Summary: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.

Top Publications

  1. ncbi Multilineage potential of adult human mesenchymal stem cells
    M F Pittenger
    Osiris Therapeutics, 2001 Aliceanna Street, Baltimore, MD 21231 3043, USA
    Science 284:143-7. 1999
  2. ncbi The BCL-2 protein family: opposing activities that mediate cell death
    Richard J Youle
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, The National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Rev Mol Cell Biol 9:47-59. 2008
  3. ncbi The hallmarks of cancer
    D Hanahan
    Department of Biochemistry, Hormone Research Institute, University of California at San Francisco, 94143, USA
    Cell 100:57-70. 2000
  4. ncbi Free radicals and antioxidants in normal physiological functions and human disease
    Marian Valko
    Faculty of Chemical and Food Technology, Slovak Technical University, SK 812 37 Bratislava, Slovakia
    Int J Biochem Cell Biol 39:44-84. 2007
  5. ncbi Cancer genes and the pathways they control
    Bert Vogelstein
    Howard Hughes Medical Institute and The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University Medical Institutions, Baltimore, Maryland 21231, USA
    Nat Med 10:789-99. 2004
  6. pmc Apoptosis: a review of programmed cell death
    Susan Elmore
    NIEHS, Laboratory of Experimental Pathology, Research Triangle Park, North Carolina 27709, USA
    Toxicol Pathol 35:495-516. 2007
  7. ncbi Cell death: critical control points
    Nika N Danial
    Howard Hughes Medical Institute, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cell 116:205-19. 2004
  8. ncbi Self-eating and self-killing: crosstalk between autophagy and apoptosis
    M Chiara Maiuri
    INSERM, U848, F 94805 Villejuif, France
    Nat Rev Mol Cell Biol 8:741-52. 2007
  9. ncbi Notch signaling: cell fate control and signal integration in development
    S Artavanis-Tsakonas
    Massachusetts General Hospital Cancer Center, Department of Cell Biology, Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA
    Science 284:770-6. 1999
  10. 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

Detail Information

Publications532 found, 100 shown here

  1. ncbi Multilineage potential of adult human mesenchymal stem cells
    M F Pittenger
    Osiris Therapeutics, 2001 Aliceanna Street, Baltimore, MD 21231 3043, USA
    Science 284:143-7. 1999
    ..These adult stem cells could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages. Individual stem cells were identified that, when expanded to colonies, retained their multilineage potential...
  2. ncbi The BCL-2 protein family: opposing activities that mediate cell death
    Richard J Youle
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, The National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Rev Mol Cell Biol 9:47-59. 2008
    ..activities, have been studied intensively for the past decade owing to their importance in the regulation of apoptosis, tumorigenesis and cellular responses to anti-cancer therapy...
  3. ncbi The hallmarks of cancer
    D Hanahan
    Department of Biochemistry, Hormone Research Institute, University of California at San Francisco, 94143, USA
    Cell 100:57-70. 2000
  4. ncbi Free radicals and antioxidants in normal physiological functions and human disease
    Marian Valko
    Faculty of Chemical and Food Technology, Slovak Technical University, SK 812 37 Bratislava, Slovakia
    Int J Biochem Cell Biol 39:44-84. 2007
    ..and maintain the oncogenic phenotype of cancer cells, however, ROS can also induce cellular senescence and apoptosis and can therefore function as anti-tumourigenic species...
  5. ncbi Cancer genes and the pathways they control
    Bert Vogelstein
    Howard Hughes Medical Institute and The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University Medical Institutions, Baltimore, Maryland 21231, USA
    Nat Med 10:789-99. 2004
    ..The purposes of this review are to highlight examples of progress in these areas, indicate where knowledge is scarce and point out fertile grounds for future investigation...
  6. pmc Apoptosis: a review of programmed cell death
    Susan Elmore
    NIEHS, Laboratory of Experimental Pathology, Research Triangle Park, North Carolina 27709, USA
    Toxicol Pathol 35:495-516. 2007
    The process of programmed cell death, or apoptosis, is generally characterized by distinct morphological characteristics and energy-dependent biochemical mechanisms...
  7. ncbi Cell death: critical control points
    Nika N Danial
    Howard Hughes Medical Institute, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cell 116:205-19. 2004
    ..b>Apoptosis has proven to be tightly interwoven with other essential cell pathways...
  8. ncbi Self-eating and self-killing: crosstalk between autophagy and apoptosis
    M Chiara Maiuri
    INSERM, U848, F 94805 Villejuif, France
    Nat Rev Mol Cell Biol 8:741-52. 2007
    The functional relationship between apoptosis ('self-killing') and autophagy ('self-eating') is complex in the sense that, under certain circumstances, autophagy constitutes a stress adaptation that avoids cell death (and suppresses ..
  9. ncbi Notch signaling: cell fate control and signal integration in development
    S Artavanis-Tsakonas
    Massachusetts General Hospital Cancer Center, Department of Cell Biology, Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA
    Science 284:770-6. 1999
    ..Notch activity affects the implementation of differentiation, proliferation, and apoptotic programs, providing a general developmental tool to influence organ formation and morphogenesis...
  10. 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...
  11. ncbi Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes
    Alexandra E Butler
    Division of Endocrinology and Diabetes, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
    Diabetes 52:102-10. 2003
    ..We measured relative beta-cell volume, frequency of beta-cell apoptosis and replication, and new islet formation from exocrine ducts (neogenesis)...
  12. pmc Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death
    M C Wei
    Howard Hughes Medical Institute, Departments of Pathology and Medicine, Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Science 292:727-30. 2001
    Multiple death signals influence mitochondria during apoptosis, yet the critical initiating event for mitochondrial dysfunction in vivo has been unclear...
  13. ncbi MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells
    Jennifer A Chan
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Res 65:6029-33. 2005
    ..Our data suggest that aberrantly expressed miR-21 may contribute to the malignant phenotype by blocking expression of critical apoptosis-related genes.
  14. pmc Autophagy in health and disease: a double-edged sword
    Takahiro Shintani
    University of Michigan, Life Sciences Institute, Ann Arbor, MI 48109 2216, USA
    Science 306:990-5. 2004
    ..By mostly morphological studies, autophagy has been linked to disease processes. Whether autophagy protects from or causes disease is unclear. Here, we summarize current knowledge about the role of autophagy in disease and health...
  15. ncbi Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases
    Michael T Lin
    Department of Neurology and Neuroscience, Weill Medical College of Cornell University, Room F 610, 525 East 68th Street, New York 10021, USA
    Nature 443:787-95. 2006
    ..Thus, therapies targeting basic mitochondrial processes, such as energy metabolism or free-radical generation, or specific interactions of disease-related proteins with mitochondria, hold great promise...
  16. ncbi Requirement for p53 and p21 to sustain G2 arrest after DNA damage
    F Bunz
    The Howard Hughes Medical Institute and The Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA
    Science 282:1497-501. 1998
    ..Thus, p53 and p21 appear to be essential for maintaining the G2 checkpoint in human cells...
  17. ncbi Roles of CHOP/GADD153 in endoplasmic reticulum stress
    S Oyadomari
    Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860 8556, Japan
    Cell Death Differ 11:381-9. 2004
    ..One of the components of the ER stress-mediated apoptosis pathway is C/EBP homologous protein (CHOP), also known as growth arrest- and DNA damage-inducible gene 153 (..
  18. ncbi bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila
    Julius Brennecke
    European Molecular Biology Laboratory, Meyerhofstr 1, 69117 Heidelberg, Germany
    Cell 113:25-36. 2003
    ..Although many proteins that control cell proliferation and apoptosis have been identified, the means by which these effectors are linked to the patterning machinery remain poorly ..
  19. doi The miR-34 family in cancer and apoptosis
    H Hermeking
    Experimental and Molecular Pathology, Institute of Pathology, Ludwig Maximilians University Munich, Thalkirchner Str 36, D 80337 Munich, Germany
    Cell Death Differ 17:193-9. 2010
    ..Ectopic miR-34 expression induces apoptosis, cell-cycle arrest or senescence...
  20. ncbi Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis
    H Li
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 94:491-501. 1998
    ..Coexpression of BclxL inhibits all the apoptotic changes induced by tBID. Our results indicate that BID is a mediator of mitochondrial damage induced by Casp8...
  21. ncbi TIGAR, a p53-inducible regulator of glycolysis and apoptosis
    Karim Bensaad
    The Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, UK
    Cell 126:107-20. 2006
    ..protein prevents cancer development through various mechanisms, including the induction of cell-cycle arrest, apoptosis, and the maintenance of genome stability...
  22. ncbi hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase
    H Vaziri
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Cell 107:149-59. 2001
    DNA damage-induced acetylation of p53 protein leads to its activation and either growth arrest or apoptosis. We show here that the protein product of the gene hSIR2(SIRT1), the human homolog of the S...
  23. pmc Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas
    Wen Xue
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Nature 445:656-60. 2007
    ..damage or deregulation of mitogenic oncogenes, by leading to the induction of various cell cycle checkpoints, apoptosis or cellular senescence...
  24. ncbi p53 in health and disease
    Karen H Vousden
    Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK
    Nat Rev Mol Cell Biol 8:275-83. 2007
    ..Although the function of p53 as a tumour suppressor ensures that we can't live without it, an integrated view of p53 suggests that not all of its functions are conducive to a long and healthy life...
  25. pmc The Beclin 1 network regulates autophagy and apoptosis
    R Kang
    Department of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA
    Cell Death Differ 18:571-80. 2011
    ..Interestingly, caspase-mediated cleavage of Beclin 1 promotes crosstalk between apoptosis and autophagy...
  26. ncbi TSC2 mediates cellular energy response to control cell growth and survival
    Ken Inoki
    Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
    Cell 115:577-90. 2003
    ..Furthermore, TSC2 and its phosphorylation by AMPK protect cells from energy deprivation-induced apoptosis. These observations demonstrate a model where TSC2 functions as a key player in regulation of the common mTOR ..
  27. ncbi The mammalian unfolded protein response
    Martin Schroder
    School of Biological and Biomedical Sciences, University of Durham, Durham DH1 3LE, United Kingdom
    Annu Rev Biochem 74:739-89. 2005
    ..Finally, we summarize data that demonstrate that UPR signaling feeds into decision making in other processes previously thought to be unrelated to ER function, e.g., eukaryotic starvation responses and differentiation programs...
  28. ncbi Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases
    Gary L Johnson
    Department of Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    Science 298:1911-2. 2002
    ..The p38 MAPKs are activated by inflammatory cytokines and environmental stresses and may contribute to diseases like asthma and autoimmunity...
  29. ncbi Biologic basis for interleukin-1 in disease
    C A Dinarello
    Department of Medicine, Tufts University, Boston, MA USA
    Blood 87:2095-147. 1996
    ..At the end of each section, a short commentary summarizes what the author considers established or controversial topics linking the biology of IL-1 to mechanisms of disease...
  30. pmc Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor
    Zhenyu Yue
    Laboratory of Molecular Biology, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 100:15077-82. 2003
    ..properties of beclin 1 suggest a role in two fundamentally important cell biological pathways: autophagy and apoptosis. We show here that beclin 1-/- mutant mice die early in embryogenesis and beclin 1+/- mutant mice suffer from a ..
  31. ncbi Anticancer activities of histone deacetylase inhibitors
    Jessica E Bolden
    Cancer Immunology Program, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne 3002, Victoria, Australia
    Nat Rev Drug Discov 5:769-84. 2006
  32. pmc The BCL-2 family reunion
    Jerry E Chipuk
    Department of Immunology, St Jude Children s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA
    Mol Cell 37:299-310. 2010
    ..originally characterized with respect to their roles in controlling outer mitochondrial membrane integrity and apoptosis. Current observations expand BCL-2 family function to include numerous cellular pathways...
  33. pmc Autophagy and the integrated stress response
    Guido Kroemer
    INSERM, U848, 39 rue Calmette Desmoulins, 94805 Villejuif, France
    Mol Cell 40:280-93. 2010
    ..Thus, autophagy is a cell biological process that is a central component of the integrated stress response...
  34. ncbi Live or let die: the cell's response to p53
    Karen H Vousden
    Regulation of Cell Growth Laboratory, National Cancer Institute at Frederick, 1050 Boyles Street, Frederick, Maryland 21702, USA
    Nat Rev Cancer 2:594-604. 2002
  35. ncbi The pathophysiology of mitochondrial cell death
    Douglas R Green
    Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA
    Science 305:626-9. 2004
    In the mitochondrial pathway of apoptosis, caspase activation is closely linked to mitochondrial outer membrane permeabilization (MOMP)...
  36. ncbi Cellular survival: a play in three Akts
    S R Datta
    Division of Neuroscience, Children s Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115 USA
    Genes Dev 13:2905-27. 1999
  37. pmc Identification of RIP1 kinase as a specific cellular target of necrostatins
    Alexei Degterev
    Tufts University, School of Medicine, Department of Biochemistry, 136 Harrison Avenue, Boston, Massachusetts 02111, USA
    Nat Chem Biol 4:313-21. 2008
    ..Overall, our data establish necrostatins as the first-in-class inhibitors of RIP1 kinase, the key upstream kinase involved in the activation of necroptosis...
  38. ncbi In vivo activation of the p53 pathway by small-molecule antagonists of MDM2
    Lyubomir T Vassilev
    Department of Discovery Oncology, Roche Research Center, Hoffmann La Roche, Inc, Nutley, NJ 07110, USA
    Science 303:844-8. 2004
    ..These compounds bind MDM2 in the p53-binding pocket and activate the p53 pathway in cancer cells, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts in nude mice.
  39. 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
    Tissue homeostasis is regulated by apoptosis, the cell-suicide programme that is executed by proteases called caspases...
  40. pmc The Bcl-2 apoptotic switch in cancer development and therapy
    J M Adams
    Department of Molecular Genetics of Cancer, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
    Oncogene 26:1324-37. 2007
    Impaired apoptosis is both critical in cancer development and a major barrier to effective treatment...
  41. ncbi Glioma stem cells promote radioresistance by preferential activation of the DNA damage response
    Shideng Bao
    Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nature 444:756-60. 2006
    ..Targeting DNA damage checkpoint response in cancer stem cells may overcome this radioresistance and provide a therapeutic model for malignant brain cancers...
  42. pmc Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF
    V A Fadok
    Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA
    J Clin Invest 101:890-8. 1998
    b>Apoptosis in vivo is followed almost inevitably by rapid uptake into adjacent phagocytic cells, a critical process in tissue remodeling, regulation of the immune response, or resolution of inflammation...
  43. doi The unfolded protein response: controlling cell fate decisions under ER stress and beyond
    Claudio Hetz
    Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, P O BOX 70086, Chile
    Nat Rev Mol Cell Biol 13:89-102. 2012
    ..signalling network that orchestrates the recovery of ER function, and failure to adapt to ER stress results in apoptosis. Progress in the field has provided insight into the regulatory mechanisms and signalling crosstalk of the three ..
  44. ncbi Hereditary early-onset Parkinson's disease caused by mutations in PINK1
    Enza Maria Valente
    CSS IRCCS, Mendel Institute, Viale Regina Margherita 261, 00198 Rome, Italy
    Science 304:1158-60. 2004
    ..These data provide a direct molecular link between mitochondria and the pathogenesis of PD...
  45. ncbi Release of chromatin protein HMGB1 by necrotic cells triggers inflammation
    Paola Scaffidi
    DIBIT, Istituto Scientifico San Raffaele, 20132 Milano, Italy
    Nature 418:191-5. 2002
    ..Thus, cells undergoing apoptosis are programmed to withhold the signal that is broadcast by cells that have been damaged or killed by trauma.
  46. pmc The landscape of somatic copy-number alteration across human cancers
    Rameen Beroukhim
    Cancer Program and Medical and Population Genetics Group, The Broad Institute of M I T and Harvard, 7 Cambridge Center
    Nature 463:899-905. 2010
    ..Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-kappaBeta pathway...
  47. ncbi A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma
    G Ambrosini
    Boyer Center for Molecular Medicine, Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06536, USA
    Nat Med 3:917-21. 1997
    Inhibitors of programmed cell death (apoptosis) aberrantly prolonging cell viability may contribute to cancer by facilitating the insurgence of mutations and by promoting resistance to therapy...
  48. doi MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN
    Hua Yang
    Department of Interdisciplinary Oncology, H Lee Moffitt Cancer Center and Research Institute, University of South Florida College of Medicine, Tampa, Florida 33612, USA
    Cancer Res 68:425-33. 2008
    ..These findings indicate that deregulation of miRNAs is a recurrent event in human ovarian cancer and that miR-214 induces cell survival and cisplatin resistance primarily through targeting the PTEN/Akt pathway...
  49. pmc Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma
    Erwin G Van Meir
    Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA
    CA Cancer J Clin 60:166-93. 2010
  50. ncbi Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase
    Anne Brunet
    Division of Neuroscience, Children s Hospital, and Department of Neurobiology, Center for Blood Research CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA
    Science 303:2011-5. 2004
    ..Thus, one way in which members of the Sir2 family of proteins may increase organismal longevity is by tipping FOXO-dependent responses away from apoptosis and toward stress resistance.
  51. doi Blinded by the Light: The Growing Complexity of p53
    Karen H Vousden
    The Beatson Institute for Cancer Research, Garscube Estate, Glasgow, UK
    Cell 137:413-31. 2009
    ..Control of p53's transcriptional activity is crucial for determining which p53 response is activated, a decision we must understand if we are to exploit efficiently the next generation of drugs that selectively activate or inhibit p53...
  52. pmc Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress
    Ira Tabas
    Department of Medicine, Anatomy and Cell Biology, Columbia University, New York, NY 10032, USA
    Nat Cell Biol 13:184-90. 2011
    ..reticulum (ER) function is a fundamentally important property of all cells, but ER stress can also lead to apoptosis. In settings of chronic ER stress, the associated apoptosis may contribute to pathophysiological processes ..
  53. ncbi Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy
    Sophie Pattingre
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    Cell 122:927-39. 2005
    b>Apoptosis and autophagy are both tightly regulated biological processes that play a central role in tissue homeostasis, development, and disease...
  54. ncbi Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha
    D R Alessi
    Medical Research Council Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dundee, DD1 4HN, Scotland
    Curr Biol 7:261-9. 1997
    ..The phosphorylation of both residues is required for maximal activation of PKB. The kinases that phosphorylate PKB are, however, unknown...
  55. ncbi Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells
    Lisa B Frankel
    Biotech Research and Innovation Centre, Bioinformatics Centre, University of Copenhagen, DK 2200 N Copenhagen, Denmark
    J Biol Chem 283:1026-33. 2008
    ..microRNA is overexpressed in a wide variety of cancers and has been causally linked to cellular proliferation, apoptosis, and migration. Inhibition of mir-21 in MCF-7 breast cancer cells causes reduced cell growth...
  56. ncbi Negative control of p53 by Sir2alpha promotes cell survival under stress
    J Luo
    Institute of Cancer Genetics and Department of Pathology, College of Physicians and Surgeons, Columbia University, 1150 St Nicholas Avenue, New York, NY 10032, USA
    Cell 107:137-48. 2001
    ..Furthermore, Sir2alpha represses p53-dependent apoptosis in response to DNA damage and oxidative stress, whereas expression of a Sir2alpha point mutant increases the ..
  57. ncbi miR-21-mediated tumor growth
    M L Si
    Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62794, USA
    Oncogene 26:2799-803. 2007
    ..Furthermore, this anti-miR-21-mediated cell growth inhibition was associated with increased apoptosis and decreased cell proliferation, which could be in part owing to downregulation of the antiapoptotic Bcl-2 in ..
  58. pmc Deciphering the rules of programmed cell death to improve therapy of cancer and other diseases
    Andreas Strasser
    The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    EMBO J 30:3667-83. 2011
    b>Apoptosis, the major form of programmed cell death in metazoan organisms, plays critical roles in normal development, tissue homeostasis and immunity, and its disturbed regulation contributes to many pathological states, including cancer,..
  59. ncbi Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor
    A Brunet
    Children s Hospital and Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 96:857-68. 1999
    Survival factors can suppress apoptosis in a transcription-independent manner by activating the serine/ threonine kinase Akt, which then phosphorylates and inactivates components of the apoptotic machinery, including BAD and Caspase 9...
  60. ncbi Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways
    H Ichijo
    Department of Biochemistry, The Cancer Institute, Tokyo, Japanese Foundation for Cancer Research, 1 37 1 Kami Ikebukuro, Toshima ku, Tokyo 170, Japan
    Science 275:90-4. 1997
    ..Moreover, TNF-alpha-induced apoptosis was inhibited by a catalytically inactive form of ASK1...
  61. pmc CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum
    H Zinszner
    Skirball Institute of Biomolecular Medicine, the Departments of Medicine, Cell Biology, and the Kaplan Cancer Center, New York University NYU Medical Center, New York, New York 10016 USA
    Genes Dev 12:982-95. 1998
    ..CHOP therefore has a role in the induction of cell death under conditions associated with malfunction of the ER and may also have a role in cellular regeneration under such circumstances...
  62. pmc Inhibition of macroautophagy triggers apoptosis
    Patricia Boya
    CNRS UMR 8125, Institut Gustave Roussy, Pavillon de Recherche 1, 39 rue Camille Desmoulins, F 94805 Villejuif, France
    Mol Cell Biol 25:1025-40. 2005
    ..Cell death occurred through apoptosis (type 1 cell death), since it was reduced by stabilization of mitochondrial membranes (with Bcl-2 or vMIA, a ..
  63. pmc Tumor suppression in the absence of p53-mediated cell-cycle arrest, apoptosis, and senescence
    Tongyuan Li
    Institute for Cancer Genetics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Cell 149:1269-83. 2012
    Cell-cycle arrest, apoptosis, and senescence are widely accepted as the major mechanisms by which p53 inhibits tumor formation. Nevertheless, it remains unclear whether they are the rate-limiting steps in tumor suppression...
  64. ncbi Transcriptional activation of miR-34a contributes to p53-mediated apoptosis
    Nina Raver-Shapira
    Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel
    Mol Cell 26:731-43. 2007
    ..Notably, inactivation of miR-34a strongly attenuates p53-mediated apoptosis in cells exposed to genotoxic stress, whereas overexpression of miR-34a mildly increases apoptosis...
  65. pmc Identification of selective inhibitors of cancer stem cells by high-throughput screening
    Piyush B Gupta
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 138:645-59. 2009
    ..This study demonstrates the ability to identify agents with specific toxicity for epithelial CSCs...
  66. doi Crosstalk between apoptosis, necrosis and autophagy
    Vassiliki Nikoletopoulou
    Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, Heraklion 71110, Crete, Greece
    Biochim Biophys Acta 1833:3448-59. 2013
    b>Apoptosis and necrosis are the two major modes of cell death, the molecular mechanisms of which have been extensively studied...
  67. doi Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy
    Peter E Czabotar
    1 The Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, 1G Royal Parade, Parkville, Victoria 3052, Australia 2
    Nat Rev Mol Cell Biol 15:49-63. 2014
    The BCL-2 protein family determines the commitment of cells to apoptosis, an ancient cell suicide programme that is essential for development, tissue homeostasis and immunity...
  68. ncbi Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade
    P Li
    Howard Hughes Medical Institute, and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 75235, USA
    Cell 91:479-89. 1997
  69. pmc Significance analysis of microarrays applied to the ionizing radiation response
    V G Tusher
    Departments of Medicine and Biochemistry, Stanford University, 269 Campus Drive, Center for Clinical Sciences Research 1115, Stanford, CA 94305-5151, USA
    Proc Natl Acad Sci U S A 98:5116-21. 2001
    ..Of the 34 genes, 19 were involved in cell cycle regulation and 3 in apoptosis. Surprisingly, four nucleotide excision repair genes were induced, suggesting that this repair pathway for UV-..
  70. doi Molecular mechanisms of necroptosis: an ordered cellular explosion
    Peter Vandenabeele
    Department for Molecular Biomedical Research, VIB, Ghent University, Belgium
    Nat Rev Mol Cell Biol 11:700-14. 2010
    For a long time, apoptosis was considered the sole form of programmed cell death during development, homeostasis and disease, whereas necrosis was regarded as an unregulated and uncontrollable process...
  71. ncbi An inhibitor of Bcl-2 family proteins induces regression of solid tumours
    Tilman Oltersdorf
    Idun Pharmaceuticals, 9380 Judicial Drive, San Diego, California 92121, USA
    Nature 435:677-81. 2005
    Proteins in the Bcl-2 family are central regulators of programmed cell death, and members that inhibit apoptosis, such as Bcl-X(L) and Bcl-2, are overexpressed in many cancers and contribute to tumour initiation, progression and ..
  72. doi RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis
    Duan Wu Zhang
    Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China
    Science 325:332-6. 2009
    ..tumor necrosis factor (TNF) or other agonists; however, the underlying mechanism differentiating necrosis from apoptosis is largely unknown...
  73. 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...
  74. pmc AMPK phosphorylation of raptor mediates a metabolic checkpoint
    Dana M Gwinn
    Molecular and Cell Biology Laboratory, Dulbecco Center for Cancer Research, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
    Mol Cell 30:214-26. 2008
    ..These findings uncover a conserved effector of AMPK that mediates its role as a metabolic checkpoint coordinating cell growth with energy status...
  75. pmc Programmed cell death in animal development and disease
    Yaron Fuchs
    Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
    Cell 147:742-58. 2011
    ..We also discuss the function and regulation of apoptotic proteins, including caspases, the key executioners of apoptosis, and review the nonlethal functions of these proteins in diverse developmental processes, such as cell ..
  76. ncbi Signal transduction by the JNK group of MAP kinases
    R J Davis
    Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester 01605, USA
    Cell 103:239-52. 2000
  77. ncbi Cisplatin: mode of cytotoxic action and molecular basis of resistance
    Zahid H Siddik
    Department of Experimental Therapeutics, Unit 104, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030 4009, USA
    Oncogene 22:7265-79. 2003
    ..transduction pathways, including those involving ATR, p53, p73, and MAPK, and culminate in the activation of apoptosis. DNA damage-mediated apoptotic signals, however, can be attenuated, and the resistance that ensues is a major ..
  78. pmc Reactive oxygen species, cellular redox systems, and apoptosis
    Magdalena L Circu
    Department of Molecular and Cellular Physiology, Louisiana University Health Sciences Center, Shreveport, LA 71130, USA
    Free Radic Biol Med 48:749-62. 2010
    ..Cell apoptosis is initiated by extracellular and intracellular signals via two main pathways, the death receptor- and the ..
  79. ncbi Molecular characterization of mitochondrial apoptosis-inducing factor
    S A Susin
    Centre National de la Recherche Scientifique, UPR 420, Villejuif, France
    Nature 397:441-6. 1999
    Mitochondria play a key part in the regulation of apoptosis (cell death). Their intermembrane space contains several proteins that are liberated through the outer membrane in order to participate in the degradation phase of apoptosis...
  80. ncbi Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin
    Ira E Clark
    Nature 441:1162-6. 2006
    ..The role of the pink1-parkin pathway in regulating mitochondrial function underscores the importance of mitochondrial dysfunction as a central mechanism of Parkinson's disease pathogenesis...
  81. ncbi Apoptosis: controlled demolition at the cellular level
    Rebecca C Taylor
    Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland
    Nat Rev Mol Cell Biol 9:231-41. 2008
    b>Apoptosis is characterized by a series of dramatic perturbations to the cellular architecture that contribute not only to cell death, but also prepare cells for removal by phagocytes and prevent unwanted immune responses...
  82. ncbi Restoration of p53 function leads to tumour regression in vivo
    Andrea Ventura
    Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    Nature 445:661-5. 2007
    ..for tumour regression is dependent on the tumour type, with the main consequence of p53 restoration being apoptosis in lymphomas and suppression of cell growth with features of cellular senescence in sarcomas...
  83. ncbi Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation
    K P Hoeflich
    Ontario Cancer Institute Princess Margaret Hospital, Toronto, Canada
    Nature 406:86-90. 2000
    ..Thus, GSK-3beta facilitates NF-kappaB function...
  84. ncbi NF-kappaB at the crossroads of life and death
    Michael Karin
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0636, USA
    Nat Immunol 3:221-7. 2002
    ..to survive and proliferate in response to infection, whereas those that are self-reactive are eliminated via apoptosis. Even the survival of alloreactive T cells requires their proper costimulation and, when infection subsides, the ..
  85. doi Histone deacetylase inhibitors in cancer therapy
    Andrew A Lane
    Massachusetts General Hospital Cancer Center, Boston, MA 02214, USA
    J Clin Oncol 27:5459-68. 2009
    ..This compaction blocks gene transcription and inhibits differentiation, providing a rationale for developing HDAC inhibitors...
  86. pmc Autophagy in cell death: an innocent convict?
    Beth Levine
    Division of Infectious Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9113, USA
    J Clin Invest 115:2679-88. 2005
    ..This review summarizes the evidence linking autophagy to cell survival and cell death, the complex interplay between autophagy and apoptosis pathways, and the role of autophagy-dependent survival and death pathways in clinical diseases.
  87. pmc A microRNA signature of hypoxia
    Ritu Kulshreshtha
    Molecular Oncology Research Institute, Tufts New England Medical Center, Boston, Massachusetts 02111, USA
    Mol Cell Biol 27:1859-67. 2007
    ..Interestingly, the vast majority of hypoxia-induced microRNAs are also overexpressed in a variety of human tumors...
  88. doi Cytotoxicity and genotoxicity of silver nanoparticles in human cells
    P V AshaRani
    Department of Chemistry, Faculty of Science, National University of Singapore, Singapore 117543, Singapore 117597
    ACS Nano 3:279-90. 2009
    ..Annexin-V propidium iodide (PI) staining showed no massive apoptosis or necrosis...
  89. pmc Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012
    L Galluzzi
    INSERM U848, Apoptosis, Cancer and Immunity, Villejuif, France
    Cell Death Differ 19:107-20. 2012
    ..of distinct cell death morphologies and for the appropriate use of cell death-related terminology, including 'apoptosis', 'necrosis' and 'mitotic catastrophe'...
  90. ncbi Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN
    V Stambolic
    Amgen Institute, and Department of Medical Biophysics, University of Toronto, Ontario, Canada
    Cell 95:29-39. 1998
    ..Expression of exogenous PTEN in mutant cells restores both their sensitivity to agonist-induced apoptosis and normal pattern of PKB/Akt phosphorylation...
  91. ncbi Proliferation, cell cycle and apoptosis in cancer
    G I Evan
    UCSF Cancer Center, 2340 Sutter Street, San Francisco, California 94143-0875, USA
    Nature 411:342-8. 2001
    ..One of these is deregulated cell proliferation, which, together with the obligate compensatory suppression of apoptosis needed to support it, provides a minimal 'platform' necessary to support further neoplastic progression...
  92. ncbi MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells
    C Welch
    Children s Cancer Research Institute and Department of Pediatrics, The University of Texas Health Science Center at San Antonio, MC 7784, TX, USA
    Oncogene 26:5017-22. 2007
    ..Thus, adding to the increasing role of miRNAs in cancer, miR-34a may act as a suppressor of NB tumorgenesis...
  93. ncbi ER stress triggers apoptosis by activating BH3-only protein Bim
    Hamsa Puthalakath
    The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    Cell 129:1337-49. 2007
    ..Bim, a proapoptotic BH3-only member of the Bcl-2 family is required for initiation of apoptosis induced by cytokine deprivation or certain stress stimuli...
  94. 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
    ..functions as a transcriptional activator, and several p53-inducible genes that play a role in the induction of apoptosis in response to p53 have been described...
  95. ncbi Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
    Hannah Farmer
    Cancer Research UK Gene Function and Regulation Group, London, UK
    Nature 434:917-21. 2005
    ..inhibition of PARP enzymatic activity, resulting in chromosomal instability, cell cycle arrest and subsequent apoptosis. This seems to be because the inhibition of PARP leads to the persistence of DNA lesions normally repaired by ..
  96. ncbi The role for endoplasmic reticulum stress in diabetes mellitus
    Decio L Eizirik
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, Route de Lennik, 808 CP 618, 1070 Brussels, Belgium
    Endocr Rev 29:42-61. 2008
    ..acting as beneficial regulators under physiological conditions or as triggers of beta-cell dysfunction and apoptosis under situations of chronic stress. Novel findings suggest that "what makes a beta-cell a beta-cell", i.e...
  97. doi Necroptosis: the release of damage-associated molecular patterns and its physiological relevance
    Agnieszka Kaczmarek
    Molecular Signaling and Cell Death Unit, Department for Molecular Biomedical Research, VIB, 9052 Ghent, Belgium
    Immunity 38:209-23. 2013
  98. ncbi Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors
    X Luo
    Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 75235, USA
    Cell 94:481-90. 1998
    ..The cytochrome c releasing activity of Bid was antagonized by Bcl2. A mutation at the BH3 domain diminished its cytochrome c releasing activity. Bid, therefore, relays an apoptotic signal from the cell surface to mitochondria...
  99. ncbi BCL-2 family members and the mitochondria in apoptosis
    A Gross
    Department of Pathology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 13:1899-911. 1999
  100. ncbi Tumor necrosis factor signaling
    H Wajant
    Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring, Germany
    Cell Death Differ 10:45-65. 2003
    ..In particular, the multiple facets of crosstalk between the various signalling pathways engaged by TNF will be addressed...
  101. pmc The endoplasmic reticulum and the unfolded protein response
    Jyoti D Malhotra
    Howard Hughes Medical Institute, Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, MI 48109, United States
    Semin Cell Dev Biol 18:716-31. 2007
    ..Persistent protein misfolding initiates apoptotic cascades that are now known to play fundamental roles in the pathogenesis of multiple human diseases including diabetes, atherosclerosis and neurodegenerative diseases...

Research Grants75

  1. Genetic variation and regulatory networks: Mechanisms and complexity
    DANA PE ER; Fiscal Year: 2009
    ..These tools will be made publicly available, including a friendly graphical user interface and visualization. ..
  2. NIH Director's Pioneer Award
    Junying Yuan; Fiscal Year: 2009
    ..No Abstract provided ..
  3. Anti-tumor properties of curcumin in oral cancers: role of thioredoxin reductase
    STEPHEN WILLIAM TUTTLE; Fiscal Year: 2010
    ..reductase 1 (TxRd1), is an essential selenoprotein with defined roles in redox regulation of cell growth, death (apoptosis), transcription, DNA repair, and angiogenesis...
  4. The Primate Corpus Luteum: Functional Regression and Cardiovascular Impacts
    Randy L Bogan; Fiscal Year: 2012
    ..endogenous LXR ligand levels, and lipid localization will provide an assessment of RCT activity, and markers of apoptosis will evaluate CL structural integrity...
  5. Role of NGF in inflammatory and proliferative cascades of psoriatic disease
    Siba P Raychaudhuri; Fiscal Year: 2012
    ..on synovial tissue pathophysiology will be elucidated by examining the effect of NGF/NGF-R on proliferation and apoptosis of FLS...
  6. Cross-talk Between Coagulation, Inflammation, and Immunity
    Lawrence L Leung; Fiscal Year: 2013
    ..cell signaling by OPN-R in comparison to OPN-FL and OPN-L in terms of cell adhesion, cell proliferation, apoptosis, protein phosphorylation, gene expression and cytokine production...
  7. Prevention of Acute Lung Injury by IL-6 activated STAT3
    Ana Moran; Fiscal Year: 2010
    ..Lung alveolar epithelial cell (AEC) injury and apoptosis are cardinal features of ALI;an improved understanding of this process in T/HS- induced lung injury is needed in ..
  8. Qinghua Sun; Fiscal Year: 2015
    ..Fat tissues will also be assessed for PERK-mediated UPR pathway on mitochondrial function, inflammation and apoptosis. PM2.5 with Nickel or PM2.5 with vanadium will be compared to PM2...
  9. FASEB SRC on Lysophospholipd Mediators in Health and Disease
    Julie D Saba; Fiscal Year: 2011
    ..LPA and S1P regulate chemotaxis, stress responses, cytoskeletal organization, calcium signaling, cell survival, apoptosis, autophagy, and gene transcription...
  10. A Hybrid PARP Inhibitor and Redox Catalyst for Lung Transplantation
    GARRY JOHN SOUTHAN; Fiscal Year: 2012
    ..of neutrophil infiltration, lipid peroxidation, protein nitrosation, vascular permeability, PARP activation, and apoptosis) and arterial oxygenation;and 2) bronchoalveolar lavage markers of pulmonary injury (levels of neutrophil ..
  11. Development of a Nonpsychotropic Cannabinoid Agonist for the Treatment of Sclerod
    Robert B Zurier; Fiscal Year: 2012
    ..Because myofibroblasts enhance the stiffness of the ECM, produce profibrotic cytokines, and are resistant to apoptosis, their accumulation in tissue is believed to promote progression of fibrosis...
  12. Role of SAMe on UBC9 and sumolyation in liver cancer and alcoholic liver injury
    Maria Lauda Tomasi; Fiscal Year: 2012
    ..UBC9 function in MCF-7 breast cancer cells transplanted in nude mice inhibited cell growth and increased apoptosis via Bcl-2 dependent mechanisms...
  13. Pathogenesis and Treatment of Liver Disease in Transaldolase Deficiency
    Andras Perl; Fiscal Year: 2013
    ..cells exhibited mitochondrial dysfunction, increased susceptibility to H2O 2 and resistance to Fas apoptosis. To create an animal model of TAL deficiency, we inactivated the TALDO1 genomic locus in the mouse...
  14. ANTHONY JOHN KANAI; Fiscal Year: 2016
    ..This leads to swelling and rupture of the mitochondria, cytochrome c release and apoptosis. We developed a mitochondrial targeting strategy (U.S...
  15. CLIFFORD RUSSELL GREYSON; Fiscal Year: 2016
    ..spectrin, 1-actinin or titin;modification of regulatory proteins such as troponin-I, troponin-T;or initiation of apoptosis. The overall goal of this project is to identify the mechanism by which acute RV pressure overload causes ..
  16. A Redox-active PARP Inhibitor for Lung Transplantation
    ANDREW LURIE SALZMAN; Fiscal Year: 2012
    ..by histology, levels of PMN infiltration, lipid peroxidation, NF-?B, protein nitrosation, PARP-1 activation, apoptosis, and oxygenation (PaO2)...
  17. Stephen E McGowan; Fiscal Year: 2016
    ..are initiated by PDGFs, are mediated by Abelson kinase and Rac1, and alter pericyte or LF proliferation and apoptosis will be examined...
  18. The role of Fli1 in T cell function and the pathogenesis of lupus
    Tamara K Nowling; Fiscal Year: 2011
    ..We propose to study cell proliferation, apoptosis and suppressor and effector functions of T cells in mice expressing reduced Fli1 activity and to identify the ..
  19. Bradley P Dixon; Fiscal Year: 2014
    ..under a hyperosmolal bladder microenvironment, and to evaluate the activation of cell cycle checkpoints and apoptosis following DNA damage within a hyperosmolal bladder microenvironment...
  20. Targeted siRNA nanotechnology for intravesical treatment of urologicaldiseases
    Robert M Weiss; Fiscal Year: 2010
    ..The Inhibitor of Apoptosis (IAP), survivin, is not detected in normal urothelium and its expression in bladder cancer correlates with poor ..
  21. Translational Machinery in Stress Signaling and Tumor Suppression
    THOMAS J contact BEGLEY; Fiscal Year: 2010
    ..TRM9 is required for regulating the levels of proteins that promote growth arrest, repair damage and/or induce apoptosis, thus placing TRM9 in a tumor suppressive / growth inhibitory role after environmental stress...
  22. Targeting Inflammation for the Amelioration of Cisplatin-Hearing Loss
    Vickram Ramkumar; Fiscal Year: 2011
    ..Other treatment approaches target proteins involved in apoptosis which contribute to death of outer hair cells (OHCs)...
  23. Terence S Dermody; Fiscal Year: 2015
    ..The als protein is required for reovirus dissemination and mediates cell-cycle arrest and apoptosis induction...
  24. Robert T Means; Fiscal Year: 2014
    ..the role of Epo concentration in hepcidin effects on erythropoiesis;C., the role of apoptosis/anti-proliferation in inhibitory effects of hepcidin on erythropoiesis;D...
  25. Trichothecene Toxicity and the Ribotoxic Stress Response
    James J Pestka; Fiscal Year: 2012
    ..ricin, Shiga toxin, anisomycin) induce proinflammatory gene expression and apoptosis in lymphoid tissues...
  26. Retinoid Metabolism and Alcohol Induced Disease
    William S Blaner; Fiscal Year: 2010
    ..potent transcriptional regulators that are needed for mediating normal cell proliferation, differentiation and apoptosis. One adverse action of alcohol involves promotion of tissue and organ damage by impairing retinoid metabolism ..
  27. Junxuan Lu; Fiscal Year: 2014
    ..type, androgen dependent) and DU145 (mutant p53, androgen independent) PCa cells as well as caspase- mediated apoptosis involving reactive oxygen species (ROS)...
  28. A Hybrid Katp Channel Opener to Prevent Radiocontrast-Induced Nephropathy
    Kanneganti Murthy; Fiscal Year: 2012
    ..histology score), lipid peroxidation (malondialdehyde, F21-isoprostane), PMN infiltration (myeloperoxidase), apoptosis (TUNEL staining), 3-nitrotyrosine (a measure of ONOO- formation), poly(ADP-ribose) (a measure of PARP activity);..
  29. Rajvir Dahiya; Fiscal Year: 2015
    ..Alterations in cell growth will be assessed by monitoring cell proliferation, cell cycle distribution, apoptosis and in vitro invasion...
    RUTH M STEWARD; Fiscal Year: 2010
    ..PDCD2 was originally identified in mammalian cells as an apoptosis-associated gene, but our results suggest that also in vertebrates it is associated with cell proliferation...
  31. Regulation of epithelial cell homeostasis by actin microfilaments
    Seema Khurana; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): The homeostatic balance between proliferation and apoptosis is essential for the intestinal epithelium to function as a physiological and structural barrier...
  32. ANIL KUMAR JAISWAL; Fiscal Year: 2014
    ..The domain deletion, transfection, immunoprecipitation, Western analysis, reporter and apoptosis assays will be used in these studies...
  33. Role of the Mammalian Siderophore in Cellular Iron Metabolism and Erythropoiesis
    Laxminarayana R Devireddy; Fiscal Year: 2012
    ..transport a variety of ligands and function in disparate biological processes ranging from vitamin delivery to apoptosis. We originally discovered 24p3 as the gene undergoing maximum transcriptional stimulation following induction of ..
  34. DHAN V KALVAKOLANU; Fiscal Year: 2014
    ..factor known to regulate cell differentiation, energy metabolism, immune response, tumor growth and apoptosis. A gene expression micro- array analysis in our lab identified several IFN regulated genes, whose expression ..
  35. Combination drug treatment to inhibit multiple cell death pathways after TBI
    ALAN IRA FADEN; Fiscal Year: 2010
    ..LFP)- cell death in the central core region also includes a substantial component of caspase-independent apoptosis, whereas the better known caspase-dependent cell death is detected in the more peripheral regions where ATP and ..
  36. Enzymatic Regulation of S-Glutathionylation : Role in Apoptosis and Disease
    John J Mieyal; Fiscal Year: 2012
    ..in signaling pathways that govern whether a cell survives chemical insults or commits to programmed cell death (apoptosis). Concomitant with the L-DOPA-induced deficiency in these enzymes, there is an increase in neuron cell death...
  37. Xianglin Shi; Fiscal Year: 2015
    ..and TNF1 activation/expression, neoplastic transformation, cancer cell migration and invasion, and induction of apoptosis in HL60 cells...
  38. ICSBP Function During Myeloid Differentiation
    ELIZABETH ANN EKLUND; Fiscal Year: 2011
    ..However, ICSBP-deficient myeloid progenitor cells exhibit resistance to apoptosis, hypersensitivity to hematopoietic cytokines, and the tendency to accumulate additional genetic lesions...
  39. MATTHEW PETER COGGINS; Fiscal Year: 2014
    ..IKKB, 2) IKKB promotes normal CM function through modulation of calcium cycling, and 3) IKKB inhibits CM apoptosis in most settings through regulation of NF-kB dependent transcription...
  40. Protein Nitration in the Placenta
    Leslie Myatt; Fiscal Year: 2012
    ..In preeclampsia there is mitochondrial dysfunction and increased trophoblast apoptosis, via downregulation of anti-apoptotic proteins including Bcl-2 and up-regulation of pro-apoptotic p53...
  41. A Thioredoxin Mimetic for Radiocontrast Nephropathy
    GARRY JOHN SOUTHAN; Fiscal Year: 2012
    ..protection, as manifested by renal levels of necrosis (histology), lipid peroxidation, neutrophil infiltration, apoptosis, necrosis, peroxynitrite and poly(ADP- ribose) formation, and serum concentrations of neutrophil gelatinase-..
  42. Mahin D Maines; Fiscal Year: 2015
    ..activation of kinases in the insulin/IGF/MAPK/PI3K signaling pathways that regulate glucose uptake, cell growth, apoptosis and stress-response gene expression (c-fos, c-jun, HO-1, CREB/ATF- 2)...
  43. ER stress: role in myocyte apoptosis and myocardial remodeling
    Krishna Singh; Fiscal Year: 2013
    ..Increased sympathetic activity is a central feature in patients with heart failure. Cardiac myocyte loss due to apoptosis plays an important role in the progression of heart failure...
  44. Hybrid Katp Channel Opener and Redox Catalyst for Lung Transplantation
    Prakash Jagtap; Fiscal Year: 2013
    ..histologic score, PMN infiltration, lipid peroxidation, protein nitrosation, PARP-1 activation, nuclear NF-kB, apoptosis, and oxygenation (PaO2)...
  45. DANIEL J CARR; Fiscal Year: 2015
    ..there is a massive loss of cells residing in the draining lymph node associated with an increase in T cell apoptosis and necrosis...
  46. Sirtuin/FOXO Signaling in the Regulation of Bone Mass
    Stavroula Kousteni; Fiscal Year: 2012
    ..FOXO1, one of the three FOXO homologs, regulates cell differentiation, promotes either cell survival or apoptosis;and also increases lifespan in model biologic systems...
  47. JoAnn Sekiguchi; Fiscal Year: 2014
    ..strand breaks, and it is required for activation of cell cycle checkpoints, direct DNA repair events and/or apoptosis. ATM also plays important roles in the control of oxidative stress, and ATM deficiency leads to increased levels ..
  48. Twenty-second Annual Fanconi Anemia Research Fund Scientific Symposium
    GROVER CARLTON BAGBY; Fiscal Year: 2010
    ..the importance of Fanconi anemia genes in tumor suppression, DNA repair, stem cell function, and suppression of apoptosis and senescence, survival, leukemogenesis and carcinogenesis, and genetic instability - topics highly relevant to ..
    ..Antiestrogen resistance will be measured by quantifying apoptosis and proliferation of the breast cancer cells after treatment with tamoxifen and fulvestrant...
  50. Gene Therapy with Cardiotropic Vectors for the Treatment of Heart Failure
    Roger J Hajjar; Fiscal Year: 2013
    ..The normal myocytes that remain are under continuous stress from hormonal and physical stimuli that can induce apoptosis and cell death or render them dysfunctional...
  51. 24th Annual Fanconi Anemia Research Fund Scientific Symposium
    GROVER CARLTON BAGBY; Fiscal Year: 2012
    ..the importance of Fanconi anemia genes in tumor suppression, DNA repair, stem cell function, and suppression of apoptosis and senescence;thus, advances made in FA science have an impact beyond patients and families affected by this ..
  52. Role of Mitochondria in the Regulation of Iron metabolism by Alcohol
    ..Mitochondria play a key role in apoptosis and alcohol-mediated changes in mitochondria induce apoptotic stimuli...
  53. Mechanism-Based Discovery of Protectants Against Iron-Dependant Oxidative Injury
    JUSTIN M SCHWARTZ; Fiscal Year: 2011
    ..after reintroduction of oxygenated blood to ischemic tissue is a major precipitating event causing necrosis and apoptosis in I/R injury...
  54. Remote-control mouse-implantable micropumps for establishment of regenerative cap
    JUAN GABRIEL contact SANTIAGO; Fiscal Year: 2010
    ..readouts will be: 1) bioluminescence to quantify the proliferative response;2) histology to quantify fibrosis, apoptosis, and the phenotypes of the cells producing the bioluminescence signal;and, 3) functional assays to measure ..
  55. Arsenic Trioxide and Acute Myeloid Leukemia
    Yongkui Jing; Fiscal Year: 2012
    ..We and others determined that, through generation of reactive oxygen species (ROS), As2O3 induced apoptosis of APL cells...
  56. Ceramide Metabolism and Photoreceptor Homeostasis
    Usha R Acharya; Fiscal Year: 2013
    ..them like ceramide, sphingosine 1-phosphate are also bioactive lipids regulating cellular functions ranging from apoptosis to angiogenesis...
  57. ELIZABETH ANN EKLUND; Fiscal Year: 2016
    ..We identified an Icsbp-target-gene set that is enriched for genes which control Fas-induced apoptosis and/or bcatenin activity...
  58. Genetic Studies of Optic Atrophy
    Taosheng Huang; Fiscal Year: 2012
    ..We will analyze the mutants for apoptosis in eye phenotypes and test the effectiveness of caspase inhibitor in reversing rough eye phenotypes...
  59. Cell signaling as a leukemia biomarker
    ..factor that alters differentiation, and 2) in a signaling pathway protein that affects cell proliferation and/or apoptosis. A significant component of cell signaling involves phosphorylation/de-phosphorylation cycles on pathway ..
  60. TIMOTHY L SITA; Fiscal Year: 2016
    ..This epigenetic silencing of MGMT activity allows TMZ to induce apoptosis in glioblastoma cells and drastically increases survival in GBM patients...
  61. Targeting Cell Death to Prevent Ventricular Remodeling and Heart Failure
    Abhinav Diwan; Fiscal Year: 2011
    ..is inevitable due to oxygen/nutrient deprivation, but is followed by a wave of cell-autonomous death, or apoptosis, in the peri-infarct region...
  62. The Role of Interleukin-10 During Fatal Alphavirus Encephalomyelitis
    KIRSTEN KULCSAR; Fiscal Year: 2013
    ..IL-10 can also directly protect neurons from apoptosis in models of glutamate excitotoxicity and other stress conditions...
  63. Androgen Modulation of Neurodegeneration in Dopamine Neurons
    Rebecca L Cunningham; Fiscal Year: 2010
    ..It is believed that the underlying mechanism of PD involves oxidative stress leading to cellular apoptosis. In many peripheral cells and some neuronal cells, androgens have been shown to increase apoptosis...
  64. Apoptosis and Trophoblast Fusion
    NEAL STEWART ROTE; Fiscal Year: 2010
    ..Our preliminary data suggest that several apoptosis-related proteins, particularly caspases 3, 8, and 14, may be critical participants in trophoblast ..
    Hasan Mukhtar; Fiscal Year: 1999
    ..Now, the first two aims will address the relevance of apoptosis in PcPDT...
  66. Extracellular ubiquitin: role in myocyte apoptosis and myocardial remodeling
    Krishna Singh; Fiscal Year: 2010
    ..Stimulation of ? adrenergic receptor (?-AR), specifically ?1-AR, increases cardiac myocyte apoptosis in vitro and in vivo, while stimulation of ?2-AR plays an anti-apoptotic role in ?-AR-stimulated apoptosis...
    Robert Strange; Fiscal Year: 2004
    Breast cancer can result from excessive proliferation and/or insufficient apoptosis of mammary epithelium. During a woman's life, the breast undergoes dramatic developmental changes with associated changes in proliferation and apoptosis...
  68. Bcl-2, A Key Factor for Dentinogenesis and Tooth Damage Repair
    Wenjian Zhang; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Apoptosis has been identified in various cellular compartments of developing teeth and in teeth damaged by bacterial infection or operative procedures...
  69. Screening for Chemicals that Potentiate TRAIL-Induced Apoptosis of Cancer Cells
    DMITRI ROZANOV; Fiscal Year: 2007
    ..of this R03 application is to describe our proposed drug design effort designed to potentiate TRAIL-induced apoptosis in cancer cells...
    David Li; Fiscal Year: 2000
    ..or without insult by oxidative stress, calcimycin and UVB consistently suggest that induced lens epithelial cell apoptosis is such a common cellular mechanism...
  71. Role of ATM in Cardiac Myocyte Loss and Myocardial Remodeling
    Krishna Singh; Fiscal Year: 2009
    ..is suggested to be a key regulator of signaling cascades involved in cell cycle checkpoints, DNA repair and apoptosis. Evidence has been provided that inhibition of ATM induces a switch from apoptosis to necrosis in murine ..
    V Broaddus; Fiscal Year: 2001
    DESCRIPTION: Pleural mesothelial cells, the progenitor of the asbestos-induced tumor mesothelioma, undergo apoptosis when exposed to asbestos...
  73. Modulation of Glucocorticoid-Evoked Lymphocyte Apoptosis by BTG1
    RHEEM MEDH; Fiscal Year: 2007
    unreadable] DESCRIPTION (provided by applicant): A process of suicidal cell death, termed apoptosis, is vital for normal physiology because it regulates cellular turnover and preserves tissue vitality...
  74. IGF binding protein-3 in beta cell apoptosis
    ROBERT FERRY JR; Fiscal Year: 2005
    Autoimmune and non-immune apoptosis, or programmed death, of pancreatic beta cells results in type 1 diabetes mellitus...