-2, to the mitochondrial outer membrane
    Thomas Kaufmann
    Institute of Molecular Medicine and Cell Research, Albert Ludwigs University Freiburg, D 79106 Freiburg, Germany
    J Cell Biol 160:53-64. 2003
    ..These data define a new targeting sequence for the MOM and propose that Bcl-2 acts on several intracellular membranes whereas Bcl-x(L) specifically functions on the MOM...
  2. ncbi Bcl-2 and Bcl-XL regulate proinflammatory caspase-1 activation by interaction with NALP1
    Jean Marie Bruey
    Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Cell 129:45-56. 2007
    ..The findings reveal an interaction of host defense and apoptosis machinery...
  3. pmc Antagonism of Beclin 1-dependent autophagy by BCL-2 at the endoplasmic reticulum requires NAF-1
    Natasha C Chang
    Department of Biochemistry and Goodman Cancer Center, McGill University, Montreal, Quebec, Canada
    EMBO J 29:606-18. 2010
    ..NAF-1 is required in this pathway for BCL-2 at the ER to functionally antagonize Beclin 1-dependent autophagy. Thus, NAF-1 is a BCL-2-associated co-factor that targets BCL-2 for antagonism of the autophagy pathway at the ER...
  4. ncbi The Bcl2 family: regulators of the cellular life-or-death switch
    Suzanne Cory
    The Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Victoria 3050, Australia
    Nat Rev Cancer 2:647-56. 2002
    ..Apoptosis is often impaired in cancer and can limit conventional therapy. A better understanding of how the Bcl2 family controls caspase activation should result in new, more effective therapeutic approaches...
  5. pmc The BH3 alpha-helical mimic BH3-M6 disrupts Bcl-X(L), Bcl-2, and MCL-1 protein-protein interactions with Bax, Bak, Bad, or Bim and induces apoptosis in a Bax- and Bim-dependent manner
    Aslamuzzaman Kazi
    Drug Discovery Department, Moffitt Cancer Center, University of South Florida, Tampa, Florida 33612, USA
    J Biol Chem 286:9382-92. 2011
    ..Finally, BH3-M6 sensitizes cells to apoptosis induced by the proteasome inhibitor CEP-1612...
  6. pmc Apoptosis protection by Mcl-1 and Bcl-2 modulation of inositol 1,4,5-trisphosphate receptor-dependent Ca2+ signaling
    Emily F Eckenrode
    Department of Physiology and Biophysics, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois 60064, USA
    J Biol Chem 285:13678-84. 2010
    ..Our data suggest a molecular mechanism that is shared by several anti-apoptotic Bcl-2 proteins that provides apoptosis resistance by direct interactions at the ER with the InsP(3)R that impinges on cellular Ca(2+) homeostasis...
  7. ncbi Discovery of small-molecule inhibitors of Bcl-2 through structure-based computer screening
    I J Enyedy
    Structural Biology and Cancer Drug Discovery Program, Lombardi Cancer Center and Department of Oncology, Georgetown University Medical Center, 3970 Reservoir Road, Washington, DC 20007, USA
    J Med Chem 44:4313-24. 2001
    ..Our results suggest that the structure-based computer screening strategy employed in the study is effective for identifying novel, structurally diverse, nonpeptide small-molecule inhibitors that target the BH3 binding site of Bcl-2...
  8. pmc The stress protein BAG3 stabilizes Mcl-1 protein and promotes survival of cancer cells and resistance to antagonist ABT-737
    Mariana Boiani
    Department of Biochemistry, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    J Biol Chem 288:6980-90. 2013
    ..These studies identify BAG3-mediated Mcl-1 stabilization as a potential target for cancer drug discovery...
  9. ncbi Tumor necrosis factor alpha polymorphism associated with increased susceptibility to development of adult T-cell leukemia/lymphoma in human T-lymphotropic virus type 1 carriers
    K Tsukasaki
    Division of Hematology Oncology, Cedars Sinai Medical Center, University of California at Los Angeles School of Medicine, 90024, USA
    Cancer Res 61:3770-4. 2001
    ....
  10. pmc HIV-1 Tat protein promotes neuronal dysfunction through disruption of microRNAs
    J Robert Chang
    Department of Neurology, Molecular Studies of Neurodegenerative Diseases Laboratory, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA
    J Biol Chem 286:41125-34. 2011
    ..Therefore, we conclude that deregulation of neuronal functions by HIV-1 Tat protein is miRNA-dependent...
  11. pmc Distribution of Bim determines Mcl-1 dependence or codependence with Bcl-xL/Bcl-2 in Mcl-1-expressing myeloma cells
    Alejo A Morales
    Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA
    Blood 118:1329-39. 2011
    ..Overall, these results suggest that complex interactions, and not simply expression patterns of Bcl-2 proteins, need to be investigated to understand Bcl-2 dependence and how to better use agents, such as ABT-737...
  12. ncbi HIV-1-Tat protein activates phosphatidylinositol 3-kinase/ AKT-dependent survival pathways in Kaposi's sarcoma cells
    Maria Chiara Deregibus
    Cattedra di Nefrologia, Dipartimento di Medicina Interna Università di Torino, Centro Ricerca Medicina Sperimentale CeRMS, Italy
    J Biol Chem 277:25195-202. 2002
    ....
  13. pmc Mechanism of regulation of bcl-2 mRNA by nucleolin and A+U-rich element-binding factor 1 (AUF1)
    Daniella Ishimaru
    Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    J Biol Chem 285:27182-91. 2010
    ..Based on our findings, we propose a model that illustrates the opposing roles of nucleolin and AUF1 in regulating bcl-2 mRNA stability...
  14. pmc The intracellular distribution and pattern of expression of Mcl-1 overlap with, but are not identical to, those of Bcl-2
    T Yang
    Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755 3835
    J Cell Biol 128:1173-84. 1995
    ..A burst of expression of mcl-1, prominently associated with mitochondria, complements the continued expression of bcl-2 in ML-1 cells differentiating along the monocyte/macrophage pathway...
  15. pmc Bim upregulation by histone deacetylase inhibitors mediates interactions with the Bcl-2 antagonist ABT-737: evidence for distinct roles for Bcl-2, Bcl-xL, and Mcl-1
    Shuang Chen
    Department of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA
    Mol Cell Biol 29:6149-69. 2009
    ....
  16. ncbi Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death
    Z N Oltvai
    Howard Hughes Medical Institute Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110
    Cell 74:609-19. 1993
    ..Overexpressed Bax also counters the death repressor activity of Bcl-2. These data suggest a model in which the ratio of Bcl-2 to Bax determines survival or death following an apoptotic stimulus...
  17. ncbi Prognostic relevance of a novel semiquantitative classification of Bcl2 immunohistochemical expression in human infiltrating ductal carcinomas of the breast
    D Trere
    Department of Experimental Pathology, Unit of Clinical Pathology, University of Bologna, Italy
    Ann Oncol 18:1004-14. 2007
    ..In the present study, we evaluated the clinical relevance of a novel, semiquantitative classification of the Bcl2 immunostaining based on both the distribution and the intensity of the staining reaction...
  18. doi Prognostic significance of COX-2 expression and correlation with Bcl-2 and VEGF expression, microvessel density, and clinical variables in classical Hodgkin lymphoma
    Young Wha Koh
    Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
    Am J Surg Pathol 37:1242-51. 2013
    ..013). COX-2 and VEGF correlated with angiogenesis and tumor progression in cHL. The findings support targeting COX-2 as a potential new therapeutic approach in cHL. ..
  19. pmc Correlation between chemosensitivity to anticancer drugs and Bcl-2 expression in gastric cancer
    Ming Geng
    Department of Pathology, General Hospital of Jinan Military Command Jinan, China
    Int J Clin Exp Pathol 6:2554-9. 2013
    ..To investigate chemoresistance of human gastric cancer to chemotherapeutic drugs in vitro and explore the relationship with Bcl-2 protein expression...
  20. ncbi BCL-2, BAX and P53 expression profiles in endometrial carcinoma as studied by real-time PCR and immunohistochemistry
    Ourania Porichi
    Department of Virology, Papanikolaou Research Center of Oncology and Experimental Surgery, Aghios Savvas, Regional Anticancer Oncology Hospital of Athens, 171 Alexandras Ave, 115 22, Athens, Greece
    Anticancer Res 29:3977-82. 2009
    ..Apoptotic genes regulate apoptosis by the action of their pro- and antiapoptotic products. Among the most important proteins are p53 and Bcl-x family proteins...
  21. ncbi Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone promotes functional cooperation of Bcl2 and c-Myc through phosphorylation in regulating cell survival and proliferation
    Zhaohui Jin
    University of Florida Shands Cancer Center, Department of Medicine, University of Florida, Gainesville, Florida 32610 0232, USA
    J Biol Chem 279:40209-19. 2004
    ....
  22. doi Upregulation of Beclin-1 expression and phosphorylation of Bcl-2 and p53 are involved in the JNK-mediated autophagic cell death
    Kyung Jin Park
    Dept of Molecular Science and Technology, Ajou University, Yeongtong Gu, Suwon, Republic of Korea
    Biochem Biophys Res Commun 382:726-9. 2009
    ..Our results suggest that DR5-stimulated JNK activation and its consequent fluxes into the pro-autophagic signaling pathways contribute to the autophagic cell death in cancer cells...
  23. ncbi Phosphorylation of Beclin 1 by DAP-kinase promotes autophagy by weakening its interactions with Bcl-2 and Bcl-XL
    Einat Zalckvar
    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    Autophagy 5:720-2. 2009
    ..Our results reveal a new phosphorylation-based mechanism that reduces the interaction of Beclin 1 with its inhibitors to activate the autophagic machinery...
  24. pmc Hypoxic human cancer cells are sensitized to BH-3 mimetic–induced apoptosis via downregulation of the Bcl-2 protein Mcl-1
    Luke R E Harrison
    Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, United Kingdom
    J Clin Invest 121:1075-87. 2011
    ....
  25. doi miR-15a/16-1 influences BCL2 expression in keratocystic odontogenic tumors
    Marina Gonçalves Diniz
    Department of Oral Surgery and Pathology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
    Cell Oncol (Dordr) 35:285-91. 2012
    ..The purpose of this study was to investigate whether the transcription of miR-15a and miR-16-1 is altered in KCOTs and whether it is associated with BCL2 gene expression in such lesions...
  26. pmc Proapoptotic BAX and BAK regulate the type 1 inositol trisphosphate receptor and calcium leak from the endoplasmic reticulum
    Scott A Oakes
    Howard Hughes Medical Institute, Dana Farber Cancer Institute, Brigham and Women s Hospital, Departments of Pathology and Medicine, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:105-10. 2005
    ..These findings support a model in which BCL-2 family members regulate IP3R-1 phosphorylation to control the rate of ER Ca(2+) leak from intracellular stores...
  27. pmc The HIV-1 vpr protein acts as a negative regulator of apoptosis in a human lymphoblastoid T cell line: possible implications for the pathogenesis of AIDS
    L Conti
    Laboratory of Virology, Istituto Superiore di Sanita, Viale Regina Elena, 299 00161 Rome, Italy
    J Exp Med 187:403-13. 1998
    ..This might explain why apoptosis mostly occurs in bystander uninfected cells in AIDS patients...
  28. ncbi Polyclonal proliferation and apoptosis of CCR5+ T lymphocytes during primary human immunodeficiency virus type 1 infection: regulation by interleukin (IL)-2, IL-15, and Bcl-2
    John J Zaunders
    Centre for Immunology, St Vincent s Hospital, Darlinghurst, New South Wales, Australia
    J Infect Dis 187:1735-47. 2003
    ..Understanding cytokine effects on CCR5(+) T cells will be important in understanding chronic HIV-1 replication and pathogenesis...
  29. pmc Apoptotic regulation by MCL-1 through heterodimerization
    Qian Liu
    Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada
    J Biol Chem 285:19615-24. 2010
    ..We also present the solution structure of complex cMCL-1xhBID-BH3, which completes the family portrait of MCL-1 complexes and may facilitate drug discovery against human tumors...
  30. doi Bcl-2 suppresses Ca2+ release through inositol 1,4,5-trisphosphate receptors and inhibits Ca2+ uptake by mitochondria without affecting ER calcium store content
    C Jane Hanson
    Laboratory of Molecular Signalling, Babraham Institute, Babraham, Cambridge CB2 4AT, UK
    Cell Calcium 44:324-38. 2008
    ..Our data suggest that the presence of Bcl-2 in the proteome of cells has multiple effects on agonist-mediated Ca2+ signals, and can abrogate responses to submaximal levels of stimulation through direct control of InsP3Rs...
  31. ncbi BNIP3 heterodimerizes with Bcl-2/Bcl-X(L) and induces cell death independent of a Bcl-2 homology 3 (BH3) domain at both mitochondrial and nonmitochondrial sites
    R Ray
    Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Manitoba R3E 0V9, Canada
    J Biol Chem 275:1439-48. 2000
    ..We propose that BNIP3 represents a subfamily of Bcl-2-related proteins that functions without a typical BH3 domain to regulate apoptosis from both mitochondrial and nonmitochondrial sites by selective Bcl-2/Bcl-X(L) interactions...
  32. doi Coxiella burnetii modulates Beclin 1 and Bcl-2, preventing host cell apoptosis to generate a persistent bacterial infection
    C L Vazquez
    Laboratorio de Biología Celular y Molecular Instituto de Histología y Embriología IHEM, Facultad de Ciencias Medicas, Universidad Nacional de Cuyo CONICET, Mendoza, Argentina
    Cell Death Differ 17:421-38. 2010
    ..Overall, these findings indicate that C. burnetii infection modulates autophagy and apoptotic pathways through Beclin 1/Bcl-2 interplay to establish a successful infection in the host cell...
  33. pmc Apoptosis mediated by HIV protease is preceded by cleavage of Bcl-2
    P R Strack
    Molecular Biology Department, DuPont Merck Pharmaceutical Company, Wilmington, DE 19880 0336, USA
    Proc Natl Acad Sci U S A 93:9571-6. 1996
    ..Purified bcl-2 is cleaved by HIV protease between phenylalanine 112 and alanine 113. The results suggest a new option for HIV gene therapy; bcl-2 muteins that have noncleavable alterations surrounding the HIV protease cleavage site...
  34. ncbi A functional role for mitochondrial protein kinase Calpha in Bcl2 phosphorylation and suppression of apoptosis
    P P Ruvolo
    Sealy Center for Oncology and Hematology and the Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555, USA
    J Biol Chem 273:25436-42. 1998
    ..Collectively, these findings identify a functional role for PKCalpha in Bcl2 phosphorylation and in resistance to chemotherapy and suggest a novel target for antileukemic strategies...
  35. pmc Sepia ink oligopeptide induces apoptosis in prostate cancer cell lines via caspase-3 activation and elevation of Bax/Bcl-2 ratio
    Fangfang Huang
    School of Food science and Pharmacy, Zhejiang Provincial Key Engineering Technology Research Center of Marine Biomedical Products, Zhejiang Ocean University, Zhoushan 316000, China
    Mar Drugs 10:2153-65. 2012
    ..Moreover, the Bax/Bcl-2expression ratio was increased. Concurrently, the expression of caspase-3 was upregulated. These data support our hypothesis that SIO has anticarcinogenic properties...
  36. doi A BACH2-BCL2L1 fusion gene resulting from a t(6;20)(q15;q11.2) chromosomal translocation in the lymphoma cell line BLUE-1
    Seval Turkmen
    Institut fur Medizinische Genetik, Charité CVK, Berlin, Germany
    Genes Chromosomes Cancer 50:389-96. 2011
    ..Moreover, it suggests that members of the BCL2 anti-apoptosis gene family other than BCL2 itself might also be involved in lymphoma...
  37. pmc Blood myeloid dendritic cells from HIV-1-infected individuals display a proapoptotic profile characterized by decreased Bcl-2 levels and by caspase-3+ frequencies that are associated with levels of plasma viremia and T cell activation in an exploratory st
    Stephanie M Dillon
    Department of Medicine, University of Colorado Denver, Aurora, Colorado 80045, USA
    J Virol 85:397-409. 2011
    ....
  38. doi Bcl-2 SNP rs956572 associates with disrupted intracellular calcium homeostasis in bipolar I disorder
    Takuji Uemura
    Laboratory of Cellular and Molecular Pathophysiology, Centre for Addiction and Mental Health Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
    Bipolar Disord 13:41-51. 2011
    ..We sought to evaluate the impact of this variant on ICH in BD...
  39. pmc A growth factor attenuates HIV-1 Tat and morphine induced damage to human neurons: implication in HIV/AIDS-drug abuse cases
    Shaily Malik
    Cellular and Molecular Neuroscience, National Brain Research Center, Manesar, Gurgaon, Haryana, India
    PLoS ONE 6:e18116. 2011
    ..We have also showed for the first time that PDGF-BB can protect against simultaneous exposure of Tat and morphine, strengthening its role as a neuroprotective agent that could be considered for therapeutic intervention...
  40. ncbi Human immunodeficiency virus type 1 Tat protein modulates cell cycle and apoptosis in Epstein-Barr virus-immortalized B cells
    Eva Colombrino
    Department of Oncology and Surgical Sciences, Section of Oncology, University of Padova, Padua, Italy
    Exp Cell Res 295:539-48. 2004
    ....
  41. ncbi Id-1 regulates Bcl-2 and Bax expression through p53 and NF-kappaB in MCF-7 breast cancer cells
    Hwan Kim
    Department of Pathology, College of Medicine, Hanyang University, Seongdong Gu, Seoul, Republic of Korea
    Breast Cancer Res Treat 112:287-96. 2008
    ..In this regard, inactivation of Id-1 may provide a potential therapeutic strategy leading to inhibition of breast cancer progression and anti-cancer drug resistance...
  42. pmc Involvement of BH4 domain of bcl-2 in the regulation of HIF-1-mediated VEGF expression in hypoxic tumor cells
    D Trisciuoglio
    Experimental Chemotherapy Laboratory, Experimental Oncology Department, Regina Elena Cancer Institute, Rome, Italy
    Cell Death Differ 18:1024-35. 2011
    ..Finally, we found that the mechanism by which bcl-2 regulates HIF-1-mediated VEGF expression does not require BH1 and BH2 domains, and it is independent of antiapoptotic and prosurvival function of bcl-2...
  43. ncbi Bcl-2 targets protein phosphatase 1 alpha to Bad
    V Ayllon
    Department of Immunology and Oncology, Centro Nacional de Biotecnologia, Campus de Cantoblanco, Madrid, Spain
    J Immunol 166:7345-52. 2001
    ..Disruption of Bcl-2/PP1alpha association strongly decreased Bcl-2 and Bad-associated phosphatase activity and formation of the trimolecular complex. These results suggest that Bcl-2 targets PP1alpha to Bad...
  44. ncbi Comparison of benign keratoses using p53, bcl-1, and bcl-2
    Christine J Ko
    Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA
    J Cutan Pathol 32:356-9. 2005
    ..Keratinocyte bcl-2 staining was significantly higher in SKs compared with the other two keratoses. Bcl-2 may be increased in SKs as an anti-apoptotic mechanism...
  45. ncbi [Effect of combined therapy with Chinese drug and narrow broad ultraviolet B on Bcl-2, caspase-3 and survivin in skin lesion with psoriasis vulgaris]
    Lan Ying Qin
    Department of Dermatology, Cangzhou People s Hospital, Hebei
    Zhongguo Zhong Xi Yi Jie He Za Zhi 30:706-9. 2010
    ..To reveal the possible role of combined therapy with Chinese drug and narrow broad ultraviolet B (NB-UVB) on keratinocytes apoptosis in skin lesion of psoriasis vulgaris (PV)...
  46. ncbi Interleukin-3 and bryostatin-1 mediate hyperphosphorylation of BCL2 alpha in association with suppression of apoptosis
    W S May
    Johns Hopkins Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231
    J Biol Chem 269:26865-70. 1994
    ..These findings strongly support a role for activated PKC in growth factor-induced Bc12 alpha phosphorylation as well as suppression of apoptosis...
  47. ncbi Regression of lymphoproliferative disorder after treatment for hepatitis C virus infection in a patient with partial trisomy 3, Bcl-2 overexpression, and type II cryoglobulinemia
    Milvia Casato
    Department of Clinical Medicine, University of Rome La Sapienza, Rome, Italy
    Blood 99:2259-61. 2002
    ..Further studies of HCV-infected patients with and without type II cryoglobulinemia are required to determine the prevalence and possible physiologic and/or pathophysiologic significance of these findings...
  48. ncbi Signal transduction from N-cadherin increases Bcl-2. Regulation of the phosphatidylinositol 3-kinase/Akt pathway by homophilic adhesion and actin cytoskeletal organization
    Nhan L Tran
    Cancer Biology Graduate Program, University of Arizona Health Sciences Center, Tucson, Arizona 85724, USA
    J Biol Chem 277:32905-14. 2002
    ..We propose that N-cadherin homophilic adhesion can initiate anti-apoptotic signaling, which enhances the Akt cell survival pathway in metastatic cancer...
  49. ncbi Progesterone receptor modulator CDB-2914 down-regulates proliferative cell nuclear antigen and Bcl-2 protein expression and up-regulates caspase-3 and poly(adenosine 5'-diphosphate-ribose) polymerase expression in cultured human uterine leiomyoma cells
    Qin Xu
    Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Chuo Ku, Kobe 650 0017, Japan
    J Clin Endocrinol Metab 90:953-61. 2005
    ....
  50. ncbi Bcl-2 overexpression in thyroid carcinoma cells increases sensitivity to Bcl-2 homology 3 domain inhibition
    Constantine S Mitsiades
    Department of Medical Oncology, Dana Farber Cancer Institute, Mayer Building, Room M555, 44 Binney Street, Boston, Massachusetts 02115, USA
    J Clin Endocrinol Metab 92:4845-52. 2007
    ..The Bcl-2 family of proteins regulates apoptosis in various models and may represent a promising therapeutic target in human malignancies...
  51. doi Developmental patterns of caspase-3, bax and bcl-2 proteins expression in the human spinal ganglia
    Katarina Vukojevic
    Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, 21000 Split, Croatia
    J Mol Histol 39:339-49. 2008
    ..While apoptosis might control cell number, bcl-2 could act in suppression of apoptosis and enhancement of cell differentiation...
  52. pmc Bcl-2 and Bax interact via the BH1-3 groove-BH3 motif interface and a novel interface involving the BH4 motif
    Jingzhen Ding
    Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73126, USA
    J Biol Chem 285:28749-63. 2010
    ..As expected, both kinds of mutation abolished Bcl-2-mediated inhibition of Bax oligomerization in detergent micelles. Therefore, Bcl-2 binds Bax through two interdependent interfaces to inhibit the pro-apoptotic oligomerization of Bax...
  53. ncbi Human immunodeficiency virus type 1 Tat protein protects lymphoid, epithelial, and neuronal cell lines from death by apoptosis
    G Zauli
    Institute of Human Anatomy, University of Ferrara, Italy
    Cancer Res 53:4481-5. 1993
    ....
  54. ncbi BCL-2 and BCL-XL restrict lineage choice during hematopoietic differentiation
    Loralee Haughn
    Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    J Biol Chem 278:25158-65. 2003
    ..These effects are associated with differential regulation of Raf-1 expression, perhaps involving the previously identified interaction between BCL-2-BH4 and the catalytic domain of Raf-1...
  55. ncbi Identification of nucleolin as an AU-rich element binding protein involved in bcl-2 mRNA stabilization
    Tapas K Sengupta
    Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    J Biol Chem 279:10855-63. 2004
    ....
  56. pmc Parkin mono-ubiquitinates Bcl-2 and regulates autophagy
    Dong Chen
    Laboratory of Molecular Neuropathology, School of Life Sciences, University of Science and Technology of China, Chinese Academy of Sciences, Hefei, Anhui 230027, China
    J Biol Chem 285:38214-23. 2010
    ..Moreover, overexpression of parkin enhances the interactions between Bcl-2 and Beclin 1. Our results provide evidence that parkin mono-ubiquitinates Bcl-2 and regulates autophagy via Bcl-2...
  57. ncbi Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members
    Michael Certo
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Cancer Cell 9:351-65. 2006
    ..Our data allow us to distinguish a cellular state we call "primed for death," which can be determined by BH3 profiling and which correlates with dependence on antiapoptotic family members for survival...
  58. pmc Expression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancer
    Yasmine Nadler
    Department of Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
    Breast Cancer Res 10:R35. 2008
    ....
  59. pmc Bax activation by the BH3-only protein Puma promotes cell dependence on antiapoptotic Bcl-2 family members
    Tristan Gallenne
    Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 892, Département de Recherche en Cancérologie, F 44035 Nantes, Cedex 01, France
    J Cell Biol 185:279-90. 2009
    ..Thus, Puma is competent to trigger Bax activity by itself, thereby promoting cellular dependence on prosurvival Bcl-2 family members...
  60. doi Bcl-2 overexpression attenuates SP600125-induced apoptosis in human leukemia U937 cells
    Dong Oh Moon
    Faculty of Applied Marine Science, Cheju National University, Jeju Special Self Governing Province 690 756, South Korea
    Cancer Lett 264:316-25. 2008
    ..These data provide important mechanistic insights related to Bcl-2-mediated resistance to SP600125-induced apoptosis, and induction of G2/M phase arrest and endoreduplication...
  61. ncbi The flexible loop of Bcl-2 is required for molecular interaction with immunosuppressant FK-506 binding protein 38 (FKBP38)
    Cong Bao Kang
    Division of Structural and Computational Biology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637511, Singapore
    FEBS Lett 579:1469-76. 2005
    ..Here, we investigated the molecular interaction between FKBP38 and Bcl-2, and demonstrated that Bcl-2 interacts with FKBP38 through the unstructured loop, and the interaction appears to regulate phosphorylation in the loop of Bcl-2...
  62. pmc Bcl-2 retards cell cycle entry through p27(Kip1), pRB relative p130, and altered E2F regulation
    G Vairo
    The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia
    Mol Cell Biol 20:4745-53. 2000
    ..Hence, Bcl-2 appears to retard cell cycle entry by increasing p27 and p130 levels and maintaining repressive complexes of p130 with E2F4, perhaps to delay E2F1 expression...
  63. ncbi BCL-x(L) and BCL2 delay Myc-induced cell cycle entry through elevation of p27 and inhibition of G1 cyclin-dependent kinases
    Courtney Greider
    Department of Cancer Biology, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, TN 37232, USA
    Oncogene 21:7765-75. 2002
    ..Our results suggest that one possible mechanism by which BCL-x(L) and BCL2 delay cell cycle entry may be the inhibition of Myc activity through the elevation of p27...
  64. ncbi Breast cancer cells can evade apoptosis-mediated selective killing by a novel small molecule inhibitor of Bcl-2
    Pedro Jose Real
    Unidad de Genetica Molecular and Servicio de Oncologia Medica, Hospital Universitario Marques de Valdecilla, Servicio Cantabro de Salud, Santander, Spain
    Cancer Res 64:7947-53. 2004
    ..Consistently, HER2 blockade led to YC137 resistance. These data provide evidence for the selective killing of tumor cells by YC137 and represent the first example of in vitro selection of cancer cells refractory to a Bcl-2 inhibitor...
  65. pmc Functional and physical interaction between Bcl-X(L) and a BH3-like domain in Beclin-1
    M Chiara Maiuri
    INSERM U848, Villejuif, France
    EMBO J 26:2527-39. 2007
    ..BH3-only proteins and pharmacological BH3 mimetics induce autophagy by competitively disrupting the interaction between Beclin-1 and Bcl-2 or Bcl-X(L)...
  66. pmc The BH4 domain of Bcl-2 inhibits ER calcium release and apoptosis by binding the regulatory and coupling domain of the IP3 receptor
    Yi Ping Rong
    Departments of Medicine and Pharmacology, Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA
    Proc Natl Acad Sci U S A 106:14397-402. 2009
    ..By inhibiting proapoptotic Ca(2+) signals at their point of origin, the Bcl-2 BH4 domain has the facility to block diverse pathways through which Ca(2+) induces apoptosis...
  67. ncbi Expression of human immunodeficiency virus type I tat results in down-regulation of bcl-2 and induction of apoptosis in hematopoietic cells
    K J Sastry
    Department of Veterinary Sciences, University of Texas MD Anderson Cancer Center, Bastrop 78602, USA
    Oncogene 13:487-93. 1996
    ..While these results support reports in the literature of an active role for tat in inducing cell death in HIV-infected individuals, they point to a new mechanism involving Tat-mediated modulation of bcl-2 and bax...
  68. doi Bcl-2 complexed with Beclin-1 maintains full anti-apoptotic function
    I A Ciechomska
    Department of Biochemistry, University of Cambridge, Cambridge, UK
    Oncogene 28:2128-41. 2009
    ..Hence, although Beclin-1 contains a BH3-only motif typical of pro-apoptotic proteins, it is a negligible modulator of Bcl-2's anti-apoptotic function...
  69. doi The bcl2 -938CC genotype has poor prognosis and lower survival in renal cancer
    Hiroshi Hirata
    Department of Urology, San Francisco Veterans Affairs Medical Center and University of California San Francisco, San Francisco, California 94121, USA
    J Urol 182:721-7. 2009
    ..Therefore, we investigated the polymorphism at the bcl2 -938C/A site and its effects on clinical characteristics in patients with renal cell carcinoma...
  70. pmc Perturbation of the Bcl-2 network and an induced Noxa/Bcl-xL interaction trigger mitochondrial dysfunction after DNA damage
    Hernando Lopez
    Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198 7696, USA
    J Biol Chem 285:15016-26. 2010
    ..These results suggest that the loss/inactivation of Mcl-1 in conjunction with an induced Noxa/Bcl-xL interaction may serve as a trigger for mitochondrial dysfunction during DNA damage-induced apoptosis...
  71. pmc IRGM is a common target of RNA viruses that subvert the autophagy network
    Isabel Pombo Gregoire
    Universite de Lyon, Lyon, France
    PLoS Pathog 7:e1002422. 2011
    ..Our work reveals an unexpected role of IRGM in virus-induced autophagy and suggests that several different families of RNA viruses may use common strategies to manipulate autophagy to improve viral infectivity...
  72. ncbi Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability
    Gael G McGill
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Cell 109:707-18. 2002
    ..This linkage helps explain the vital roles of both Mitf and Bcl2 in the melanocyte lineage and the well-known treatment resistance of melanoma...
  73. ncbi The C-terminal moiety of HIV-1 Vpr induces cell death via a caspase-independent mitochondrial pathway
    T Roumier
    Centre National de la Recherche Scientifique, UMR1599, Institut Gustave Roussy, 39 rue Camille Desmoulins, F 94805 Villejuif, France
    Cell Death Differ 9:1212-9. 2002
    ..In conclusion, it appears that Vpr induces apoptosis through a caspase-independent mitochondrial pathway...
  74. doi Bcl2 -938C/A polymorphism carries increased risk of biochemical recurrence after radical prostatectomy
    Hiroshi Hirata
    Department of Urology, San Francisco Veterans Affairs Medical Center and University of California San Francisco, San Francisco, California, USA
    J Urol 181:1907-12. 2009
    ..We investigated several polymorphisms related to the cell cycle and apoptosis, and their role in biochemical failure after radical prostatectomy...
  75. doi Gambogic acid reduced bcl-2 expression via p53 in human breast MCF-7 cancer cells
    Hongyan Gu
    Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, P O Box 209, 24 Tongjia Xiang, 210009 Nanjing, Jiangsu, China
    J Cancer Res Clin Oncol 135:1777-82. 2009
    ..In this study, we investigated the correlation between p53 and bcl-2 in gambogic acid (GA)-induced apoptosis...
  76. ncbi Role of caspase 3-dependent Bcl-2 cleavage in potentiation of apoptosis by Bcl-2
    Ye Liang
    The Pediatric Center for Neuroscience, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Mol Pharmacol 61:142-9. 2002
    ..Caspase 3-mediated Bcl-2 cleavage therefore plays an important role in the potentiation by Bcl-2 of NCS-induced apoptosis...
  77. ncbi Resistance to chemotherapy-induced apoptosis via decreased caspase-3 activity and overexpression of antiapoptotic proteins in ovarian cancer
    Xiaokui Yang
    Division of Gynecological Oncology, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, Hubei, PR China
    J Cancer Res Clin Oncol 130:423-8. 2004
    ....
  78. ncbi Involvement of G proteins of the Rho family in the regulation of Bcl-2-like protein expression and caspase 3 activation by Gastrins
    Hong He
    Department of Surgery, University of Melbourne, Austin Health, Melbourne, Victoria 3084, Australia
    Cell Signal 20:83-93. 2008
    ..The findings offer potential targets for blocking the growth-stimulating effects of these gastrins...
  79. pmc Functional long-range interactions of the IgH 3' enhancers with the bcl-2 promoter region in t(14;18) lymphoma cells
    H Duan
    Center for Molecular Biology in Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA
    Oncogene 27:6720-8. 2008
    ..This study reveals a new aspect of the regulatory role of the IgH 3' enhancers on bcl-2 transcription in t(14;18) lymphomas...
  80. ncbi Nuclear partners of Bcl-2: Bax and PML
    R W M Hoetelmans
    Department of Surgery, Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands
    DNA Cell Biol 23:351-4. 2004
    ..These data show that binding of Bcl-2 with structurally and functionally related proteins extends to the nucleus, emphasizing its pivotal role in Bcl-2-mediated actions...
  81. ncbi Cell-cycle-associated markers and clinical outcome in human epithelial cancers: a tissue microarray study
    I Abdulkader
    Department of Pathology, School of Medicine, Clinical University Hospital, 15706 Santiago de Compostela, Spain
    Oncol Rep 14:1527-31. 2005
    ..We found that in most common epithelial cancers, regardless of origin, Bcl-2 appears to be the key biological factor influencing clinical behaviour...
  82. ncbi Bcl-2 is a prognostic marker in breast cancer independently of the Nottingham Prognostic Index
    Grace M Callagy
    Cancer Genomics Program, Department of Oncology, Hutchison Medical Research Council Research Centre, University of Cambridge, United Kingdom
    Clin Cancer Res 12:2468-75. 2006
    ..We validated the results in an independent series...
  83. ncbi Intronic single-nucleotide polymorphisms in Bcl-2 are associated with chronic obstructive pulmonary disease severity
    Makoto Sata
    Department of Cardiology, Pulmonology and Nephrology, Course of Internal Medicine and Therapeutics, Yamagata University School of Medicine, Yamagata, Japan
    Respirology 12:34-41. 2007
    ..The aim of this study was to investigate the genetic association of Bcl-2 gene with the level of lung function, that is, the severity, of COPD...
  84. doi BCL-2 expression is prognostic for improved survival in non-small cell lung cancer
    Daniel J Renouf
    Division of Medical Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada
    J Thorac Oncol 4:486-91. 2009
    ..We used a large patient population to identify immunohistochemical biomarkers to enable improved prognostication in patients with non-small cell lung carcinoma (NSCLC)...
  85. ncbi Ultrastructural localization of bcl-2 protein
    P Monaghan
    Department of Cell Biology and Experimental Pathology, Institute of Cancer Research, Sutton, Surrey, UK
    J Histochem Cytochem 40:1819-25. 1992
    ....
  86. pmc Alternative promoters and exons, somatic mutation and deregulation of the Bcl-2-Ig fusion gene in lymphoma
    M Seto
    Department of Medicine, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, MO 63110
    EMBO J 7:123-31. 1988
    ..5 h half-life, the Bcl-2--Ig gene revealed an inappropriately high rate of transcription for a mature B-cell. This indicates the translocated Bcl-2 allele has escaped normal control mechanisms...
  87. ncbi Bcl-2 targets the protein kinase Raf-1 to mitochondria
    H G Wang
    The Burnham Institute, Program on Apoptosis and Cell Death Research, La Jolla, California 92037, USA
    Cell 87:629-38. 1996
    ..Bcl-2 can therefore target Raf-1 to mitochondrial membranes, allowing this kinase to phosphorylate BAD or possibly other protein substrates involved in apoptosis regulation...
  88. ncbi Suppression of signalling through transcription factor NF-AT by interactions between calcineurin and Bcl-2
    F Shibasaki
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 386:728-31. 1997
    ..We propose that the ability of Bcl-2 to block NF-AT signalling is due to the sequestering of active calcineurin to the same domain of Bcl-2 which associates with Rad-1 (ref. 5), and that calcineurin may act in Bcl-2-regulated functions...
  89. ncbi BH3 domain of BAD is required for heterodimerization with BCL-XL and pro-apoptotic activity
    J Zha
    Howard Hughes Medical Institute, Department of Medicine and Pathology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 272:24101-4. 1997
    ..These results establish a critical role for a BH3 domain within BAD and provide evidence that BAD may function as a death ligand whose pro-apoptotic activity requires heterodimerization with BCL-XL...
  90. pmc The HIV-1 viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore
    E Jacotot
    Centre National de la Recherche Scientifique, F 94801 Villejuif, France
    J Exp Med 191:33-46. 2000
    ..Hence, Vpr induces apoptosis via a direct effect on the mitochondrial PTPC...
  91. pmc Survival function of ERK1/2 as IL-3-activated, staurosporine-resistant Bcl2 kinases
    X Deng
    University of Florida Shands Cancer Center, Gainesville, FL 32610 0232, USA
    Proc Natl Acad Sci U S A 97:1578-83. 2000
    ..In addition, although the mechanism of regulation of Bcl2 by phosphorylation is not yet clear, our results indicate that phosphorylation may functionally stabilize the Bcl2-Bax heterodimerization...
  92. ncbi A novel protein, RTN-XS, interacts with both Bcl-XL and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity
    S Tagami
    Department of Medical Genetics, Biomedical Research Center, Osaka University Graduate School of Medicine, Suita, Japan
    Oncogene 19:5736-46. 2000
    ..These results suggest that RTN family proteins can modulate the anti-apoptotic activity of Bcl-XL and Bcl-2 by binding with them and can change their localization to the ER...
  93. ncbi Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis
    H Puthalakath
    The Walter and Eliza Hall Institute of Medical Research, Melbourne, P O Royal Melbourne Hospital, 3050 Vic, Australia
    Science 293:1829-32. 2001
    ..Thus, at least two mammalian BH3-only proteins, Bmf and Bim, function to sense intracellular damage by their localization to distinct cytoskeletal structures...
  94. pmc Bcl-2 functionally interacts with inositol 1,4,5-trisphosphate receptors to regulate calcium release from the ER in response to inositol 1,4,5-trisphosphate
    Rui Chen
    Department of Medicine, Comprehensive Cancer Center, Case Western Reserve University and University Hospitals of Cleveland, OH 44106, USA
    J Cell Biol 166:193-203. 2004
    ..We suggest that this functional interaction of Bcl-2 with InsP3Rs inhibits InsP3R activation and thereby regulates InsP3-induced calcium release from the ER...
  95. ncbi JNK is associated with Bcl-2 and PP1 in mitochondria: paclitaxel induces its activation and its association with the phosphorylated form of Bcl-2
    Laetitia Brichese
    Universite Paul Sabatier, Toulouse, France
    Cell Cycle 3:1312-9. 2004
    ....
  96. ncbi The first alpha helix of Bax plays a necessary role in its ligand-induced activation by the BH3-only proteins Bid and PUMA
    Pierre Francois Cartron
    INSERM U601, 9 quai Moncousu, 44035 Nantes Cedex 035, France
    Mol Cell 16:807-18. 2004
    ..Thus, a specific interaction between Bax Halpha1 and their BH3 domains allows Bid and PUMA to function as "death agonists" of Bax, whereas Bad recruits Bax activity through a distinct pathway...
  97. pmc Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins
    Simon N Willis
    The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
    Genes Dev 19:1294-305. 2005
    ..The finding that different prosurvival proteins have selective roles has notable implications for the design of anti-cancer drugs that target the Bcl-2 family...
  98. pmc miR-15 and miR-16 induce apoptosis by targeting BCL2
    Amelia Cimmino
    Department of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus OH 43210, USA
    Proc Natl Acad Sci U S A 102:13944-9. 2005
    ..BCL2 repression by these microRNAs induces apoptopsis in a leukemic cell line model. Therefore, miR-15 and miR-16 are natural antisense Bcl2 interactors that could be used for therapy of Bcl2-overexpressing tumors...
  99. ncbi WT p53, but not tumor-derived mutants, bind to Bcl2 via the DNA binding domain and induce mitochondrial permeabilization
    York Tomita
    Department of Pathology, Stony Brook University, Stony Brook, New York 11794 8691, USA
    J Biol Chem 281:8600-6. 2006
    ....
  100. ncbi Association of a novel regulatory polymorphism (-938C>A) in the BCL2 gene promoter with disease progression and survival in chronic lymphocytic leukemia
    Holger Nuckel
    Department of Hematology, Medical Faculty, University of Duisburg Essen, Germany
    Blood 109:290-7. 2007
    ..034) together with disease stage at diagnosis (HR 2.5; P = .004) and ZAP-70 status (HR 3.0; P = .001). The BCL2-938AA genotype is associated with increased Bcl-2 expression and a novel unfavorable genetic marker in patients with B-CLL...
  101. ncbi S-nitrosylation of Bcl-2 inhibits its ubiquitin-proteasomal degradation. A novel antiapoptotic mechanism that suppresses apoptosis
    Neelam Azad
    Department of Pharmaceutical Sciences, West Virginia University, Morgantown, West Virginia 26506, USA
    J Biol Chem 281:34124-34. 2006
    ..These findings indicate a novel function of NO and its regulation of Bcl-2, which provides a key mechanism for the control of apoptotic cell death and cancer development...

Research Grants98

  1. Douglas R Green; Fiscal Year: 2016
    ..Successful completion of the proposed work will reveal fundamental new processes in the control of cell life and death. ..
  2. Mechanisms of Hypothermic Protection from Ischemia/Reperfusion Cardiac Injury
    Kimm J Hamann; Fiscal Year: 2010
    ....
  3. Shai Shaham; Fiscal Year: 2016
    ..Together, these studies should not only inform us about the process of LC death, but may yield important clues and reagents as to the etiology of polyQ-dependent neurodegenerative disease. ..
  4. Modulation of Apoptosis by IRF-4 in EBV transformation
    Luwen Zhang; Fiscal Year: 2010
    ..These experiments may identify the apoptosis. These experiments may identify critical mechanisms that IRF-4 uses to prevent apoptosis in EBV-transformed cells. ..
  5. Signaling Cell Death from the Endoplasmic Reticulum
    Scott A Oakes; Fiscal Year: 2013
    ..This projects sets out to define how cellular stress normally leads to apoptosis and what goes wrong with this process in cancer-in the hopes of finding new therapeutic targets through which to kill tumor cells. ..
  6. FDRC1 AND FOLLICULAR DENDRITIC CELL SIGNALING PATHWAYS
    Edward A Clark; Fiscal Year: 2013
    ..The proposed studies may also contribute to understanding of how E2 and OPG contribute to the development of inflammatory immune responses. ..
  7. J Marie Hardwick; Fiscal Year: 2014
    ..Therefore, we will delineate the mechanisms that explain how Bcl-xL regulates mitochondrial dynamics and enhances neuronal activity in healthy neurons. ..
  8. Rona G Giffard; Fiscal Year: 2016
    ..Overall this proposal exams a novel hypothesis: that miRNAs act as master regulators of chaperones and BCL2 family members influencing Ca2+ homeostasis, mitochondria-ER crosstalk, and outcome after cerebral ischemia. ..
  9. Regulation of mitochondrial oxidative stress by Bcl-2 family proteins
    DANIEL LINSEMAN; Fiscal Year: 2011
    ..PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page Continuation Format Page ..
  10. Mcl-1 as an essential regulator of cardiac mitochondrial function
    Asa B Gustafsson; Fiscal Year: 2013
    ..This project will provide important new insights into mitochondrial function in cardiac myocytes and how mitochondrial dysfunction contributes to development of cardiovascular disease. (End of Abstract) ..
  11. Nika N Danial; Fiscal Year: 2016
    ..The studies described in this proposal may lead to identification of a new therapeutic target in diabetes. ..
  12. The Cyto-Protective Role of Hexokinase II During Metabolic Stress
    JONATHAN MICHAEL GALL; Fiscal Year: 2012
    ..The proposed studies will provide molecular insights into the mechanism of renal cell death and may promote the development of therapeutic interventions for treating acute, ischemic renal failure. ..
  13. Bid regulation of cutaneous photodamage responses
    Laura Timares; Fiscal Year: 2010
    ..The results from these studies may uncover a new mechanism for controlling cancer and a possible new target for diagnostic or therapeutic applications. ..
  14. Reactivating Apoptosis in Refractory Cancer by Selective Targeting of MCL-1
    Michelle Stewart; Fiscal Year: 2010
    ....
  15. Mechanisms of Stress Induced Apoptosis in T-Cells
    Douglas R Green; Fiscal Year: 2011
    ..In this integrated approach to the problem of p53 function in apoptosis, we will elucidate the roles of p53 in the context of stress-induced apoptosis in mature and developing T cells. ..
  16. Xiao Kun Zhang; Fiscal Year: 2014
    ..Our proposed studies are anticipated to identify an important new survival signaling pathway in cancer cells, which may serve as a new drug target. ..
  17. IL3 GROWTH FACTOR SIGNALING
    William Stratford May; Fiscal Year: 2010
    ....
  18. Steven C Borkan; Fiscal Year: 2016
    ....
  19. Junxuan Lu; Fiscal Year: 2014
    ..These multiple targeting activities plus published work supporting anti- angiogenesis activity provide strong rationale for testing the efficacy of PGG for prostate cancer chemoprevention. ..
  20. ERBB4 in the Normal and Neoplastic Breast
    Frank E Jones; Fiscal Year: 2013
    ....
  21. Il-7 receptor signaling in lymphopoiesis
    Motonari Kondo; Fiscal Year: 2010
    ..The goal of this project is to elucidate the signaling pathways downstream of IL-7 receptor, which drive specific steps in lymphocyte development, and to determine the genes involved in this process. ..
  22. Apoptosis Control by Bcl-2 Family Members
    Craig B Thompson; Fiscal Year: 2012
    ....
  23. NIH Director's Pioneer Award
    Junying Yuan; Fiscal Year: 2009
    ..No Abstract provided ..
  24. Shu Ichi Matsuzawa; Fiscal Year: 2015
    ....
  25. Karen M Vasquez; Fiscal Year: 2016
    ....
  26. Maurizio Pellecchia; Fiscal Year: 2014
    ..The development of small molecule Mcl-1 inhibitors represent a promising route for the development of more effective combination therapies for the treatment of NSCLC. ..
  27. Comparative Mechanisms of Genomic Instability
    Karen M Vasquez; Fiscal Year: 2010
    ..These discoveries should begin to unravel the pathogenesis of diseases that are caused by genomic instability, and ultimately to the development of new approaches for treatment and prevention. ..
  28. Apoptosis and Trophoblast Fusion
    NEAL STEWART ROTE; Fiscal Year: 2010
    ..We will investigate those correlations by specifically inhibiting these proteins using peptide inhibitors and gene silencing. Additional studies will evaluate the role of signal transduction through NFB. ..
  29. Heat Shock-Induced Apoptosis
    Shawn B Bratton; Fiscal Year: 2012
    ..Thus, it is anticipated that the work proposed herein will significantly improve our understanding of how heat shock works in the clinic and may shed light on new pathways that can be exploited therapeutically in the future. ..
  30. NLR Family Proteins: Mechanisms and Regulation
    John C Reed; Fiscal Year: 2012
    ..The proposed project is relevant to several diseases with unmet medical needs, including autoimmunty, chronic inflammation, allergy, infection, and vaccines. ..
  31. TARGETS OF AMINO ACID RESTRICTION IN PROSTATE CANCER
    Gary G Meadows; Fiscal Year: 2009
    ..This research could serve as the basis for future development of more specific antimetastatic, anti-invasive, apoptosis-based therapies for human prostate cancer. ..
  32. Molecular Characterization of Neural Stem Cell Apoptosis
    KEVIN AARON ROTH; Fiscal Year: 2012
    ....
  33. FUNCTION OF THE BCL-2 PROTEIN
    DONALD EWERT; Fiscal Year: 1993
    ..These studies can help to define the molecular basis of B cell malignancy...
  34. PP2A B-beta a novel apoptosis regulator
    José Carlos Crispín; Fiscal Year: 2013
    ..Moreover, it represents a conceptual breakthrough in our understanding of the regulation of PP2A in a discrete function. ..
  35. P53 TRAFFICKING DURING CELL CYCLE
    Michael Clarke; Fiscal Year: 2000
    ..These studies will give insight into the molecular mechanism by Bcl-2 and Myc modulate p53 functions. ..
  36. Peixin Yang; Fiscal Year: 2016
    ....
  37. Anand K Iyer; Fiscal Year: 2016
    ....
  38. Robert M Friedlander; Fiscal Year: 2014
    ..Finally, we will determine if posttranslational modification of Rip2 is required for epigenetic gene regulation and subsequent neuronal death in HD using HD mice lacking expression of Rip2. ..
  39. Protein Nitration in the Placenta
    Leslie Myatt; Fiscal Year: 2012
    ....
  40. ERIC KIRK LAU; Fiscal Year: 2014
    ..abstract_text> ..
  41. Nanoelectrode arrays for study of the molecular mechanisms, triggers, and inhibit
    Peter J Burke; Fiscal Year: 2012
    ..A high throughput technology to monitor P in mitochondria will allow further studies of these issues in cancer biology. ..
  42. Targeting ATAP-mediated Apoptosis in Treatment of Prostate Cancer
    Zelin Sheng; Fiscal Year: 2013
    ....
  43. David W Kamp; Fiscal Year: 2016
    ..g. asbestos, cigarette smoke, air-borne particulate matter etc). ..
  44. The in vivo role of the mitochondrial p53 cell death program
    UTE MARTHA MOLL; Fiscal Year: 2013
    ..This is the thrust of this proposal. Furthermore, this proposal aims at gaining more mechanistic insight into how p53 works at the mitochondria to permeabilize these organelles. ..
  45. GM1 at the ER-mitochondrion microdomains regulates Ca2+ signaling and apoptosis
    ALESSANDRA D apos AZZO; Fiscal Year: 2010
    ..This knowledge is essential for designing new therapies for children with GM1-gangliosidosis and possibly those with other GSL storage diseases. ..
  46. Molecular Targeting of the Survivin Pathway in Cancer
    Dario C Altieri; Fiscal Year: 2010
    ..This work will provide a mechanistic foundation for the validation and further development of molecular antagonists of the survivin pathway for novel cancer therapeutics in humans. ..
  47. Bax function in apoptosis
    DONALD DAVID NEWMEYER; Fiscal Year: 2013
    ..We also want to understand how mutations of Opa1 that occur in patients with a disease called "Autosomal Dominant Optic Atrophy" can cause hereditary loss of vision later in life. ..
  48. Mitochrondrial Regulation of Apoptosis
    Tomomi Kuwana; Fiscal Year: 2013
    ..Mapping the distribution of Bax along the edge of the pores will enable us to determine whether Bax pores are mainly lipidic or proteinaceous. ..
  49. GM1 as apoptotic signal in neurodegenerative GM1-gangliosidosis
    ALESSANDRA D apos AZZO; Fiscal Year: 2010
    ..The proposed studies may also reveal basic biological processes controlled by the molecules that are accumulated in GM1. This knowledge is essential for designing new therapies for children with GM1 and possibly those with other LSDs. ..
  50. David W Kamp; Fiscal Year: 2016
    ..g. asbestos, cigarette smoke, particulate matter etc). ..
  51. Subcellular Regulation of Autophagic Flux in Cardiomyocytes and the Heart
    Roberta A Gottlieb; Fiscal Year: 2012
    ..Its role in the heart is poorly understood. Since infection and inflammation increase autophagy and exacerbate heart failure, we hypothesis that autophagy contributes to injury in this context. ..
  52. MAVS protein: A role of mitochondria in innate immunity and cardioprotection
    Kirk Peterson; Fiscal Year: 2013
    ..abstract_text> ..
  53. Mechanisms of Mutant SOD 1-Mediated Mitochondria Toxicity in the Spinal Cord of A
    Davide Trotti; Fiscal Year: 2012
    ..They play a pivotal role in maintaining neuronal cell alive. A pathology-driven impairment of these organelles may shift the balance between life and death and lead to neuronal degeneration. ..
  54. Atg6 in Protection Against Insulin Resistance
    NICHOLAS PERRY GREENE; Fiscal Year: 2012
    ..In these studies we will elucidate the role of mitochondrial stress-induced autophagy in the onset of insulin resistance. ..
  55. Astar Winoto; Fiscal Year: 2014
    ..abstract_text> ..
  56. Paul Dent; Fiscal Year: 2014
    ..As Lapatinib is already FDA approved, the successful completion of the studies proposed in this application would rapidly facilitate phase I translation of the drug combination in patients with recurrent breast cancer. ..
  57. Molecular mechanism of ADNF and ADNP peptides in prevention of mitochondrial dysf
    Youssef Sari; Fiscal Year: 2010
    ..This will provide information in finding therapeutic ways for the treatment of fetal alcohol exposure. ..
  58. Mitochondrial ion channels in hypoxic neurons
    Elizabeth Ann Jonas; Fiscal Year: 2013
    ..We hypothesize that in the setting of brain ischemia, such channel activity leads to cell death in the brain and that this death can be prevented by a pharmacological inhibitor of BCL-2-induced mitochondrial ion channels. ..
  59. GR SCOTT BUDINGER; Fiscal Year: 2015
    ..Our studies will allow us to predict whether these agents are likely to modulate the cardiovascular response to inhaled particles. ..
  60. Role of leukemia-associated protein MLF1 in apoptotic cell death
    ALAN ALI POURPAK; Fiscal Year: 2011
    ..Generation of an Npm-MLF1 mouse model of MDS/AML pathogenesis would serve as an experimental tool to assess the effectiveness of both existing as well as novel antileukemia therapies. ..
  61. Role of mitochondria in cardiac protection
    Peipei Ping; Fiscal Year: 2010
    ..These studies will provide novel and mechanistic information to aid our understanding of mitochondrial function in myocardial ischemic injury. ..
  62. ANIL KUMAR JAISWAL; Fiscal Year: 2014
    ..The studies may also provide the basis for further analysis of identified targets (cis- and trans-elements) that could ultimately allow us to increase the chemoprotective capacity of cells. ..
  63. Molecular Regulation of Erythroid Differentiation
    Min Chen; Fiscal Year: 2013
    ..The proposed studies may lead to better understanding of the pathogenesis of hemotological disorders associated with defective erythroid maturation. ..
  64. Prolactin as a Growth Factor in Breast Cancer
    Nira Ben-Jonathan; Fiscal Year: 2013
    ..The long term goal is to establish FDA-approved, long acting dopamine agonists as suppressor or PRL secretion, resulting in increased efficacy of chemotherapeutic agents in breast cancer patients. ..
  65. Cornelia M Weyand; Fiscal Year: 2016
    ..The studies will include vaccinating RA patients with an influenza vaccine to test whether they can build sufficient T cells to be protected from infection. ..
  66. Endocrine resistance in breast cancer
    ROBERT R CLARKE; Fiscal Year: 2013
    ..Aim 3: We will build and test interactive in silico models of how XBP1, RELA, ER, and BCL2 signal to affect breast cancer cell survival in the context of UPR and endocrine responsiveness. ..
  67. New Molecular and Cellular Mechanisms of Glaucoma
    Andrei Surguchov; Fiscal Year: 2013
    ..The purpose of this proposal is to examine how 3-synuclein affects prosurvival/prodeath signaling and how it is implicated in MMP-9 regulation in glaucoma. ..
  68. Bethany B Moore; Fiscal Year: 2016
    ..via which periostin and TGFb regulate each other and the function of lung mesenchymal cells Aim 4) To determine whether periostin levels in plasma or bronchoalveolar lavage fluid of IPF patients correlate with disease progression ..
  69. Lipidoid Nanoparticles with Simultaneous Multi-Gene Regulation for Cancer Therapy
    Yizhou Dong; Fiscal Year: 2013
    ..It is my hope that this platform will enable scientists in the future to fine-tune the combination of siRNA and pDNA for specific disease treatment in specific individuals, thereby advancing the field of personalized medicine. ..
  70. IRF1 regulation of BCL2 family members determines breast cancer cell fate
    JESSICA LEA ROBERTS; Fiscal Year: 2013
    ..The studies will also determine whether induction of IRF1 signaling can improve responsiveness to AEs when combined with a BCL2 inhibitor. ..
  71. W Mark Saltzman; Fiscal Year: 2016
    ..In all of our approaches, we rely on materials that are already acceptable to the FDA in clinical settings;therefore, our results in animal models will be ready for translation into clinical practice. ..
  72. Gyorgy Hajnoczky; Fiscal Year: 2016
    ..Tumors are commonly resistant to cell killing agents, and our work might show an Achilles'heel of hepatocarcinoma. ..
  73. CHRISTINE ANN CARTWRIGHT; Fiscal Year: 2015
    ..Exploitation of these multiple functions could be used to develop new and more powerful and selective strategies for treatment of human colon cancer. ..
  74. Zhenfeng Duan; Fiscal Year: 2014
    ..and cytotoxic drugs for maximum cell-kill effect. ..
  75. REBECCA I GOLDSTEIN; Fiscal Year: 2016
    ....
  76. Targeting BAX Oligomerization in Hematologic Disease
    Evripidis Gavathiotis; Fiscal Year: 2013
    ..abstract_text> ..
  77. Cell Models for Alzheimer's disease (AD): Lipids and Related Signaling Pathways
    Grace Y Sun; Fiscal Year: 2012
    ..These collaborative studies should identify novel strategies to control chronic inflammation and neurodegeneration in AD. ..
  78. David Kozono; Fiscal Year: 2016
    ..In so doing, I hope to provide rationale for testing proteasome and/or USP9X inhibition in Phase I/II trials, and to identify biomarkers for patient selection. ..
  79. Rheem D Medh; Fiscal Year: 2015
    ..Studies proposed here will unravel the complex pathways that govern leukemic cell proliferation, differentiation and apoptosis so that more effective therapeutic strategies may be developed. ..
  80. Anthony G Letai; Fiscal Year: 2016
    ..Moreover, using in vitro co-culture systems, we will study the efficacy and mechanisms of drugs intended to interrupt CLL interactions with stromal cells. Our goal is to identify which CLL patients will most benefit from such therapies. ..
  81. Antibody directed delivery of short interfering RNA for the treatment of ovarian
    Maria Corinna Palanca-Wessels; Fiscal Year: 2013
    ..Additionally, she will utilize the outstanding resources offered by both the Fred Hutchinson Cancer Research Center and the University of Washington to foster her career development. ..
  82. JACQUES EDUARDO NOR; Fiscal Year: 2015
    ..Our research team is fully committed to the development of a mechanism- based therapy that will enhance the survival and quality of life of patients with adenoid cystic carcinoma. ..
  83. Role of B-cell oncogenes and microRNA-34 in B-lymphopoiesis and neoplasia
    Dinesh S Rao; Fiscal Year: 2013
    ..Hence, these studies have a direct relevance to public health and most importantly, to patients living with these diseases. ..
  84. James W Rocco; Fiscal Year: 2015
    ..It thus will support development of intensified treatments for those at high risk and of treatments with less morbidity for those at low risk. ..
  85. GARY I YELLEN; Fiscal Year: 2016
    ..Understanding this pathway should yield valuable clues for translating this potent anticonvulsant effect of metabolism into improved therapies for the many individuals with intractable epilepsy. ..
  86. NLRP1 activation induces deletion of hematopoietic progenitor cells
    BEN ADAM CROKER; Fiscal Year: 2013
    ..C. characterise the role of NLRP1 in hematopoietic stem and progenitor cells during hematopoietic stress induced by infection and chemotherapy, to understand beneficial and pathological roles for NLRP1 activation ..
  87. Chunhong Yan; Fiscal Year: 2014
    ....
  88. Craig M Coopersmith; Fiscal Year: 2016
    ..Understanding how sepsis- induced gut apoptosis alters overall intestinal integrity may therefore have significant therapeutic implications in a disease that is the most common killer in intensive care units. ..
  89. CLARE MARIE ADAMS; Fiscal Year: 2014
    ..The education, training, and career development program outlined in this proposal will support my goal of becoming an independent investigator in cancer biology. ! ..
  90. Suzanne C Hoppins; Fiscal Year: 2015
    ..abstract_text> ..
  91. Bcl-2 selective inhibitors: development and application to cancer treatment
    Chengguo Xing; Fiscal Year: 2009
    ....
  92. Bcl-2, A Key Factor for Dentinogenesis and Tooth Damage Repair
    Wenjian Zhang; Fiscal Year: 2010
    ..It is expected to generate new interventions to preserving the vitality and functions of teeth injured by infections or trauma, and contributing to fabricated teeth via bioengineering. ..
  93. Bc12 regulates osteoclast survival
    Junro Yamashita; Fiscal Year: 2010
    ..Bcl2 could be a therapeutic target to suppress osteoclasts. This project will clarify the Bcl2 regulation of osteoclastogenesis via osteoclast progenitors. ..
  94. Molecular Adaptation of Hypoxia in Oxygen Sensing Cells
    David Millhorn; Fiscal Year: 2007
    ..This information may be helpful for developing strategies and targets for treating hypoxia-associated diseases and injury. ..
  95. The BCL-2 Homologues of Gamma Herpesviruses
    J Marie Hardwick; Fiscal Year: 2006
    ..In Aim 3, the expression patterns of BHRF1 and BALF1 during virus infections will be explored by inserting tags into the their reading frames within the Epstein-Barr virus genome. ..
  96. BC1-2 REARRANGEMENTS IN CLL
    Louise Showe; Fiscal Year: 1992
    ..These studies can help to define the molecular basis of the pathogenesis of CLL...
  97. Transport and Insertion of Outer Membrane Proteins
    Sangita Sinha; Fiscal Year: 2009
    ..This application aims to investigate atomic details of the mechanism by which 3-herpesviruses inhibit autophagy, providing a better understanding of 3-herpesviral pathogenicity. ..