Bcl-xL

Summary

Gene Symbol: Bcl-xL
Description: BCL2 like 1
Alias: BCL-XL/S, BCL2L, BCLX, Bcl-X, PPP1R52, bcl-2-like protein 1, apoptosis regulator Bcl-X, protein phosphatase 1, regulatory subunit 52
Species: human

Top Publications

  1. pmc ERK1/2-dependent phosphorylation of BimEL promotes its rapid dissociation from Mcl-1 and Bcl-xL
    Katherine E Ewings
    Laboratory of Molecular Signalling, The Babraham Institute, Babraham Research Campus, Cambridge, UK
    EMBO J 26:2856-67. 2007
  2. doi Lactate dehydrogenase 5 expression in melanoma increases with disease progression and is associated with expression of Bcl-XL and Mcl-1, but not Bcl-2 proteins
    Liqing Zhuang
    Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
    Mod Pathol 23:45-53. 2010
  3. pmc Bcl-x(L) and Myeloid cell leukaemia-1 contribute to apoptosis resistance of colorectal cancer cells
    Henning Schulze-Bergkamen
    First Department of Medicine, Johannes Gutenberg University Mainz, Mainz, Germany
    World J Gastroenterol 14:3829-40. 2008
  4. pmc Insulin-like growth factor 1 receptor antibody induces rhabdomyosarcoma cell death via a process involving AKT and Bcl-x(L)
    L H Mayeenuddin
    Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892 4265, USA
    Oncogene 29:6367-77. 2010
  5. ncbi Heat shock factor 1 attenuates 4-Hydroxynonenal-mediated apoptosis: critical role for heat shock protein 70 induction and stabilization of Bcl-XL
    Aaron T Jacobs
    Department of Biochemistry, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt Ingram Comprehensive Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    J Biol Chem 282:33412-20. 2007
  6. pmc Siva-1 binds to and inhibits BCL-X(L)-mediated protection against UV radiation-induced apoptosis
    Li Xue
    Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:6925-30. 2002
  7. pmc DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl-XL and induction of autophagy
    Einat Zalckvar
    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel
    EMBO Rep 10:285-92. 2009
  8. ncbi Distinct promoters mediate constitutive and inducible Bcl-XL expression in malignant lymphocytes
    F Habens
    Cancer Research UK Clinical Centre, Cancer Sciences Division, University of Southampton School of Medicine, Southampton General Hospital, Southampton, UK
    Oncogene 26:1910-9. 2007
  9. pmc Bcl-x(L) prevents the initial decrease in mitochondrial membrane potential and subsequent reactive oxygen species production during tumor necrosis factor alpha-induced apoptosis
    E Gottlieb
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Mol Cell Biol 20:5680-9. 2000
  10. ncbi T cell apoptosis causes peripheral T cell depletion in mice transgenic for the HIV-1 vpr gene
    J Yasuda
    Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato ku, Tokyo, 108 8639, Japan
    Virology 285:181-92. 2001

Research Grants

  1. NIH Director's Pioneer Award
    Junying Yuan; Fiscal Year: 2009
  2. J Marie Hardwick; Fiscal Year: 2014
  3. Mcl-1 as an essential regulator of cardiac mitochondrial function
    Asa B Gustafsson; Fiscal Year: 2013
  4. Junxuan Lu; Fiscal Year: 2014
  5. Junichi Sadoshima; Fiscal Year: 2016
  6. Apoptosis Control by Bcl-2 Family Members
    Craig B Thompson; Fiscal Year: 2012
  7. Vesna Jevtovic-Todorovic; Fiscal Year: 2014
  8. Heat Shock-Induced Apoptosis
    Shawn B Bratton; Fiscal Year: 2012
  9. NLR Family Proteins: Mechanisms and Regulation
    John C Reed; Fiscal Year: 2012
  10. J Kevin Foskett; Fiscal Year: 2016

Detail Information

Publications251 found, 100 shown here

  1. pmc ERK1/2-dependent phosphorylation of BimEL promotes its rapid dissociation from Mcl-1 and Bcl-xL
    Katherine E Ewings
    Laboratory of Molecular Signalling, The Babraham Institute, Babraham Research Campus, Cambridge, UK
    EMBO J 26:2856-67. 2007
    ..These results provide new insights into the role of Bim in cell death and its regulation by the ERK1/2 survival pathway...
  2. doi Lactate dehydrogenase 5 expression in melanoma increases with disease progression and is associated with expression of Bcl-XL and Mcl-1, but not Bcl-2 proteins
    Liqing Zhuang
    Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
    Mod Pathol 23:45-53. 2010
    ..The strong correlation of LDH-5 expression with Mcl-1 expression suggests that treatment strategies inhibiting the activity of Mcl-1 in melanoma patients should be investigated...
  3. pmc Bcl-x(L) and Myeloid cell leukaemia-1 contribute to apoptosis resistance of colorectal cancer cells
    Henning Schulze-Bergkamen
    First Department of Medicine, Johannes Gutenberg University Mainz, Mainz, Germany
    World J Gastroenterol 14:3829-40. 2008
    ..To explore the role of Bcl-x(L) and Myeloid cell leukaemia (Mcl)-1 for the apoptosis resistance of colorectal carcinoma (CRC) cells towards current treatment modalities...
  4. pmc Insulin-like growth factor 1 receptor antibody induces rhabdomyosarcoma cell death via a process involving AKT and Bcl-x(L)
    L H Mayeenuddin
    Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892 4265, USA
    Oncogene 29:6367-77. 2010
    ....
  5. ncbi Heat shock factor 1 attenuates 4-Hydroxynonenal-mediated apoptosis: critical role for heat shock protein 70 induction and stabilization of Bcl-XL
    Aaron T Jacobs
    Department of Biochemistry, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt Ingram Comprehensive Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    J Biol Chem 282:33412-20. 2007
    ..Overall, activation of HSF1 and stabilization of Bcl-X(L) mediate a protective response that may contribute significantly to the cellular biology of lipid peroxidation...
  6. pmc Siva-1 binds to and inhibits BCL-X(L)-mediated protection against UV radiation-induced apoptosis
    Li Xue
    Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:6925-30. 2002
    ..Natural complexes of Siva-1/BCL-X(L) are detected in HUT78 and murine thymocyte, suggesting a potential role for Siva-1 in regulating T cell homeostasis...
  7. pmc DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl-XL and induction of autophagy
    Einat Zalckvar
    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel
    EMBO Rep 10:285-92. 2009
    ....
  8. ncbi Distinct promoters mediate constitutive and inducible Bcl-XL expression in malignant lymphocytes
    F Habens
    Cancer Research UK Clinical Centre, Cancer Sciences Division, University of Southampton School of Medicine, Southampton General Hospital, Southampton, UK
    Oncogene 26:1910-9. 2007
    ....
  9. pmc Bcl-x(L) prevents the initial decrease in mitochondrial membrane potential and subsequent reactive oxygen species production during tumor necrosis factor alpha-induced apoptosis
    E Gottlieb
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Mol Cell Biol 20:5680-9. 2000
    ..These data suggest that Bcl-x(L) plays a regulatory role in controlling the membrane potential of and ROS production by mitochondria rather than acting as a direct antioxidant...
  10. ncbi T cell apoptosis causes peripheral T cell depletion in mice transgenic for the HIV-1 vpr gene
    J Yasuda
    Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato ku, Tokyo, 108 8639, Japan
    Virology 285:181-92. 2001
    ..Involvement of Bcl-x, Bax, and Caspase-1, but not of the Fas-Fas ligand system, was suggested in the apoptotic processes. These observations suggest that Vpr is involved in the pathogenesis of T cell depletion in HIV-infected people...
  11. pmc Development of a human neuronal cell model for human immunodeficiency virus (HIV)-infected macrophage-induced neurotoxicity: apoptosis induced by HIV type 1 primary isolates and evidence for involvement of the Bcl-2/Bcl-xL-sensitive intrinsic apoptosis pa
    Wei Chen
    Department of Neurology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA
    J Virol 76:9407-19. 2002
    ..Modulation of bcl-2 gene expression may therefore offer adjunctive neuroprotection against development of AIDS dementia...
  12. pmc Vesicular stomatitis virus induces apoptosis primarily through Bak rather than Bax by inactivating Mcl-1 and Bcl-XL
    Alicia F Pearce
    Department of Biochemistry, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    J Virol 83:9102-12. 2009
    ..Similarly, treatment with an inhibitor of caspase-8 inhibited VSV-induced apoptosis. These results indicate a role for cross talk from the death receptor pathway in the activation of the mitochondrial pathway by VSV...
  13. pmc Apoptosis blocks Beclin 1-dependent autophagosome synthesis: an effect rescued by Bcl-xL
    S Luo
    Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust MRC Building, Hills Road, Cambridge, CB2 0XY, UK
    Cell Death Differ 17:268-77. 2010
    ..The cleavage of Beclin 1 is a critical event whereby caspases inhibit autophagy, as a non-cleavable Beclin 1 mutant restored autophagy in cells overexpressing Bax...
  14. pmc Endogenous Bak inhibitors Mcl-1 and Bcl-xL: differential impact on TRAIL resistance in Bax-deficient carcinoma
    Bernhard Gillissen
    Department of Hematology, Oncology, and Tumor Immunology, University Medical Center Charite, Humboldt University, 13125 Berlin, Germany
    J Cell Biol 188:851-62. 2010
    ....
  15. 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...
  16. ncbi Bcl-x(L) complements Saccharomyces cerevisiae genes that facilitate the switch from glycolytic to oxidative metabolism
    Matthew G Vander Heiden
    Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA
    J Biol Chem 277:44870-6. 2002
    ..Further characterization of the genes identified in this screen may enhance our understanding of Bcl-x(L) function in mammalian cells, and of cell survival pathways in general...
  17. 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...
  18. ncbi Membrane-insertion fragments of Bcl-xL, Bax, and Bid
    Ana J García-Sáez
    Departament de Bioquimica i Biologia Molecular, Universitat de Valencia, Spain
    Biochemistry 43:10930-43. 2004
    ..Thus, the above fragments should be considered for the definition of plausible models of the active, membrane-bound species of Bcl-2 proteins...
  19. pmc Bax activation by engagement with, then release from, the BH3 binding site of Bcl-xL
    F Gautier
    Centre de Recherche en Cancérologie Nantes Angers UMR 892 INSERM Université de Nantes, Institut de Recherche Thérapeutique de l Université de Nantes, Nantes, France
    Mol Cell Biol 31:832-44. 2011
    ..This mechanism might contribute to the clinical efficiency of Bcl-x(L) inhibitors...
  20. ncbi Bax inhibitor-1, a mammalian apoptosis suppressor identified by functional screening in yeast
    Q Xu
    Burnham Institute Program on Apoptosis and Cell Death Research La Jolla, California 92037, USA
    Mol Cell 1:337-46. 1998
    ..Conversely, BI-1 antisense induced apoptosis. BI-1 thus represents a new type of regulator of cell death pathways controlled by Bcl-2 and Bax...
  21. ncbi Interaction of Alzheimer's presenilin-1 and presenilin-2 with Bcl-X(L). A potential role in modulating the threshold of cell death
    B J Passer
    T Cell Apoptosis Unit, Laboratory of Cellular and Molecular Immunology, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 274:24007-13. 1999
    ..Together, these data support a possible role of the Alzheimer's presenilins in modulating the anti-apoptotic effects of Bcl-X(L)...
  22. ncbi The HIV-1 vpr protein induces anoikis-resistance by modulating cell adhesion process and microfilament system assembly
    P Matarrese
    Department of Ultrastructures, Instituto Superiore di Sanita, Viale Regina Elena, 299 00161 Rome, Italy
    Cell Death Differ 7:25-36. 2000
    ..e. by inducing anoikis-resistance. These particular effects of vpr might enhance the homing, spreading and survival of the infected lymphocytes, thus contributing to virus persistence in the course of acute HIV-1 infection...
  23. ncbi Aven, a novel inhibitor of caspase activation, binds Bcl-xL and Apaf-1
    B N Chau
    Department of Pharmacology and Molecular Sciences, Johns Hopkins University, Schools of Medicine and Public Health, Baltimore, Maryland 21205, USA
    Mol Cell 6:31-40. 2000
    ..Consistent with this idea, Aven inhibited the proteolytic activation of caspases in a cell-free extract and suppressed apoptosis induced by Apaf-1 plus caspase-9. Thus, Aven represents a new class of cell death regulator...
  24. ncbi MAP-1, a novel proapoptotic protein containing a BH3-like motif that associates with Bax through its Bcl-2 homology domains
    K O Tan
    Institute of Molecular and Cell Biology, 30 Medical Dr, Singapore 117609, Republic of Singapore
    J Biol Chem 276:2802-7. 2001
    ..These data suggest that MAP-1 mediates apoptosis through a mechanism that involves binding to Bax...
  25. ncbi Apoptosis enhancement by the HIV-1 Nef protein
    A Rasola
    Division of Molecular Oncology, Institute for Cancer Research, University of Torino Medical School, Candiolo, Italy
    J Immunol 166:81-8. 2001
    ..These data show that Nef enhances programmed cell death in different cell types by affecting multiple critical components of the apoptotic machinery independently from the Fas pathway...
  26. pmc The human immunodeficiency virus type 1 accessory protein Vpu induces apoptosis by suppressing the nuclear factor kappaB-dependent expression of antiapoptotic factors
    H Akari
    Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 194:1299-311. 2001
    ..Thus, Vpu induces apoptosis through activation of the caspase pathway by way of inhibiting the NF-kappaB-dependent expression of antiapoptotic genes...
  27. ncbi De novo ceramide regulates the alternative splicing of caspase 9 and Bcl-x in A549 lung adenocarcinoma cells. Dependence on protein phosphatase-1
    Charles E Chalfant
    Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA
    J Biol Chem 277:12587-95. 2002
    ..This is the first report on the dynamic regulation of RNA splicing of members of the Bcl-2 and caspase families in response to regulators of apoptosis...
  28. ncbi Survival function of protein kinase C{iota} as a novel nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-activated bad kinase
    Zhaohui Jin
    University of Florida Shands Cancer Center, Department of Medicine, University of Florida, Gainesville, Florida 32610 0232, USA
    J Biol Chem 280:16045-52. 2005
    ....
  29. ncbi Rapamycin induces apoptosis of JN-DSRCT-1 cells by increasing the Bax : Bcl-xL ratio through concurrent mechanisms dependent and independent of its mTOR inhibitory activity
    Oscar M Tirado
    Laboratory of Experimental Carcinogenesis, Department of Radiation Medicine, Georgetown University Medical Center, Washington, DC, USA
    Oncogene 24:3348-57. 2005
    ..Furthermore, these results strongly support the introduction of the use of rapamycin as a cytotoxic agent for the treatment of DSRCT...
  30. ncbi SAP155 Binds to ceramide-responsive RNA cis-element 1 and regulates the alternative 5' splice site selection of Bcl-x pre-mRNA
    Autumn Massiello
    Department of Biochemistry, Rm 2 016, Sanger Hall, Virginia Commonwealth University, 1101 East Marshall St, P O Box 980614, Richmond, Virginia 23298 0614, USA
    FASEB J 20:1680-2. 2006
    ....
  31. ncbi Mcl-1, Bcl-XL and Stat3 expression are associated with progression of melanoma whereas Bcl-2, AP-2 and MITF levels decrease during progression of melanoma
    Liqing Zhuang
    Discipline of Pathology, Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia
    Mod Pathol 20:416-26. 2007
    ..These findings have important implications for the development of treatments targeting antiapoptotic proteins in patients with melanoma...
  32. ncbi Significant coexpression of GLUT-1, Bcl-xL, and Bax in colorectal cancer
    Andrzej Wincewicz
    Departments of General and Clinical Pathomorphology, Medical University of Bialystok, Waszyngtona St 13, 15 269 Bialystok, Poland
    Ann N Y Acad Sci 1095:53-61. 2007
    ....
  33. pmc BI-1 regulates endoplasmic reticulum Ca2+ homeostasis downstream of Bcl-2 family proteins
    Chunyan Xu
    Program on Apoptosis and Cell Death Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Biol Chem 283:11477-84. 2008
    ..The findings reveal a hierarchy of functional interactions of BI-1 with Bcl-2/Bax family proteins in regulating ER Ca(2+) homeostasis...
  34. doi EGL-1 BH3 mutants reveal the importance of protein levels and target affinity for cell-killing potency
    E F Lee
    The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
    Cell Death Differ 15:1609-18. 2008
    ..These results demonstrate how levels of BH3-only proteins, target affinity and the spectrum of neutralization of pro-survival proteins all contribute to killing activity...
  35. pmc BCL-xL is a target gene regulated by hypoxia-inducible factor-1{alpha}
    Ni Chen
    Laboratory of Pathology, Departments of Pathology and Urology, and Laboratory of Stem Cell Research, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China 610041
    J Biol Chem 284:10004-12. 2009
    ..HIF-1alpha-dependent BCL-xL overexpression may be an important mechanism by which HIF-1alpha protects prostate cancer cells from apoptosis and leads to treatment resistance...
  36. 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...
  37. 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...
  38. pmc Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria
    M Narita
    Department of Medical Genetics, Biomedical Research Center, Osaka University Medical School, 2 2 Yamadaoka, Suita, Osaka 565 0871, Japan
    Proc Natl Acad Sci U S A 95:14681-6. 1998
    ..Taken together, these findings suggest that proapoptotic Bcl-2 family proteins, including Bax and Bak, induce the mitochondrial PT and cytochrome c release by interacting with the PT pores...
  39. 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...
  40. pmc Rationale for Bcl-xL/Bad peptide complex formation from structure, mutagenesis, and biophysical studies
    A M Petros
    Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Illinois 60064 6098, USA
    Protein Sci 9:2528-34. 2000
    ..Both peptides showed an increase in helix propensity compared to the wild-type and exhibited an enhanced affinity for Bcl-xL...
  41. ncbi BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes
    Philippe Bouillet
    The Walter and Eliza Hall Institute of Medical Research, Melbourne, P O The Royal Melbourne Hospital, Victoria 3050, Australia
    Nature 415:922-6. 2002
    ..TCR ligation upregulated Bim expression and promoted interaction of Bim with Bcl-XL, inhibiting its survival function. These findings identify Bim as an essential initiator of apoptosis in thymocyte-negative selection...
  42. ncbi Inhibition of apoptosis in human breast cancer cells: role in tumor progression to the metastatic state
    Yolanda Fernandez
    Centro de Oncologia Molecular, Institut de Recerca Oncològica I R O, Ciutat Sanitària i Universitària de Bellvitge C S U B, Barcelona, Spain
    Int J Cancer 101:317-26. 2002
    ..These genes increase tumor metastasis when the oncogenic background has triggered the metastatic process, in which anoikis might determine tumor progression when the life span of the cells is extended...
  43. pmc Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation
    Deepak Nijhawan
    Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
    Genes Dev 17:1475-86. 2003
    ..The disappearance of Mcl-1 is also required for other mitochondrial apoptotic events including Bax translocation, cytochrome c release, and caspase activation...
  44. pmc Bcl-x(L) sequesters its C-terminal membrane anchor in soluble, cytosolic homodimers
    Seon Yong Jeong
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892 1414, USA
    EMBO J 23:2146-55. 2004
    ..The C-terminal tail of Bcl-x(L) is also required to mediate Bcl-x(L)/Bax heterodimer formation. Both mitochondrial import and antiapoptotic activity of different Bcl-x(L) mutants correlate with their ability to form homodimers...
  45. 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...
  46. ncbi Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak
    Simon N Willis
    Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
    Science 315:856-9. 2007
    ..Our results indicate that BH3-only proteins induce apoptosis at least primarily by engaging the multiple pro-survival relatives guarding Bax and Bak...
  47. pmc Protein isoaspartate methyltransferase prevents apoptosis induced by oxidative stress in endothelial cells: role of Bcl-Xl deamidation and methylation
    Amelia Cimmino
    Department of Biochemistry and Biophysics, School of Medicine and Surgery, Second University of Naples, Naples, Italy
    PLoS ONE 3:e3258. 2008
    ..Previous evidence supports a role of protein deamidation in the acquisition of susceptibility to apoptosis. Aim of this work was to shed a light on the role of PCMT in apoptosis clarifying the relevant mechanism(s)...
  48. ncbi Bcl-XL protein is markedly decreased in UVB-irradiated basal cell carcinoma cell lines through proteasome-mediated degradation
    Kun Park
    Department of Dermatology, Eulji Hospital, Seoul 139 711, Korea
    Oncol Rep 21:689-92. 2009
    ....
  49. pmc Differential dependence on Beclin 1 for the regulation of pro-survival autophagy by Bcl-2 and Bcl-xL in HCT116 colorectal cancer cells
    Muriel Priault
    CNRS IBGC UMR 5095, Bordeaux, France
    PLoS ONE 5:e8755. 2010
    ....
  50. 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...
  51. pmc Bcl-x(L) retrotranslocates Bax from the mitochondria into the cytosol
    Frank Edlich
    Surgical Neurology Branch, NINDS, National Institutes of Health, Bethesda, MD 20892, USA
    Cell 145:104-16. 2011
    ..We propose that Bcl-x(L) inhibits and maintains Bax in the cytosol by constant retrotranslocation of mitochondrial Bax...
  52. doi BCL2L1 has a functional role in colorectal cancer and its protein expression is associated with chromosome 20q gain
    Anke H Sillars-Hardebol
    Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
    J Pathol 226:442-50. 2012
    ..Therefore, even though BCL2L1 affects CRC biology in a 20q gain-dependent manner, it is not likely to be a driver of chromosome 20q gain associated adenoma-to-carcinoma progression...
  53. pmc Multiple Bcl-2 family members demonstrate selective dimerizations with Bax
    T W Sedlak
    Department of Medicine and Pathology, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 92:7834-8. 1995
    ..This suggests that the susceptibility to apoptosis is determined by multiple competing dimerizations in which Bax may be a common partner...
  54. ncbi Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death
    E Yang
    Howard Hughes Medical Institute, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110
    Cell 80:285-91. 1995
    ..The susceptibility of a cell to a death signal is determined by these competing dimerizations in which levels of Bad influence the effectiveness of Bcl-2 versus Bcl-xL in repressing death...
  55. ncbi bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death
    L H Boise
    Howard Hughes Medical Institute, Department of Medicine, University of Chicago, Illinois 60637
    Cell 74:597-608. 1993
    ..In contrast, bcl-xL is found in tissues containing long-lived postmitotic cells, such as adult brain. Together these data suggest that bcl-x plays an important role in both positive and negative regulation of programmed cell death...
  56. ncbi Bax-independent inhibition of apoptosis by Bcl-XL
    E H Cheng
    Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland 21287 7681, USA
    Nature 379:554-6. 1996
    ..Specific mutations that disrupt the ability of Bcl-XL to interact with Bax or Bak still preserve 70-80% of the anti-death activity of wild-type Bcl-XL...
  57. ncbi X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death
    S W Muchmore
    Protein Crystallography, Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    Nature 381:335-41. 1996
    ..The structural similarity may provide a clue to the mechanism of action of the Bcl-2 family of proteins...
  58. ncbi Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis
    M Sattler
    Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, IL 60064, USA
    Science 275:983-6. 1997
    ..Mutations in full-length Bak that disrupt either type of interaction inhibit the ability of Bak to heterodimerize with Bcl-xL...
  59. pmc p28 Bap31, a Bcl-2/Bcl-XL- and procaspase-8-associated protein in the endoplasmic reticulum
    F W Ng
    Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, Quebec, Canada H3G 1Y6
    J Cell Biol 139:327-38. 1997
    ..This raises the possibility that the p28 complex contributes to the regulation of procaspase-8 or a related caspase in response to E1A, dependent on the status of the Bcl-2 setpoint within the complex...
  60. ncbi Bcl-xL regulates the membrane potential and volume homeostasis of mitochondria
    M G Vander Heiden
    Gwen Knapp Center and Committee on Immunology, Department of Medicine, University of Chicago, Illinois 60637, USA
    Cell 91:627-37. 1997
    ..These data suggest that Bcl-xL promotes cell survival by regulating the electrical and osmotic homeostasis of mitochondria...
  61. pmc Bim: a novel member of the Bcl-2 family that promotes apoptosis
    L O'Connor
    The Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Victoria, Australia
    EMBO J 17:384-95. 1998
    ..Hence, Bim appears to act as a 'death ligand' which can only neutralize certain members of the pro-survival Bcl-2 sub-family...
  62. pmc Modulation of cell death by Bcl-XL through caspase interaction
    R J Clem
    Department of Molecular Microbiology and Immunology, Johns Hopkins University Schools of Public Health and Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 95:554-9. 1998
    ....
  63. ncbi Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex
    G Pan
    Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    J Biol Chem 273:5841-5. 1998
    ..Consistent with a central role for caspase-9, a dominant negative form effectively inhibited cell death initiated by a wide variety of inducers...
  64. pmc Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation
    Y Hu
    Departments of Pathology and Comprehensive Cancer Center, 1500 East Medical Center Drive, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Proc Natl Acad Sci U S A 95:4386-91. 1998
    ..These experiments demonstrate that Bcl-XL associates with caspase-9 and Apaf-1, and show that Bcl-XL inhibits the maturation of caspase-9 mediated by Apaf-1, a process that is evolutionarily conserved from nematodes to humans...
  65. pmc Mutagenesis of the BH3 domain of BAX identifies residues critical for dimerization and killing
    K Wang
    Departments of Medicine and Pathology, Division of Molecular Oncology, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Mol Cell Biol 18:6083-9. 1998
    ..These data are consistent with a model in which BAX death agonist activity may require an intramembranous conformation of this molecule that is not assessed accurately by classic binding assays...
  66. pmc Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein
    X H Liang
    Departments of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Virol 72:8586-96. 1998
    ..These findings demonstrate that Beclin is a novel Bcl-2-interacting cellular protein that may play a role in antiviral host defense...
  67. ncbi Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC
    S Shimizu
    Osaka University Medical School, Biomedical Research Center, Department of Medical Genetics, Suita, Japan
    Nature 399:483-7. 1999
    ..Our results indicate that the Bcl-2 family of proteins bind to the VDAC in order to regulate the mitochondrial membrane potential and the release of cytochrome c during apoptosis...
  68. ncbi Human homologue of S. pombe Rad9 interacts with BCL-2/BCL-xL and promotes apoptosis
    K Komatsu
    Drug Discovery Program, H Lee Moffitt Cancer Center and Research Institute, Department of Pharmacology and Therapeutics, University of South Florida College of Medicine, 12902 Magnolia Drive, Tampa, Florida 33612, USA
    Nat Cell Biol 2:1-6. 2000
    ..These findings indicate that RAD9 may have a new role in regulating apoptosis after DNA damage, in addition to its previously described checkpoint-control and other radioresistance-promoting functions...
  69. ncbi PUMA induces the rapid apoptosis of colorectal cancer cells
    J Yu
    The Johns Hopkins Oncology Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA
    Mol Cell 7:673-82. 2001
    ..Based on its unique expression patterns, p53 dependence, and biochemical properties, PUMA may be a direct mediator of p53-associated apoptosis...
  70. ncbi PUMA, a novel proapoptotic gene, is induced by p53
    K Nakano
    Regulation of Cell Growth Laboratory, National Cancer Institute at Frederick, Maryland 21702, USA
    Mol Cell 7:683-94. 2001
    ..Antisense inhibition of PUMA expression reduced the apoptotic response to p53, and PUMA is likely to play a role in mediating p53-induced cell death through the cytochrome c/Apaf-1-dependent pathway...
  71. ncbi BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis
    E H Cheng
    Howard Hughes Medical Institute, Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Mol Cell 8:705-11. 2001
    ..Thus, in mammals, BH3 domain-only molecules activate multidomain proapoptotic members to trigger a mitochondrial pathway, which both releases cytochrome c to activate caspases and initiates caspase-independent mitochondrial dysfunction...
  72. pmc c-Abl tyrosine kinase regulates the human Rad9 checkpoint protein in response to DNA damage
    Kiyotsugu Yoshida
    Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 22:3292-300. 2002
    ..These findings indicate that Rad9 is regulated by a c-Abl-dependent mechanism in the apoptotic response to genotoxic stress...
  73. ncbi Ionomycin-activated calpain triggers apoptosis. A probable role for Bcl-2 family members
    Shirley Gil-Parrado
    Abteilung für Klinische Chemie und Klinische Biochemie, Chirurgische Klinik Innenstadt, Klinikum der LMU München, Nussbaumstrasse 20, D 80336 Munich, Germany
    J Biol Chem 277:27217-26. 2002
    ..We conclude that ionomycin-induced calpain activation promotes decrease of Bcl-2 proteins thereby triggering the intrinsic apoptotic pathway...
  74. ncbi Bcl-xL deamidation is a critical switch in the regulation of the response to DNA damage
    Benjamin E Deverman
    Division of Urology, Department of Cell Biology and Physiology, School of Medicine, Washington University, 660 South Euclid Avenue, Campus Box 8052, Saint Louis, MO 63110, USA
    Cell 111:51-62. 2002
    ..Our results suggest that the regulation of Bcl-xL deamidation has a critical role in the tumor-specific activity of DNA-damaging antineoplastic agents...
  75. ncbi Cellular response to an antisense-mediated shift of Bcl-x pre-mRNA splicing and antineoplastic agents
    Danielle R Mercatante
    UNC Lineberger Comprehensive Cancer Center and Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 7295, USA
    J Biol Chem 277:49374-82. 2002
    ..Treatment with 5'Bcl-x AS may enhance the efficacy of standard anti-cancer regimens and should be explored, especially in recurrent prostate cancer...
  76. ncbi p53 has a direct apoptogenic role at the mitochondria
    Motohiro Mihara
    Department of Pathology, Stony Brook University, Stony Brook, NY 11794, USA
    Mol Cell 11:577-90. 2003
    ..This opens the possibility that mutations might represent "double-hits" by abrogating the transcriptional and mitochondrial apoptotic activity of p53...
  77. 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...
  78. pmc Induction of cell death by the BH3-only Bcl-2 homolog Nbk/Bik is mediated by an entirely Bax-dependent mitochondrial pathway
    Bernhard Gillissen
    Department of Hematology, Charité Campus Berlin Buch, Humboldt University, D 13125 Berlin Buch, Germany
    EMBO J 22:3580-90. 2003
    ..Since, in addition, Nbk did not localize to the mitochondria, our data suggest a model in which Nbk acts as an indirect killer to trigger Bax-dependent apoptosis, whereas Bak is not sufficient to confer sensitivity to Nbk...
  79. ncbi Prognostic significance of bcl-xL gene expression and apoptotic cell counts in follicular lymphoma
    Wei Li Zhao
    ERM 0220, Institut Universitaire d Hematologie, Universite Paris VII, Hopital Saint Louis, 1 avenue Claude Vellefaux, 75475 Paris Cedex 10, France
    Blood 103:695-7. 2004
    ..0235). Moreover, bcl-xL gene overexpression was linked to short overall survival times (P =.0129). The value of bcl-xL gene expression as a prognostic marker in follicular lymphoma should thus be considered...
  80. ncbi Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3
    Bingzhen Lin
    The Burnham Institute, Cancer Center, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell 116:527-40. 2004
    ....
  81. ncbi Bcl-x L blocks mitochondrial multiple conductance channel activation and inhibits 6-OHDA-induced death in SH-SY5Y cells
    Joaquin Jordan
    Centro Regional de Investigaciones Biomédicas, Universidad de Castilla La Mancha, Albacete, Spain
    J Neurochem 89:124-33. 2004
    ....
  82. ncbi Prognostic significance of Bcl-xL in human hepatocellular carcinoma
    Jota Watanabe
    Department of Surgery, Ehime University School of Medicine, Onsen gun, Japan
    Surgery 135:604-12. 2004
    ..We investigated the correlation between overexpression of Bcl-xL, an anti-apoptosis-related protein of the Bcl-2 family, and the clinical course of hepatocellular carcinoma (HCC)...
  83. ncbi Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in Jurkat leukemia T cells
    Changjiang Weng
    Center for Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China 100080
    J Biol Chem 280:10491-500. 2005
    ..These results suggested that removal of N-terminal domains of Bid by caspase-8 and Mcl-1 by caspase-3 enabled the maximal mitochondrial perturbation that potentiated TRAIL-induced apoptosis...
  84. ncbi Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function
    Lin Chen
    The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville Victoria 3050, Australia
    Mol Cell 17:393-403. 2005
    ..The results suggest that apoptosis relies on selective interactions between particular subsets of these proteins and that it should be feasible to discover BH3-mimetic drugs that inactivate specific prosurvival targets...
  85. ncbi BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly
    Tomomi Kuwana
    La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA
    Mol Cell 17:525-35. 2005
    ..In this model, the simple inhibition of antiapoptotic functions is insufficient to induce apoptosis unless a direct activator of Bax or Bak is present...
  86. 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...
  87. ncbi Evidence that Ser87 of BimEL is phosphorylated by Akt and regulates BimEL apoptotic function
    Xiao Jun Qi
    Department of Cell Biology, Cleveland Clinic Lerner College of Medicine, Cleveland Clinic Foundation, OH 44195, USA
    J Biol Chem 281:813-23. 2006
    ..We propose that Ser(87) of Bim(EL) is an important regulatory site that is targeted by Akt to attenuate the pro-apoptotic function of Bim(EL), thereby promoting cell survival...
  88. ncbi BCL-XL dimerization by three-dimensional domain swapping
    Jason W O'Neill
    Divisions of Clinical Research and Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
    J Mol Biol 356:367-81. 2006
    ..Chemical crosslinking studies of Cys-substituted BCL-X(L) proteins demonstrate that 3DDS dimers form in synthetic lipid vesicles...
  89. ncbi Underexpression of transcriptional regulators is common in metastatic breast cancer cells overexpressing Bcl-xL
    Olga Mendez
    Centre d Oncologia Molecular, Institut de Recerca Oncologica, IDIBELL, Hospital Duran i Reynals, Gran Via s n, Km 2, 7, E 08907 L Hospitalet Ll, Barcelona, Spain
    Carcinogenesis 27:1169-79. 2006
    ....
  90. pmc Evidence that membrane insertion of the cytosolic domain of Bcl-xL is governed by an electrostatic mechanism
    Guruvasuthevan R Thuduppathy
    Department of Biology, Johns Hopkins University, 3400 N Charles St, Baltimore, MD 21218, USA
    J Mol Biol 359:1045-58. 2006
    ..Given the distinct biological activities of these conformations, the possibility that this conformational change might be a regulatory checkpoint for apoptosis is discussed...
  91. 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...
  92. ncbi Bcl-xL is overexpressed in hormone-resistant prostate cancer and promotes survival of LNCaP cells via interaction with proapoptotic Bak
    Carolina Castilla
    Department of Pathology, Hospitales Universitarios Virgen del Rocio, Avenida Manuel Siurot s n, Seville 41013, Spain
    Endocrinology 147:4960-7. 2006
    ..We propose that these interactions may provide mechanisms for suppressing the activity of proapoptotic Bax and Bak in prostate cancer cells and that Bcl-xL expression contributes to androgen resistance and progression of prostate cancer...
  93. ncbi Differential expression of STAT5 and Bcl-xL, and high expression of Neu and STAT3 in non-small-cell lung carcinoma
    S G Sánchez-Ceja
    Laboratorio de Patologia, Instituto Nacional de Enfermedades Respiratorias, Secretaria de Salud, Mexico, D F, Héroe de Nacozari No 137, Col Centro, C P 58000 Morelia, Michoacan, Mexico
    Lung Cancer 54:163-8. 2006
    ....
  94. ncbi PGAM5, a Bcl-XL-interacting protein, is a novel substrate for the redox-regulated Keap1-dependent ubiquitin ligase complex
    Shih Ching Lo
    Department of Biochemistry, University of Missouri, Columbia, Missouri 65211, USA
    J Biol Chem 281:37893-903. 2006
    ..The identification of PGAM5 as a novel substrate of Keap1 suggests that Keap1 regulates both transcriptional and post-transcriptional responses of mammalian cells to oxidative stress...
  95. 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)...
  96. ncbi Molecular basis of Bcl-xL's target recognition versatility revealed by the structure of Bcl-xL in complex with the BH3 domain of Beclin-1
    Wei Feng
    Department of Biochemistry, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, P R China
    J Mol Biol 372:223-35. 2007
    ..Systematic analysis of all known Bcl-xL/BH3 domain complexes helped us to identify the molecular basis underlying the capacity of Bcl-xL to recognize diverse target sequences...
  97. ncbi Clinicopathological correlations of Bcl-xL and Bax expression in differentiated thyroid carcinoma
    M Asunción Martínez-Brocca
    Endocrinology Unit, Hospital Universitario Virgen del Rocio, Seville, Spain
    Clin Endocrinol (Oxf) 68:190-7. 2008
    ....
  98. pmc Bcl-xL induces Drp1-dependent synapse formation in cultured hippocampal neurons
    Hongmei Li
    Department of Internal Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 105:2169-74. 2008
    ..These findings suggest that Bcl-xL positively regulates Drp1 to alter mitochondrial function in a manner that stimulates synapse formation...
  99. doi Bcl-XL and Bcl-2 expression in bilharzial squamous cell carcinoma of the urinary bladder: which protein is prognostic?
    Diaa A Hameed
    Department of Urology, Assiut University, Assiut, Egypt
    Urology 72:374-8. 2008
    ..This work studied the expression of Bcl-XL and Bcl-2 immunohistochemically in bilharzial-related squamous cell carcinoma of the urinary bladder and determined their prognostic value in relation to recurrence after radical cystectomy...
  100. pmc Identification of the major phosphorylation site in Bcl-xL induced by microtubule inhibitors and analysis of its functional significance
    Meenakshi Upreti
    Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
    J Biol Chem 283:35517-25. 2008
    ..These studies suggest that Bcl-xL phosphorylation induced by microtubule inhibitors plays a key pro-apoptotic role at least in part by disabling the ability of Bcl-xL to bind Bax...
  101. pmc ARF induces autophagy by virtue of interaction with Bcl-xl
    Julia Pimkina
    Division of Medical Sciences, the Smolensk State Medical Academy Graduate Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    J Biol Chem 284:2803-10. 2009
    ..The combined data support the premise that ARF induces autophagy in a p53-independent manner in part by virtue of its interaction with Bcl-xl...

Research Grants67

  1. NIH Director's Pioneer Award
    Junying Yuan; Fiscal Year: 2009
    ..No Abstract provided ..
  2. 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. ..
  3. 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) ..
  4. 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. ..
  5. Junichi Sadoshima; Fiscal Year: 2016
    ..The knowledge obtained from these experiments should be useful for developing specific strategies to limit myocardial injury in patients with ischemic heart disease. ..
  6. Apoptosis Control by Bcl-2 Family Members
    Craig B Thompson; Fiscal Year: 2012
    ....
  7. Vesna Jevtovic-Todorovic; Fiscal Year: 2014
    ..Using in-vivo and ex-vitro systems, this proposal aims to investigate the mechanisms involved in anesthesia-induced reactive oxygen-mediated neurodegeneration during developmental synaptogenesis. ..
  8. 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. ..
  9. 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. ..
  10. J Kevin Foskett; Fiscal Year: 2016
    ....
  11. Nicolas G Bazan; Fiscal Year: 2016
    ..We will thus contribute to apply this knowledge to the prevention, repair or amelioration of retinal degenerative diseases. ..
  12. Niketa A Patel; Fiscal Year: 2015
    ..By showing that alternative splicing of apoptotic genes modulate differentiation and maturation of pre-adipocytes, the proposed studies will establish a new paradigm for adipogenesis and reveal new targets for treatment of obesity. ..
  13. Ethanol and Bcl-2 Gene Interactions in the Developing CNS
    Marieta B Heaton; Fiscal Year: 2012
    ..In addition, purified P4 and P7 Bax will be subjected to CD analyses of protein conformation at the two ages, and ethanol effects on this conformation. ..
  14. PATHWAYS REGULATED BY CASPASE CLEAVED BCL XL
    Richard Vaillancourt; Fiscal Year: 2000
    ..We will determine whether the interaction between delta61 Bcl-XL and MEKK3 affects the ability of MEKK3 to activate any of these pathways. ..
  15. BcI-2 family in T lymphocyte homeostasis
    You Wen He; Fiscal Year: 2013
    ..The results from this study, if funded, will provide information important in designing vaccines to boost immune response to microbial pathogens. ..
  16. CYTOMEGALOVIRUS DNA REPLICATION AND INVERSION
    Edward S Mocarski; Fiscal Year: 2013
    ..This investigation will lead to a more complete understanding of the interplay of cellular and viral functions as determinants of cell fate. ..
  17. Zaneta Nikolovska-Coleska; Fiscal Year: 2014
    ....
  18. 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. ..
  19. CYNTHIA K MIRANTI; Fiscal Year: 2016
    ....
  20. 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. ..
  21. 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. ..
  22. The Molecular Basis of OX40 on CD4 T Cells
    Michael Croft; Fiscal Year: 2012
    ..abstract_text> ..
  23. Joseph T Opferman; Fiscal Year: 2014
    ..At the end of this study, we will have illuminated a previously unrecognized role for MCL-1 in promoting mitochondrial function. ..
  24. GENE THERAPY FOR LONG-TERM MYOCARDIAL PROTECTION
    Victor J Dzau; Fiscal Year: 2013
    ..Public Health Relevance: This proposal is to study the mechanisms responsible for 2-catenin and ROR3t-regulated T cell apoptosis. ..
  25. SMAC in chemoprevention of colon cancer
    Lin Zhang; Fiscal Year: 2011
    ..The proposed studies will provide new insights into the anti-neoplastic effects of NSAIDs. In the long run, the results of these studies could be useful for developing improved strategies and agents for chemoprevention of colon cancer. ..
  26. Regulation of apoptosis by Bcl-XL, Bak and Bax
    Chi Li; Fiscal Year: 2009
    ..Oligonucleotide-based microarray analysis will be performed to examine the changes in gene expression patterns in response to Bak or Bax expression. Genes whose expression may be involved in apoptosis regulation will be further studied. ..
  27. "Conserved Cell Death Pathways in Mammals and Yeast"
    J Marie Hardwick; Fiscal Year: 2010
    ..We expect that these newly unidentified yeast factors will be involved in the maintenance, biogenesis and degradation of mitochondria, and in close proximity to the regulation of bioenergetics. ..
  28. Regulation of Apoptotic Signaling Pathways by Alpha-Crystallins in the Ocular Len
    David W Li; Fiscal Year: 2010
    ..abstract_text> ..
  29. THE ROLE OF MITOCHONDRIAL CHANNELS IN CELL DEATH
    Kathleen W Kinnally; Fiscal Year: 2010
    ..These experiments may identify novel therapeutic targets, e.g., MAC, to modulate apoptosis in cancer and other pathologies, e.g., myocardial infarction. ..
  30. IN VITRO STIMULATION OF HIV SPECIFIC CD8+ T CELLS
    Peter D Katsikis; Fiscal Year: 2010
    ..These studies may lead to new treatments for HIV infection a serious public health problem. ..
  31. Maurizio Pellecchia; Fiscal Year: 2016
    ....
  32. Elizabeth Ann Jonas; Fiscal Year: 2014
    ..In the absence of Bcl-xL the pore will not open properly, and defects in calcium efflux from mitochondria will occur. These defects may contribute to a loss of synaptic plasticity. ..
  33. Stat3 in Epitherlial Carcinogenesis
    John DiGiovanni; Fiscal Year: 2012
    ..Furthermore, the proposed studies will provide additional evidence that keratinocyte stem cells, particularly those found in the bulge region of hair follicles, may be the primary target cells for tumor development in mouse skin. ..
  34. The Role of Zinc Finger Genes in Leukemogenesis
    Sinisa Dovat; Fiscal Year: 2013
    ..Our research will provide new and important information on the mechanisms controlling the proliferation of hematopoietic cells and will yield insights into the pathophysiology and treatment of leukemia. ..
  35. Role and Activation Status of IRS1/2 in IL-4-induced Protection from Cell Death.
    HOLLY A PORTER; Fiscal Year: 2010
    ..Understanding the molecular programming of a cell may also allow for the better prediction of a patient's response to treatment. ..
  36. Nit1-mediated signaling in T cells
    Jianke Zhang; Fiscal Year: 2010
    ..The results will facilitate the development of effective preventive and therapeutic approaches. ..
  37. 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. ..
  38. Rb, p53, & Bcl-2 Proteins in Apoptosis
    STEVEN WEINTRAUB; Fiscal Year: 2007
    ..These studies may lead to the identification of cellular targets that allow for the development of more efficacious and less toxic antineoplastic therapies. [unreadable] [unreadable]..
  39. John Karanicolas; Fiscal Year: 2016
    ..By combining this approach with in vitro biochemical screening, we expect to identify novel inhibitors of protei interactions involving each of three well-validated cancer targets: Bcl-xL, survivin, and b- TrCP. ..
  40. TAXANE INDUCED APOPTOSIS--REGULATION IN BREAST CA CELLS
    Kapil Bhalla; Fiscal Year: 2002
    ..These in vitro studies may define the potential molecular targets or elucidate mechanisms that could be manipulated to promote taxane-induced apoptosis of breast cancer cells. ..
  41. MARK REID PHILIPS; Fiscal Year: 2015
    ..We propose to study the cell biology and physiology of K-Ras phosphorylation to better understand how to exploit this process to develop anti-cancer drugs. ..
  42. ACTIVATION OF XENOGENEIC ENDOTHELIUM TO RESIST INJURY
    Agustin P Dalmasso; Fiscal Year: 2010
    ..This will also provide knowledge for new treatments for vascular diseases, including ischemia and atherosclerosis. ..
  43. Toll-like receptor signaling in the generation of B1b cell memory
    Kishore R Alugupalli; Fiscal Year: 2012
    ..Identifying the role of TLR and BLyS signaling in B1b cell expansion and long-term maintenance will provide novel approaches for the generation of effective vaccines. ..
  44. The MRAD9 Radioresistance Gene
    Howard B Lieberman; Fiscal Year: 2013
    ..abstract_text> ..
  45. Anuja Ghorpade; Fiscal Year: 2016
    ..Our studies will provide a better understanding of the specific mechanistic contributions of activated astrocytes to HIV-1-neuropathogensis and neuroinflammation. ..
  46. Role of Astrocyte Injury in Neuroprotection
    Martin A Philbert; Fiscal Year: 2012
    ..We propose here that in the acute phases of CNS injury, loss of neuronal function (silencing) is elicited by adenosine and may spare the neuron from the deleterious effects of oxidative stress and excitotoxicity. ..
  47. JONATHAN DAVID KATZ; Fiscal Year: 2014
    ..abstract_text> ..
  48. Proteasome/HDAC Inhibition in Leukemia/MDS; Phase I Trial and Correlative Studies
    Steven Grant; Fiscal Year: 2010
    ....
  49. Tri-modal Polymeric Micelles for 'See &Treat'Applications in Surgical Oncology
    Glen S Kwon; Fiscal Year: 2012
    ..Advances in integrated optical imaging and therapeutic capability of biocompatible PEG-b-PCL micelles will enable tenable nano-technology applications in surgical oncology and rapid translation into clinical trials. ..
  50. Phase I Trial of Bortezomib and Romidepsin in CLL and Small Cell Lymphoma
    Steven Grant; Fiscal Year: 2010
    ..This will position us to perform future trials that will determine the effectiveness of this novel drug combination in patients with CLL or SLL and address the validity of our preclinical pharmacodynamic observations. ..
  51. Biomarkers of response to Hsp90 inhibitors in triple-negative breast cancer
    Gabriela Chiosis; Fiscal Year: 2013
    ....
  52. Tumor-targeted silencing of Bcl-2/Bcl-xL by the self-assembled siRNA-nanovectors
    Liang Xu; Fiscal Year: 2010
    ..Successfully carried out, our studies will provide proof-of-concept that siRNA can be delivered by the self-assembled nanovectors for tumor-targeted silencing of the genes critical for cancer progression and resistance. ..
  53. LPD Nanoparticles in Anti-Cancer Therapy
    Leaf Huang; Fiscal Year: 2012
    ..A self-assembled nanoparticle formulation will be used as a delivery vehicle. The project uses lung cancer and lung metastasis in mice as the disease model. ..
  54. 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. ..
  55. Role of RNA Binding Proteins in BCR/ABL Leukemogenesis
    Danilo Perrotti; Fiscal Year: 2012
    ..Thus, it is clear that, if successful, the proposed research will have a strong impact on leukemia research and patient care. ..
  56. Role of BCL-xL in synaptic plasticity in the hippocampus
    Elizabeth Ann Jonas; Fiscal Year: 2012
    ..Our studies will shed light on basic properties that strengthen the synapse during learning and memory or weaken it during synaptic dysfunction or neurodegeneration. ..
  57. Mechanisms of In Vivo Ethanol-Induced Mitochondrial Depolarization
    Zhi Zhong; Fiscal Year: 2010
    ....
  58. Suppression of vascular endothelial cell inflammation
    Xiao Feng Yang; Fiscal Year: 2013
    ..abstract_text> ..
  59. Transcriptional regulation of apoptosis
    James J Manfredi; Fiscal Year: 2013
    ....
  60. Timothy C Chambers; Fiscal Year: 2014
    ..At the completion of these experiments, we hope to have gained considerable new insight into the molecular mechanisms of action of this important class of cancer drugs. ..
  61. Analysis of Radiomitigative Cell Signaling
    Gabor J Tigyi; Fiscal Year: 2012
    ..The objective of this grant application is to elucidate the an- tiapoptotic mechanism of action unique to the LPA2 receptor subtype ..
  62. Cellular plasticity and survival mechanisms in medulloblastoma stem cells
    Ronnie Yoo; Fiscal Year: 2013
    ..STAT3 and its downstream target Klf4, are collaboratively regulating the expression of survival genes Mcl-1 and Bclx. In the second aim, the cooperation of STAT3 and Klf4 in survival gene regulation will be tested by double KD of ..
  63. Targeting BCL-XL Expression in Mesothelioma
    W Smythe; Fiscal Year: 2006
    ..Upstream targets regulating bcl-xl expression for use in future therapeutic paradigms may be identified. ..
  64. Role of NIX in Erythroid Maturation
    PAUL NEY; Fiscal Year: 2007
    ..We propose to explore that possibility in experiments with Nix mice and other BCL2-related mouse strains. [unreadable] [unreadable] [unreadable]..
  65. The Role of Bcl-x in Murine Spermatogenesis
    Edmund Rucker; Fiscal Year: 2004
    ..Resultant mutants will demonstrate whether Bcl-x and Bax compete in determining the apoptotic fate of spermatocytes during murine spermatogenesis. ..
  66. MOLECULAR BASIS OF RETINAL APOPTOSIS AND RETINOBLASTOMA
    JOLENE WINDLE; Fiscal Year: 1999
    ....
  67. OSTEOCLASTS FROM TRANSGENIC MICE
    G Roodman; Fiscal Year: 2009
    ..Our long-term goal will be to characterize the role of ADAM8/a9b1 in the bone destruction which accompanies collagen induced arthritis, which will be started in grant year 5. ..