Cflar

Summary

Gene Symbol: Cflar
Description: CASP8 and FADD-like apoptosis regulator
Alias: 2310024N18Rik, A430105C05Rik, CLARP, Cash, Casper, FLAME, FLAME-1, Flip, Gm9845, I-FLICE, MRIT, c-Flip, CASP8 and FADD-like apoptosis regulator, FADD-like antiapoptotic molecule 1, MACH-related inducer of toxicity, caspase homolog, caspase-eight-related protein, caspase-like apoptosis regulatory protein, cellular FLICE-like inhibitory protein, inhibitor of FLICE, usurpin
Species: mouse

Top Publications

  1. ncbi CTLA-4-/- mice display T cell-apoptosis resistance resembling that ascribed to autoimmune-prone non-obese diabetic (NOD) mice
    M L Bergman
    Department of Cell and Molecular Biology, University of Umea, S 901 87 Umeå Sweden
    J Autoimmun 16:105-13. 2001
  2. doi The death receptor antagonist FLIP-L interacts with Trk and is necessary for neurite outgrowth induced by neurotrophins
    Rana S Moubarak
    Institut de Neurociencies, Departament de Bioquimica i Biologia Molecular, Facultat de Medicina, Universitat Autonoma de Barcelona, Campus de Bellaterra Edifici M, 08193 Bellaterra, Spain
    J Neurosci 30:6094-105. 2010
  3. ncbi CASH, a novel caspase homologue with death effector domains
    Y V Goltsev
    Department of Membrane Research and Biophysics, Weizmann Institute of Science, 76100 Rehovot, Israel
    J Biol Chem 272:19641-4. 1997
  4. ncbi Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally
    E E Varfolomeev
    Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel
    Immunity 9:267-76. 1998
  5. ncbi Inhibition of death receptor signals by cellular FLIP
    M Irmler
    Institute of Biochemistry, Lausanne Branch, University of Lausanne, Switzerland
    Nature 388:190-5. 1997
  6. ncbi Requirement for Casper (c-FLIP) in regulation of death receptor-induced apoptosis and embryonic development
    W C Yeh
    Amgen Institute, Department of Medical Biophysics, University of Toronto and Ontario Cancer Institute, Canada
    Immunity 12:633-42. 2000
  7. doi Nuclear localization of c-FLIP-L and its regulation of AP-1 activity
    Jing Zhang
    Jiangsu Center of Hepatobiliary Diseases and the State Key Laboratory of Pharmaceutical Biotechnology, Affiliated Gulou Hospital, School of Life Sciences, Nanjing University, Nanjing, China
    Int J Biochem Cell Biol 41:1678-84. 2009
  8. pmc Catalytic activity of the caspase-8-FLIP(L) complex inhibits RIPK3-dependent necrosis
    Andrew Oberst
    Dept of Immunology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Nature 471:363-7. 2011
  9. doi Ablation of c-FLIP in hepatocytes enhances death-receptor mediated apoptosis and toxic liver injury in vivo
    Jörn M Schattenberg
    Department of Medicine, University Medical Center, Johannes Gutenberg University, 55101 Mainz, Germany
    J Hepatol 55:1272-80. 2011
  10. ncbi Influence of TRP53 status on FAS membrane localization, CFLAR (c-FLIP) ubiquitinylation, and sensitivity of GC-2spd (ts) cells to undergo FAS-mediated apoptosis
    Yamini Chandrasekaran
    College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712 0125, USA
    Biol Reprod 74:560-8. 2006

Scientific Experts

  • Claudia Giampietri
  • Jörn Schattenberg
  • Jerzy M Behnke
  • Jiyan Zhang
  • Yujiang Fang
  • You Wen He
  • Christopher P Dillon
  • Ricardo Weinlich
  • Douglas R Green
  • Nu Zhang
  • Qi Quan Huang
  • Rana S Moubarak
  • Andrew Oberst
  • Joan X Comella
  • Vivian Tseveleki
  • Laura J Janke
  • Xue Wang
  • Jorge Urresti
  • Kishu Ranjan
  • Yu Jung Wu
  • E S Marini
  • Jennifer Q Russell
  • Hideo Yagita
  • Ralph C Budd
  • N Gehrke
  • F Ewald
  • Era Taoufik
  • Lesley Probert
  • Y W He
  • Kim Newton
  • Jessica M Haverkamp
  • Prajwal Gurung
  • Diego A Rodriguez
  • Sangchul Lee
  • Nadine Wittkopf
  • Junmei Ye
  • Tanja Telieps
  • M X He
  • Stephanie Reix
  • Richard M Pope
  • Zan Huang
  • Robert Birkett
  • Harris Perlman
  • Jinfeng Xiao
  • Lukas Bossaller
  • Kari Högstrand
  • D M Moujalled
  • Xuehua Piao
  • Regina Golan-Gerstl
  • N Vanlangenakker
  • David Llobet
  • Rong Hua Tao
  • I Schmitz
  • Claire Gordy
  • Fabrizio Antonangeli
  • Eun Jung Lim
  • Francis Coffey
  • Yi Chen Lin
  • J Huo
  • J Y Zhu
  • Yu Yu
  • Eileen D Vesely
  • Youngmi Kim
  • Ko Okumura
  • Hiroyasu Nakano
  • Haibing Zhang
  • Sachiko Komazawa-Sakon
  • Carme Sole
  • John H Richburg
  • N Ueffing
  • Kaycie Hopkins
  • Jennifer Hinshaw-Makepeace
  • Daniel R Prows
  • Anice Moumen
  • Gaël Roué
  • Ravi S Misra
  • Shinji Takai
  • Martina Buck
  • M Schuchmann
  • Yamini Chandrasekaran
  • Stefan W Ryter
  • Lufen Chang
  • Akihito Nakajima
  • Su He Wang
  • Augustine M K Choi
  • Hong Pyo Kim
  • Yong Wang
  • Yasuhiko Matsumori
  • Hans Lassmann
  • Atticus H Hainsworth

Detail Information

Publications89

  1. ncbi CTLA-4-/- mice display T cell-apoptosis resistance resembling that ascribed to autoimmune-prone non-obese diabetic (NOD) mice
    M L Bergman
    Department of Cell and Molecular Biology, University of Umea, S 901 87 Umeå Sweden
    J Autoimmun 16:105-13. 2001
    ..This reinforces the notion that CTLA-4 contributes to the pathogenesis of autoimmune diabetes...
  2. doi The death receptor antagonist FLIP-L interacts with Trk and is necessary for neurite outgrowth induced by neurotrophins
    Rana S Moubarak
    Institut de Neurociencies, Departament de Bioquimica i Biologia Molecular, Facultat de Medicina, Universitat Autonoma de Barcelona, Campus de Bellaterra Edifici M, 08193 Bellaterra, Spain
    J Neurosci 30:6094-105. 2010
    FLICE-inhibitory protein (FLIP) is an endogenous inhibitor of the signaling pathway triggered by the activation of death receptors...
  3. ncbi CASH, a novel caspase homologue with death effector domains
    Y V Goltsev
    Department of Membrane Research and Biophysics, Weizmann Institute of Science, 76100 Rehovot, Israel
    J Biol Chem 272:19641-4. 1997
    ..We report cloning of two splice variants of a novel protein, CASH, that contain two N-terminal death effector domains and can bind through them to each other, to MORT1/FADD, to CASP-..
  4. ncbi Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally
    E E Varfolomeev
    Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel
    Immunity 9:267-76. 1998
    ..These findings indicate that Caspase 8 plays a necessary and nonredundant role in death induction by several receptors of the TNF/NGF family and serves a vital role in embryonal development...
  5. ncbi Inhibition of death receptor signals by cellular FLIP
    M Irmler
    Institute of Biochemistry, Lausanne Branch, University of Lausanne, Switzerland
    Nature 388:190-5. 1997
    ..Here we report the characterization of an inhibitor of apoptosis, designated FLIP (for FLICE-inhibitory protein), which is predominantly expressed in muscle and lymphoid tissues...
  6. ncbi Requirement for Casper (c-FLIP) in regulation of death receptor-induced apoptosis and embryonic development
    W C Yeh
    Amgen Institute, Department of Medical Biophysics, University of Toronto and Ontario Cancer Institute, Canada
    Immunity 12:633-42. 2000
    b>Casper (c-FLIP) associates with FADD and caspase-8 in signaling complexes downstream of death receptors like Fas. We generated Casper-deficient mice and cells and noted a duality in the physiological functions of this molecule...
  7. doi Nuclear localization of c-FLIP-L and its regulation of AP-1 activity
    Jing Zhang
    Jiangsu Center of Hepatobiliary Diseases and the State Key Laboratory of Pharmaceutical Biotechnology, Affiliated Gulou Hospital, School of Life Sciences, Nanjing University, Nanjing, China
    Int J Biochem Cell Biol 41:1678-84. 2009
    Cellular FLICE-like inhibitory protein (c-FLIP-L), similar in structure to caspase-8, is capable of blocking Fas- or other death receptors (DR)-mediated apoptosis through association with FADD in the DISC...
  8. pmc Catalytic activity of the caspase-8-FLIP(L) complex inhibits RIPK3-dependent necrosis
    Andrew Oberst
    Dept of Immunology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Nature 471:363-7. 2011
    ..RIPK3-dependent necrosis without inducing apoptosis by functioning in a proteolytically active complex with FLICE-like inhibitory protein long (FLIP(L), also known as CFLAR), and this complex is required for the protective function.
  9. doi Ablation of c-FLIP in hepatocytes enhances death-receptor mediated apoptosis and toxic liver injury in vivo
    Jörn M Schattenberg
    Department of Medicine, University Medical Center, Johannes Gutenberg University, 55101 Mainz, Germany
    J Hepatol 55:1272-80. 2011
    ..Although extensively studied, the intracellular signaling events in hepatocytes are only incompletely understood...
  10. ncbi Influence of TRP53 status on FAS membrane localization, CFLAR (c-FLIP) ubiquitinylation, and sensitivity of GC-2spd (ts) cells to undergo FAS-mediated apoptosis
    Yamini Chandrasekaran
    College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712 0125, USA
    Biol Reprod 74:560-8. 2006
    ..TRP53 may influence the ubiquitinylation and consequent proteosomal degradation of a negative regulator of FAS, CFLAR (L) (c-FLIP [L]), in human colon cancer cells...
  11. doi Increased hepatic fibrosis and JNK2-dependent liver injury in mice exhibiting hepatocyte-specific deletion of cFLIP
    Jörn M Schattenberg
    Department of Medicine, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
    Am J Physiol Gastrointest Liver Physiol 303:G498-506. 2012
    ..CCl(4)) and thioacetamide (TAA) were examined in mice exhibiting a hepatocyte-specific deletion of cFLIP (flip(-/-)). Acute liver injury from CCl(4) and TAA were enhanced in flip(-/-) mice...
  12. doi Testis atrophy and reduced sperm motility in transgenic mice overexpressing c-FLIP(L)
    Fabrizio Antonangeli
    Department of Histology and Medical Embryology, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, Italy
    Fertil Steril 93:1407-14. 2010
    To study the effect of c-FLIP overexpression in testicular germ cells.
  13. ncbi Cellular FLIP (long isoform) overexpression in T cells drives Th2 effector responses and promotes immunoregulation in experimental autoimmune encephalomyelitis
    Vivian Tseveleki
    Laboratory of Molecular Genetics, Hellenic Pasteur Institute, National Center for Scientific Research Demokritos, Athens, Greece
    J Immunol 173:6619-26. 2004
    Cellular FLIP (c-FLIP) is an endogenous inhibitor of death receptor-induced apoptosis through the caspase 8 pathway...
  14. pmc Myeloid-derived suppressor activity is mediated by monocytic lineages maintained by continuous inhibition of extrinsic and intrinsic death pathways
    Jessica M Haverkamp
    Department of Infectious Diseases, St Jude Children s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA Department of Immunology, St Jude Children s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA
    Immunity 41:947-59. 2014
    ..pathways, we found the monocytic suppressor-cell subset, but not the granulocytic subset, requires continuous c-FLIP expression to prevent caspase-8-dependent, RIPK3-independent cell death...
  15. ncbi Expression of FADD and cFLIPL balances mitochondrial integrity and redox signaling to substantiate apoptotic cell death
    Kishu Ranjan
    Department of Cell Biology, School of Biological Sciences and Biotechnology, Indian Institute of Advanced Research, Koba Institutional Area, Gandhinagar, Gujarat, 382007, India
    Mol Cell Biochem 422:135-150. 2016
    ..Altogether, our findings suggest that FADD and cFLIPL are important modulators of mitochondrial-associated apoptosis apart from the death receptor signaling...
  16. pmc Lifeguard Inhibits Fas Ligand-mediated Endoplasmic Reticulum-Calcium Release Mandatory for Apoptosis in Type II Apoptotic Cells
    Jorge Urresti
    From the Cell Signaling and Apoptosis Group and the Institut de Neurociències, Departament de Bioquimica i Biologia Molecular, Facultat de Medicina, Universitat Autonoma de Barcelona, 08193 Bellaterra, Spain
    J Biol Chem 291:1221-34. 2016
    ..On the basis of our observations, we propose that there is a required step in the induction of type II apoptotic cell death that involves calcium mobilization from the ER and that this step is modulated by LFG. ..
  17. doi Cellular FLIP Inhibits Myeloid Cell Activation by Suppressing Selective Innate Signaling
    Yu Jung Wu
    Institute of Immunology, National Taiwan University, Taipei 10051, Taiwan, Republic of China Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan, Republic of China and
    J Immunol 195:2612-23. 2015
    Cellular FLIP (c-FLIP) specifically inhibits caspase-8 and suppresses death receptor-induced apoptosis. c-FLIP has also been reported to transmit activation signals...
  18. pmc CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis
    Qi Quan Huang
    Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA
    Nat Commun 6:7086. 2015
    Dendritic cells (DCs) are critical for immune homeostasis. To target DCs, we generated a mouse line with Flip deficiency in cells that express cre under the CD11c promoter (CD11c-Flip-KO)...
  19. pmc PMLRARα binds to Fas and suppresses Fas-mediated apoptosis through recruiting c-FLIP in vivo
    Rong Hua Tao
    Departments of Lymphoma and Myeloma, The University of Texas M D Anderson Cancer Center, Houston, TX, USA
    Blood 118:3107-18. 2011
    ..was demonstrated in U937/PR9 cells, human APL cells and transgenic mouse APL cells, in which PMLRARα recruited c-FLIP(L/S) and excluded procaspase 8 from Fas death signaling complex...
  20. pmc TNF-induced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members
    N Vanlangenakker
    Department for Molecular Biomedical Research, VIB, Zwijnaarde Ghent, Belgium
    Cell Death Dis 2:e230. 2011
    ..Finally, we also report RIP1-independent but RIP3-mediated necroptosis in the context of TNF signaling in particular conditions...
  21. pmc In mouse embryonic fibroblasts, neither caspase-8 nor cellular FLICE-inhibitory protein (FLIP) is necessary for TNF to activate NF-κB, but caspase-8 is required for TNF to cause cell death, and induction of FLIP by NF-κB is required to prevent it
    D M Moujalled
    La Trobe Institute for Molecular Science, La Trobe University, Kingsbury Drive, Bundoora, VIC 3086, Australia
    Cell Death Differ 19:808-15. 2012
    ..To determine the roles of FLICE-inhibitory protein (FLIP) and caspase-8 in TNF-induced activation of NF-κB and apoptosis, we used mouse embryonic fibroblasts derived from ..
  22. pmc The endogenous caspase-8 inhibitor c-FLIPL regulates ER morphology and crosstalk with mitochondria
    E S Marini
    Istituto Pasteur Fondazione Cenci Bolognetti, DAHFMO Section of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy
    Cell Death Differ 22:1131-43. 2015
    ..In this study, we report that the long isoform of the cellular FLICE-inhibitory protein (c-FLIP(L)), a well-known inhibitor of the extrinsic cell death initiator caspase-8, localizes at the endoplasmic reticulum ..
  23. doi Cellular FLICE-like inhibitory protein deviates myofibroblast fas-induced apoptosis toward proliferation during lung fibrosis
    Regina Golan-Gerstl
    Lung Cellular and Molecular Laboratory, Institute of Pulmonary Medicine, Hadassah University Hospital, POB 12000, Jerusalem, Israel
    Am J Respir Cell Mol Biol 47:271-9. 2012
    ..Cellular FLICE-like inhibitory protein (c-FLIP) is a regulator of cell death receptor-induced apoptosis in many cell types...
  24. pmc Acute organ failure following the loss of anti-apoptotic cellular FLICE-inhibitory protein involves activation of innate immune receptors
    N Gehrke
    I Department of Medicine, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
    Cell Death Differ 22:826-37. 2015
    ..These results encourage the development of organ-specific anti-apoptotic and anti-inflammatory therapies in acute organ failure. ..
  25. pmc Cutting edge: FAS (CD95) mediates noncanonical IL-1β and IL-18 maturation via caspase-8 in an RIP3-independent manner
    Lukas Bossaller
    Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    J Immunol 189:5508-12. 2012
    ..Hence, Fas controls a novel noncanonical IL-1β activation pathway in myeloid cells, which could play an essential role in inflammatory processes, tumor surveillance, and control of infectious diseases...
  26. pmc A pathway involving HDAC5, cFLIP and caspases regulates expression of the splicing regulator polypyrimidine tract binding protein in the heart
    Junmei Ye
    Departament de Ciencies Mediques Basiques, Universitat de Lleida IRBLLEIDA, Av Rovira Roure, 80, Lleida, 25198 Spain
    J Cell Sci 126:1682-91. 2013
    ....
  27. doi Cellular FLICE-like inhibitory protein secures intestinal epithelial cell survival and immune homeostasis by regulating caspase-8
    Nadine Wittkopf
    Department of Medicine 1, Friedrich Alexander University, Erlangen, Germany
    Gastroenterology 145:1369-79. 2013
    ..Dysregulation of epithelial cell death has been implicated in barrier dysfunction and in the pathogenesis of intestinal inflammation. We investigated mechanisms of cell-death regulation in the intestinal epithelium of mice...
  28. pmc Protective roles for caspase-8 and cFLIP in adult homeostasis
    Ricardo Weinlich
    Department of Immunology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Cell Rep 5:340-8. 2013
    ..Furthermore, RIPK3-dependent inflammation is dispensable for the skin phenotype. ..
  29. doi Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis
    Kim Newton
    Department of Physiological Chemistry, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA
    Science 343:1357-60. 2014
    ..Our data indicate that the kinase activity of RIPK3 is essential for necroptosis but also governs whether a cell activates caspase-8 and dies by apoptosis. ..
  30. doi Constitutive expression of murine c-FLIPR causes autoimmunity in aged mice
    F Ewald
    1 Institute of Molecular and Clinical Immunology, Otto von Guericke University Magdeburg, Leipziger Str 44, Magdeburg, Germany 2 Research Group of Systems Oriented Immunology and Inflammation Research, Department of Immune Control, Helmholtz Centre for Infection Research, Inhoffenstr 7, Braunschweig, Germany
    Cell Death Dis 5:e1168. 2014
    ..The only short murine c-FLIP splice variant is c-FLIPRaji (c-FLIPR)...
  31. pmc RIPK1 blocks early postnatal lethality mediated by caspase-8 and RIPK3
    Christopher P Dillon
    Department of Immunology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Cell 157:1189-202. 2014
    ..These results clarify the complex roles for RIPK1 in postnatal life and provide insights into the regulation of FADD-caspase-8 and RIPK3-MLKL signaling by RIPK1...
  32. pmc An antiapoptotic protein, c-FLIPL, directly binds to MKK7 and inhibits the JNK pathway
    Akihito Nakajima
    Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan
    EMBO J 25:5549-59. 2006
    ..However, the detailed mechanisms are unclear. Here we show that cellular FLICE-inhibitory protein (c-FLIP) is rapidly lost in NF-kappaB activation-deficient, but not wild-type fibroblasts upon TNFalpha stimulation, ..
  33. pmc A role for c-FLIP(L) in the regulation of apoptosis, autophagy, and necroptosis in T lymphocytes
    M X He
    Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA
    Cell Death Differ 20:188-97. 2013
    ..The anti-apoptotic protein c-FLIP (cellular caspase 8 (FLICE)-like inhibitory protein) suppresses death receptor-induced caspase 8 activation...
  34. doi The role of c-FLIP in cisplatin resistance of human bladder cancer cells
    Sangchul Lee
    Department of Urology, Seoul National University Bundang Hospital, Seongnam, Korea
    J Urol 189:2327-34. 2013
    ..We investigated the mechanisms underlying cisplatin resistance in human bladder cancer cells to provide novel molecular targets for the treatment of cisplatin resistant bladder cancer...
  35. doi Cellular-FLIP, Raji isoform (c-FLIP R) modulates cell death induction upon T-cell activation and infection
    Tanja Telieps
    Laboratory of Systems oriented Immunology and Inflammation Research, Institute of Molecular and Clinical Immunology, Otto von Guericke University, Magdeburg, Germany
    Eur J Immunol 43:1499-510. 2013
    ..Cellular-FLIP (c-FLIP) proteins inhibit apoptosis directly at the death-inducing signaling complex of death receptors, such as ..
  36. pmc c-FLIP maintains tissue homeostasis by preventing apoptosis and programmed necrosis
    Xuehua Piao
    Department of Immunology, Juntendo University Graduate School of Medicine, 2 1 1 Hongo, Bunkyo ku, Tokyo 113 8421, Japan
    Sci Signal 5:ra93. 2012
    As a catalytically inactive homolog of caspase-8, a proapoptotic initiator caspase, c-FLIP blocks apoptosis by binding to and inhibiting caspase-8...
  37. doi Cellular FLICE-inhibitory protein protects against cardiac remodelling after myocardial infarction
    Jinfeng Xiao
    Department of Cardiology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, 430060, People s Republic of China
    Basic Res Cardiol 107:239. 2012
    ..Thus, cFLIP gene delivery shows promise as a clinically powerful and novel therapeutic strategy for the treatment of heart failure after MI...
  38. pmc Inhibition of the intrinsic but not the extrinsic apoptosis pathway accelerates and drives MYC-driven tumorigenesis towards acute myeloid leukemia
    Kari Högstrand
    Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
    PLoS ONE 7:e31366. 2012
    ..together with anti-apoptotic proteins of relevance for AML; BCL-X(L)/BCL-2 (inhibiting the intrinsic pathway) or FLIP(L) (inhibiting the extrinsic pathway), in hematopoietic stems cells (HSCs)...
  39. pmc The role of death effector domain-containing proteins in acute oxidative cell injury in hepatocytes
    Jörn M Schattenberg
    I Department of Medicine, University Medical Center, Johannes Gutenberg University Mainz, 55101 Mainz, Germany
    Free Radic Biol Med 52:1911-7. 2012
    ..This implies that DED-containing proteins are involved in the regulation of cellular survival beyond their role in cell death receptor-ligand-mediated apoptosis...
  40. pmc Survival function of the FADD-CASPASE-8-cFLIP(L) complex
    Christopher P Dillon
    Department of Immunology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Cell Rep 1:401-7. 2012
    ....
  41. ncbi c-Flip expression and function in fetal mouse gonocytes
    Claudia Giampietri
    Istituto Pasteur Fondazione Cenci Bolognetti, Department of Histology and Medical Embryology, University of Rome La Sapienza, Rome, Italy
    FASEB J 20:124-6. 2006
    ..We evaluated the expression and function of c-Flip, an apoptosis inhibitor known to interfere with the proapoptotic Fas-signaling pathway in a variety of cell types, ..
  42. ncbi Cellular FLIP long form augments caspase activity and death of T cells through heterodimerization with and activation of caspase-8
    Austin Dohrman
    Immunobiology Program, Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405, USA
    J Immunol 175:311-8. 2005
    ..One logical candidate for this process is cellular FLIP long form (c-FLIP(L)), because it can block caspase-8 recruitment after Fas (CD95) ligation as well as directly ..
  43. pmc An essential role for c-FLIP in the efficient development of mature T lymphocytes
    Nu Zhang
    Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA
    J Exp Med 202:395-404. 2005
    ..We show that cellular FLICE-like inhibitory protein (c-FLIP), a procaspase-8-like apoptotic regulator, plays an essential role in the efficient development of mature T ..
  44. pmc KSR1 is overexpressed in endometrial carcinoma and regulates proliferation and TRAIL-induced apoptosis by modulating FLIP levels
    David Llobet
    Oncologic Pathology Group, Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova, Departament de Ciencies Mediques Basiques, Universitat de Lleida, Institut de Recerca Biomèdica de Lleida IRBLleida, Lleida, Spain
    Am J Pathol 178:1529-43. 2011
    ..Sensitization to TRAIL and agonistic anti-Fas antibody was caused by down-regulation of FLIP (FLICE-inhibitory protein)...
  45. ncbi Reduction of caspase-8 and -9 cleavage is associated with increased c-FLIP and increased binding of Apaf-1 and Hsp70 after neonatal hypoxic/ischemic injury in mice overexpressing Hsp70
    Yasuhiko Matsumori
    Department of Neurological Surgery, University of California, Department of Veterans Affairs Medical Center, San Francisco, CA 94121, USA
    Stroke 37:507-12. 2006
    ....
  46. ncbi The E3 ubiquitin ligase itch couples JNK activation to TNFalpha-induced cell death by inducing c-FLIP(L) turnover
    Lufen Chang
    Division of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute at City of Hope, City of Hope National Medical Center, 1500 E Duarte Road, KCRB 3009, Duarte, CA 91010, USA
    Cell 124:601-13. 2006
    ..we show that TNFalpha-mediated JNK activation accelerates turnover of the NF-kappaB-induced antiapoptotic protein c-FLIP, an inhibitor of caspase-8...
  47. ncbi No apparent damage in the thyroid of transgenic mice expressing antiapoptotic FLIP
    Su He Wang
    Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109 0648, USA
    Thyroid 16:1-8. 2006
    b>FLIP is an antiapoptotic protein that has been demonstrated to play an important role in inflammation, cancer, and autoimmune diseases...
  48. ncbi High resolution mapping of chromosomal regions controlling resistance to gastrointestinal nematode infections in an advanced intercross line of mice
    Jerzy M Behnke
    School of Biological Sciences, University of Nottingham, Nottingham NG7 2RD, UK
    Mamm Genome 17:584-97. 2006
    ..9-18.4 cM). Strong candidate genes for the QTL position on Chromosome 1 include genes known to be involved in regulating immune responses and on Chromosome 17 genes within the MHC, notably the Class II molecules and tumor necrosis factor...
  49. ncbi c-Flip(L) is expressed in undifferentiated mouse male germ cells
    Claudia Giampietri
    Istituto Pasteur Fondazione Cenci Bolognetti, Department of Histology and Medical Embryology, University of Rome La Sapienza, 00161 Rome, Italy
    FEBS Lett 580:6109-14. 2006
    ..Therefore pro- and anti-apoptotic proteins are essential to regulate testis physiology. c-Flip(L) is a known inhibitor of caspase 8/10 activity; in this study its perinatal expression in mouse male germ cells ..
  50. pmc Trypanosoma cruzi posttranscriptionally up-regulates and exploits cellular FLIP for inhibition of death-inducing signal
    Muneaki Hashimoto
    Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, Bunkyo ku, Tokyo 113 8421, Japan
    Mol Biol Cell 16:3521-8. 2005
    ..Here we demonstrate that the parasite dramatically up-regulates cellular FLICE inhibitory protein (c-FLIP), the only known mammalian inhibitor specific for death receptor signaling, in infected cells by an unusual, ..
  51. pmc FLIP protects against hypoxia/reoxygenation-induced endothelial cell apoptosis by inhibiting Bax activation
    Xue Wang
    Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh Medical Center, 3459 Fifth Ave, MUH NW 628, Pittsburgh, PA 15213, USA
    Mol Cell Biol 25:4742-51. 2005
    ..Using mouse lung endothelial cells (MLEC), we examined the role of FLIP, an inhibitor of caspase 8, in hypoxia/reoxygenation-induced cell death...
  52. pmc Expression of cellular FLICE inhibitory proteins (cFLIP) in normal and traumatic murine and human cerebral cortex
    Atticus H Hainsworth
    Neuroscience Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Cereb Blood Flow Metab 25:1030-40. 2005
    ..The data suggest differential spatial and temporal regulation of cFLIP-alpha and cFLIP-delta expression that may influence the magnitude of cell death and further implicate programmed mechanisms of cell death after TBI...
  53. ncbi Transgenic overexpression of the Caspase-8 inhibitor FLIP(short) leads to impaired T cell proliferation and an increased memory T cell pool after staphylococcal enterotoxin B injection
    Ina Oehme
    Georg Speyer Haus, Frankfurt, Germany
    Eur J Immunol 35:1240-9. 2005
    The cellular homologues of the viral anti-apoptotic v-FLIP proteins exist as a long (c-FLIP(L)) and a short (c-FLIP(S)) splice variant...
  54. pmc Keratins modulate c-Flip/extracellular signal-regulated kinase 1 and 2 antiapoptotic signaling in simple epithelial cells
    Stéphane Gilbert
    Centre de Recherche en Cancérologie et Département de médecine, Universite Laval, and Centre de Recherche de L Hôtel Dieu de Québec, Quebec G1R 2J6, Canada
    Mol Cell Biol 24:7072-81. 2004
    ..In turn, this impaired ERK1/2 activation in K8-null hepatocytes is associated with a drastic reduction in c-Flip protein, an event that also holds in a K8-null mouse mammary cell line...
  55. ncbi The Akt-regulated forkhead transcription factor FOXO3a controls endothelial cell viability through modulation of the caspase-8 inhibitor FLIP
    Carsten Skurk
    Molecular Cardiology Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    J Biol Chem 279:1513-25. 2004
    FLICE-inhibitory protein (FLIP) is a homolog of caspase-8 that lacks catalytic activity and has been shown to be important in protecting endothelial cells from apoptosis...
  56. pmc Differential sensitivity of endothelial cells of various species to apoptosis induced by gene transfer of Fas ligand: role of FLIP levels
    Delphine Bouchet
    Institut National de la Sante et de la Recherche Medicale U437, Nantes, France
    Mol Med 8:612-23. 2002
    ..In human ECs, levels of FLICE/caspase 8-inhibitory protein (FLIP) have been shown to control apoptosis mediated by Fas.
  57. ncbi Lymphoadenopathy in IL-2-deficient mice: further characterization and overexpression of the antiapoptotic molecule cellular FLIP
    Patricia Chastagner
    Unité d Immunogénétique Cellulaire, Département de Médecine Moléculaire, Institut Pasteur, Paris, France
    J Immunol 169:3644-51. 2002
    ..Because the apoptosis inhibitor FLIP has been shown in vitro to participate in the IL-2 control of activation-induced cell death, we analyze its ..
  58. ncbi Nuclear factor kappaB-mediated induction of Flice-like inhibitory protein prevents tumor necrosis factor alpha-induced apoptosis in rat granulosa cells
    Chao Wu Xiao
    Reproductive Biology Unit and Division of Reproductive Medicine, University of Ottawa, Ottawa Health Research Institute, The Ottawa Hospital Civic Campus, 725 Parkdale Avenue, Ottawa, Ontario, Canada K1Y 4E9
    Biol Reprod 67:436-41. 2002
    ..of the present studies was to examine the role and regulation of the antiapoptotic Flice-like inhibitory protein (FLIP) in rat granulosa cells by tumor necrosis factor alpha (TNFalpha) in vitro...
  59. ncbi Regulation of Fas ligand-induced apoptosis by TNF
    B D Elzey
    Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 167:3049-56. 2001
    ..In vitro, TNF enhanced the Fas-mediated apoptosis of unactivated T cells through decreased intracellular levels of FLIP and increased production of the pro-apoptotic molecule Bax. This effect was mediated through the TNFR2 receptor...
  60. ncbi NOD Idd5 locus controls insulitis and diabetes and overlaps the orthologous CTLA4/IDDM12 and NRAMP1 loci in humans
    N J Hill
    Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge University, UK
    Diabetes 49:1744-7. 2000
    ..4-cM interval. Idd5.1 is in the proximal 1.5-cM portion of the interval and contains the candidates Casp8, Cflar (FLIP), Cd28, and Cd152 (CTLA4). Idd5.1 overlaps the orthologous CTLA4/IDDM12 locus in humans. Idd5...
  61. ncbi Inhibition of Fas-mediated apoptosis by the B cell antigen receptor through c-FLIP
    J Wang
    Laboratory of Immunology National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA
    Eur J Immunol 30:155-63. 2000
    ..death-inducing signaling complex (DISC), including Fas, FADD, caspase-8 and cellular FLICE-inhibitory protein (c-FLIP). No significant changes in the cellular levels of Fas, FADD or caspase-8 were observed after BCR cross-linking...
  62. pmc A role for cFLIP in B cell proliferation and stress MAPK regulation
    Haibing Zhang
    Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
    J Immunol 182:207-15. 2009
    ..Cellular FLIP (cFLIP) is a homolog of caspase 8 and is also capable of binding to FADD...
  63. ncbi FLIP inhibits endothelial cell apoptosis during hyperoxia by suppressing Bax
    Xue Wang
    Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh Medical Center, 3459 Fifth Avenue, MUH 628NW, Pittsburgh, PA 15213, USA
    Free Radic Biol Med 42:1599-609. 2007
    ..We examined the hypothesis that FLIP, an inhibitor of caspase-8, can protect endothelial cells against the lethal effects of hyperoxia...
  64. pmc Caspase-8 and c-FLIPL associate in lipid rafts with NF-kappaB adaptors during T cell activation
    Ravi S Misra
    Immunobiology Program, Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont 05405 0068, USA
    J Biol Chem 282:19365-74. 2007
    ..We observe that following TCR ligation, a small portion of total cellular caspase-8 and c-FLIP(L) rapidly migrate to lipid rafts where they associate in an active caspase complex...
  65. ncbi Met signals hepatocyte survival by preventing Fas-triggered FLIP degradation in a PI3k-Akt-dependent manner
    Anice Moumen
    Developmental Biology Institute of Marseille Luminy IBDML UMR 6216, CNRS Univ de la Mediterranée, Marseille, France
    Hepatology 45:1210-7. 2007
    ..of caspase-8 activation and cell death is a protective mechanism modulated by the FLICE-Like Inhibitory Protein (FLIP)...
  66. ncbi Genetic analysis of hyperoxic acute lung injury survival in reciprocal intercross mice
    Daniel R Prows
    Department of Pediatrics, University of Cincinnati College of Medicine, Children s Hospital Medical Center, Cincinnati, Ohio, USA
    Physiol Genomics 30:271-81. 2007
    ..QTL results confirmed that both parental strains contribute dominant resistance alleles to their offspring to determine individual HALI susceptibility...
  67. ncbi FLIP(L) protects neurons against in vivo ischemia and in vitro glucose deprivation-induced cell death
    Era Taoufik
    Laboratory of Molecular Genetics, Hellenic Pasteur Institute, 11521 Athens, Greece
    J Neurosci 27:6633-46. 2007
    ..long isoform of cellular Fas-associated death domain-like interleukin-1-beta-converting enzyme-inhibitory protein (FLIP(L))...
  68. ncbi Expression of transgenic FLIP on thyroid epithelial cells inhibits induction and promotes resolution of granulomatous experimental autoimmune thyroiditis in CBA/J mice
    Yujiang Fang
    Division of Immunology and Rheumatology, Department of Medicine, University of Missouri, NE307 Medical Sciences, Columbia, MO 65212, USA
    Endocrinology 148:5734-45. 2007
    ..We showed that expression of Fas-associated death domain-like IL-1beta-converting enzyme inhibitory protein (FLIP) transgene (Tg) on thyroid epithelial cells (TECs) of DBA/1 mice had no effect on G-EAT induction but promoted ..
  69. ncbi Cellular FLIP long isoform transgenic mice overcome inherent Th2-biased immune responses to efficiently resolve Leishmania major infection
    Vivian Tseveleki
    Laboratory of Molecular Genetics, Hellenic Pasteur Institute, 127 Vasilissis Sophias Avenue, 115 21 Athens, Greece
    Int Immunol 19:1183-9. 2007
    c-FLIP(L) expression in T cells is required for mounting effective T cell responses and can also be critical for effector T cell differentiation, as has recently been shown by a number of in vivo studies in conditional knockout and ..
  70. ncbi C/EBPbeta associates with caspase 8 complex proteins and modulates apoptosis in hepatic stellate cells
    Martina Buck
    Department of Medicine and Cancer Center, Veterans Healthcare Medical Center and University of California, San Diego, CA 92161, USA
    J Clin Gastroenterol 41:S295-9. 2007
    ..To analyze the role of C/EBPbeta phosphorylation on hepatic stellate cell survival/cell death...
  71. pmc c-FLIP(S) reduces activation of caspase and NF-kappaB pathways and decreases T cell survival
    Jennifer Hinshaw-Makepeace
    Immunobiology Program, Department of Medicine, The University of Vermont College of Medicine, Burlington, VT 05405 0068, USA
    Eur J Immunol 38:54-63. 2008
    ..A likely candidate is cellular FLIP (c-FLIP), an enzymatically inert caspase-8 homologue...
  72. doi Mutational analyses of c-FLIPR, the only murine short FLIP isoform, reveal requirements for DISC recruitment
    N Ueffing
    Institute of Molecular Medicine, University of Dusseldorf, Universitatsstrasse 1, Dusseldorf D 40225, Germany
    Cell Death Differ 15:773-82. 2008
    Cellular FLICE-inhibitory protein (c-FLIP) proteins are known as potent inhibitors of death receptor-mediated apoptosis by interfering with caspase-8 activation at the death-inducing signaling complex (DISC)...
  73. pmc Cultured murine thyroid epithelial cells expressing transgenic Fas-associated death domain-like interleukin-1beta converting enzyme inhibitory protein are protected from fas-mediated apoptosis
    Yujiang Fang
    Division of Immunology and Rheumatology, Department of Medicine, University of Missouri, NE307 Medical Sciences, Columbia, MO 65212, USA
    Endocrinology 149:3321-9. 2008
    The antiapoptotic molecule Fas-associated death domain-like IL-1beta-converting enzyme inhibitory protein (FLIP) inhibits Fas-mediated apoptosis by blocking activation of caspase-8...
  74. ncbi The long isoform of cellular FLIP is essential for T lymphocyte proliferation through an NF-kappaB-independent pathway
    Nu Zhang
    Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA
    J Immunol 180:5506-11. 2008
    Although the long isoform of cellular FLIP (c-FLIP(L)) has been implicated in TCR-mediated signaling, its role in T cell proliferation remains controversial...
  75. doi Cyclic AMP inhibits JNK activation by CREB-mediated induction of c-FLIP(L) and MKP-1, thereby antagonizing UV-induced apoptosis
    J Zhang
    Department of Molecular Immunology, Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, PR China
    Cell Death Differ 15:1654-62. 2008
    ..The induction of the long form of cellular FLICE-inhibitory protein (c-FLIP(L)) and mitogen-activated protein kinase phosphatase-1 (MKP-1), but not DLC and p21(WAF1) by CREB was required for ..
  76. pmc c-FLIP protects mature T lymphocytes from TCR-mediated killing
    Nu Zhang
    Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA
    J Immunol 181:5368-73. 2008
    Although c-FLIP has been identified as an important player in the extrinsic (death receptor-induced) apoptosis pathway, its endogenous function in mature T lymphocytes remains undefined...
  77. ncbi Intrinsic resistance to TNF-alpha-induced hepatocyte apoptosis in ICR mice correlates with expression of a short form of c-FLIP
    Shinji Takai
    Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan
    Lab Invest 87:572-81. 2007
    ..Interestingly, the short form of cellular FLICE/caspase-8-inhibitory protein (c-FLIP(S)) was constitutively upregulated in ICR mice...
  78. ncbi Selective inhibition of IkappaB kinase sensitizes mantle cell lymphoma B cells to TRAIL by decreasing cellular FLIP level
    Gaël Roué
    Hematopathology Unit, Hospital Clinic, Institut d Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Barcelona, Spain
    J Immunol 178:1923-30. 2007
    ..TRAIL was closely linked to the activity of the NF-kappaB p50 factor and to the consequent expression of cellular FLIP (c-FLIP), which accumulated into the TRAIL-dependent complex in resistant cells...
  79. doi Genetic deletion of faim reveals its role in modulating c-FLIP expression during CD95-mediated apoptosis of lymphocytes and hepatocytes
    J Huo
    Laboratory of Immunology, Bioprocessing Technology Institute, Agency for Science, Technology and Research A STAR, Singapore
    Cell Death Differ 16:1062-70. 2009
    ..Detailed biochemical analyses further reveal the decreased expression of c-FLIP(L) and c-FLIP(R) in faim(-/-) thymocytes and increased association of caspase-8 with Fas in Fas-activated mutant ..
  80. doi CAGE, a cancer/testis antigen, induces c-FLIP(L) and Snail to enhance cell motility and increase resistance to an anti-cancer drug
    Youngmi Kim
    School of Biological Sciences, College of Natural Sciences, Kangwon National University, Chunchon, 200 701, Republic of Korea
    Biotechnol Lett 31:945-52. 2009
    ..CAGE was shown to protect cells against celastrol, an anti-cancer agent. Celastrol-resistant B16F10 melanoma cells had a higher expression level of c-FLIP(L) and Snail as compared with a sensitive cell line.
  81. doi Rocaglamide sensitizes leukemic T cells to activation-induced cell death by differential regulation of CD95L and c-FLIP expression
    J Y Zhu
    Tumorimmunology Program D030, German Cancer Research Center, D 69120 Heidelberg, Germany
    Cell Death Differ 16:1289-99. 2009
    ..preferentially promotes activation-induced cell death in malignant T cells by differential regulation of c-FLIP and CD95L expression...
  82. pmc Abundant c-Fas-associated death domain-like interleukin-1-converting enzyme inhibitory protein expression determines resistance of T helper 17 cells to activation-induced cell death
    Yu Yu
    Departments of Immunology and Blood and Marrow Transplantation, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612 9497, USA
    Blood 114:1026-8. 2009
    ..The resistance of Th17 cells to AICD reveals a novel mechanism to explain the high pathogenicity of Th17 cells in autoimmune diseases, and may also provide a rationale to generate tumor-specific Th17 cells for adoptive immunotherapy...
  83. pmc GLUT1-induced cFLIP expression promotes proliferation and prevents apoptosis in vascular smooth muscle cells
    Eileen D Vesely
    Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Am J Physiol Cell Physiol 297:C759-65. 2009
    ..Taken together, these data suggest that GLUT1 induction of cFLIP(L) expression augments proliferation and prevents apoptosis in VSMCs...
  84. pmc FasL gene-deficient mice display a limited disruption in spermatogenesis and inhibition of mono-(2-ethylhexyl) phthalate-induced germ cell apoptosis
    Yi Chen Lin
    Division of Pharmacology and Toxicology, Center for Molecular and Cellular Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712 1074, USA
    Toxicol Sci 114:335-45. 2010
    ..cell toxicant, unexpectedly caused a rapid decrease in the germ cell AI that paralleled increased levels of the CFLAR (c-FLIP) protein, a known inhibitor of death receptor signaling...
  85. doi Expression of cellular FLIP by B cells is required for their participation in an immune response
    Francis Coffey
    Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USA
    J Immunol 184:4871-9. 2010
    High levels of the Fas-signaling antagonist cellular FLIP (cFLIP) in germinal center (GC) B cells suggests an important role for this factor during this stage of the T cell-dependent B cell immune response...
  86. pmc FLIP: a novel regulator of macrophage differentiation and granulocyte homeostasis
    Qi Quan Huang
    Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
    Blood 116:4968-77. 2010
    b>FLIP is a well-established suppressor of death receptor-mediated apoptosis. To define its essential in vivo role in myeloid cells, we generated and characterized mice with Flip conditionally deleted in the myeloid lineage...
  87. pmc Toll-like receptor 9-mediated inhibition of apoptosis occurs through suppression of FoxO3a activity and induction of FLIP expression
    Eun Jung Lim
    Aging Associated Vascular Disease Research Center, Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu 705 802, Korea
    Exp Mol Med 42:712-20. 2010
    ..prevented apoptosis induced by serum deprivation through increased expression of FLICE-like inhibitory protein (FLIP). CpG ODN-mediated anti-apoptosis depended on the TLR9-Akt-FoxO3a signaling pathway...
  88. pmc Regulation of steady-state neutrophil homeostasis by macrophages
    Claire Gordy
    Department of Immunology, Duke University Medical Center, Durham, NC, USA
    Blood 117:618-29. 2011
    ..By conditionally deleting the antiapoptotic gene cellular FLICE-like inhibitory protein (C-FLIP) in myeloid cells, we have generated a novel mouse model deficient in marginal zone and bone marrow stromal ..
  89. pmc c-Flip overexpression affects satellite cell proliferation and promotes skeletal muscle aging
    C Giampietri
    Istituto Pasteur Fondazione Cenci Bolognetti, Department of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy
    Cell Death Dis 1:e38. 2010
    This study shows that forcing c-Flip overexpression in undifferentiated skeletal myogenic cells in vivo results in early aging muscle phenotype...