title: Regulation of CD95/Fas signaling at the DISC.
abstract: CD95 (APO-1/Fas) is a member of the death receptor (DR) family. Stimulation of CD95 leads to induction of apoptotic and non-apoptotic signaling pathways. The formation of the CD95 death-inducing signaling complex (DISC) is the initial step of CD95 signaling. Activation of procaspase-8 at the DISC leads to the induction of DR-mediated apoptosis. The activation of procaspase-8 is blocked by cellular FLICE-inhibitory proteins (c-FLIP). This review is focused on the role in the CD95-mediated signaling of the death effector domain-containing proteins procaspase-8 and c-FLIP. We discuss how dynamic cross-talk between procaspase-8 and c-FLIP at the DISC regulates life/death decisions at CD95.
authors.affiliation: Division of Immunogenetics, Tumorimmunology Program German Cancer Research Center, Heidelberg, Germany.
authors.forename: I N
authors.initials: IN
authors.lastname: Lavrik
authors.forename: P H
authors.initials: PH
authors.lastname: Krammer
mesh_terms: D017209:Apoptosis; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000378:metabolism*; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D006801:Humans; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D053418:Death Domain Receptor Signaling Adaptor Proteins; C491901:FAS protein, human; D053200:Fas-Associated Death Domain Protein; D019014:fas Receptor; D053181:Caspase 8; D053453:Caspase 9
references.citation: EMBO J. 2006 May 3;25(9):1895-905
references.pmid: 16619028
references.citation: Curr Opin Immunol. 1998 Oct;10(5):552-8
references.pmid: 9794838
references.citation: Nature. 2009 Oct 1;461(7264):659-63
references.pmid: 19794494
references.citation: Nature. 1999 Aug 26;400(6747):886-91
references.pmid: 10476969
references.citation: EMBO J. 1997 May 15;16(10):2794-804
references.pmid: 9184224
references.citation: Cell. 2007 May 4;129(3):447-50
references.pmid: 17482535
references.citation: J Biol Chem. 1999 Jan 15;274(3):1541-8
references.pmid: 9880531
references.citation: Nature. 2009 Aug 20;460(7258):1035-9
references.pmid: 19626005
references.citation: Nature. 2000 Oct 12;407(6805):789-95
references.pmid: 11048730
references.citation: Nat Rev Immunol. 2006 Mar;6(3):196-204
references.pmid: 16498450
references.citation: Cell. 1993 Dec 17;75(6):1169-78
references.pmid: 7505205
references.citation: Nat Med. 2004 Apr;10(4):389-95
references.pmid: 15004554
references.citation: J Biol Chem. 2002 Nov 22;277(47):45162-71
references.pmid: 12215447
references.citation: Mol Cell Biol. 2001 Dec;21(24):8247-54
references.pmid: 11713262
references.citation: J Biol Chem. 2005 Apr 15;280(15):14507-13
references.pmid: 15701649
references.citation: J Biol Chem. 2007 May 4;282(18):13664-71
references.pmid: 17347143
references.citation: J Cell Biol. 2004 Sep 13;166(6):839-51
references.pmid: 15364960
references.citation: J Biol Chem. 2001 Jun 8;276(23):20633-40
references.pmid: 11279218
references.citation: Nature. 1997 Apr 3;386(6624):517-21
references.pmid: 9087414
references.citation: Cell. 2007 Apr 20;129(2):423-33
references.pmid: 17448999
references.citation: Curr Opin Biotechnol. 2010 Aug;21(4):551-5
references.pmid: 20674332
references.citation: Nat Struct Mol Biol. 2010 Nov;17(11):1324-9
references.pmid: 20935634
references.citation: Cancer Cell. 2008 Mar;13(3):235-48
references.pmid: 18328427
references.citation: Cell Death Differ. 2006 Jan;13(1):31-40
references.pmid: 16003386
references.citation: Mol Cell Biol. 2004 Apr;24(7):2627-36
references.pmid: 15024054
references.citation: J Immunol. 2005 May 1;174(9):5270-8
references.pmid: 15843523
references.citation: J Immunol. 2008 Aug 15;181(4):2522-32
references.pmid: 18684943
references.citation: J Cell Biol. 2009 Dec 28;187(7):1037-54
references.pmid: 20038679
references.citation: J Biol Chem. 2008 Sep 26;283(39):26401-8
references.pmid: 18635548
references.citation: Science. 2000 Jun 30;288(5475):2354-7
references.pmid: 10875918
references.citation: Nature. 2011 Mar 17;471(7338):368-72
references.pmid: 21368762
references.citation: J Biol Chem. 1997 Oct 24;272(43):26953-8
references.pmid: 9341131
references.citation: Mol Cell. 2009 Aug 14;35(3):265-79
references.pmid: 19683492
references.citation: EMBO J. 2002 Sep 2;21(17):4520-30
references.pmid: 12198154
references.citation: Mol Biosyst. 2009 Oct;5(10):1105-11
references.pmid: 19756299
references.citation: Biochemistry. 2007 Apr 10;46(14):4398-407
references.pmid: 17371051
references.citation: Cell. 2003 Jul 25;114(2):181-90
references.pmid: 12887920
references.citation: Cell. 2009 May 15;137(4):721-35
references.pmid: 19427028
references.citation: EMBO J. 1998 Mar 16;17(6):1675-87
references.pmid: 9501089
references.citation: Mol Syst Biol. 2010;6:352
references.pmid: 20212524
references.citation: Mol Cell Biol. 2009 Aug;29(16):4431-40
references.pmid: 19528225
references.citation: Immunity. 1998 Aug;9(2):267-76
references.pmid: 9729047
references.citation: J Cell Biol. 2010 Aug 9;190(3):377-89
references.pmid: 20696707
references.citation: Nature. 1997 Jul 10;388(6638):190-5
references.pmid: 9217161
references.citation: J Exp Med. 2006 May 15;203(5):1295-305
references.pmid: 16682493
references.citation: Cell Death Differ. 2003 Jan;10(1):144-5
references.pmid: 12655304
references.citation: EMBO J. 2003 Aug 15;22(16):4132-42
references.pmid: 12912912
references.citation: Cell. 1993 Sep 10;74(5):845-53
references.pmid: 8397073
references.citation: Nat Rev Immunol. 2007 Jul;7(7):532-42
references.pmid: 17589543
references.citation: Science. 2005 Mar 4;307(5714):1465-8
references.pmid: 15746428
references.citation: J Clin Invest. 2005 Oct;115(10):2665-72
references.pmid: 16200200
references.citation: Cell Death Differ. 2006 Mar;13(3):489-98
references.pmid: 16179941
references.citation: J Biol Chem. 2005 Dec 9;280(49):40599-608
references.pmid: 16227629
references.citation: Curr Biol. 2000 Jun 1;10(11):640-8
references.pmid: 10837247
references.citation: Cell. 1996 Jun 14;85(6):817-27
references.pmid: 8681377
references.citation: J Biol Chem. 1998 Jan 30;273(5):2926-30
references.pmid: 9446604
references.citation: Science. 1989 Jul 21;245(4915):301-5
references.pmid: 2787530
references.citation: Trends Biochem Sci. 2001 Aug;26(8):475-81
references.pmid: 11504623
references.citation: Nature. 2009 Feb 19;457(7232):1019-22
references.pmid: 19118384
references.citation: Nat Cell Biol. 2003 Feb;5(2):118-25
references.pmid: 12545171
references.citation: Mol Cell Biol. 2010 Dec;30(24):5726-40
references.pmid: 20937773