Model-based dissection of CD95 signaling dynamics reveals both a pro- and antiapoptotic role of c-FLIPL

Journal of Cell Biology

Volumn 190, Issue 3, 2010, Pages 377-389

  Fricker, Nicolai ^a,b   Beaudouin, Joel ^a,b   Richter, Petra ^a,b   Eils, Roland ^a,b   Krammer, Peter H ^a   Lavrik, Inna N ^a,b  

^a GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^b UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CASPASE 8; DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEIN; FAS ANTIGEN; FLICE INHIBITORY PROTEIN;

APOPTOSIS; ARTICLE; CONTROLLED STUDY; ENZYME ACTIVATION; HELA CELL; MATHEMATICAL MODEL; MOLECULAR IMAGING; PRIORITY JOURNAL; SENSITIZATION; SIGNAL TRANSDUCTION; STOICHIOMETRY; WILD TYPE;

ALGORITHMS; ANTIGENS, CD95; APOPTOSIS; BLOTTING, WESTERN; CASP8 AND FADD-LIKE APOPTOSIS REGULATING PROTEIN; CASPASE 8; COMPUTER SIMULATION; HELA CELLS; HUMANS; MODELS, BIOLOGICAL; PROTEIN ISOFORMS; SIGNAL TRANSDUCTION;

EID: 77955465116     PISSN: 00219525     EISSN: 00219525     Source Type: Journal    
DOI: 10.1083/jcb.201002060     Document Type: Article

References (45)

1. Albeck, J.G., J.M. Burke, B.B. Aldridge, M. Zhang, D.A. Lauffenburger, and P.K. Sorger. 2008a. Quantitative analysis of pathways controlling extrinsic apoptosis in single cells. Mol. Cell. 30:11-25. doi:10.1016/j.molcel.2008.02.012
2. Albeck, J.G., J.M. Burke, S.L. Spencer, D.A. Lauffenburger, and P.K. Sorger. 2008b. Modeling a snap-action, variable-delay switch controlling extrinsic cell death. PLoS Biol. 6:2831-2852. doi:10.1371/journal.pbio.0060299
3. Bentele, M., I. Lavrik, M. Ulrich, S. Stösser, D.W. Heermann, H. Kalthoff, P.H. Krammer, and R. Eils. 2004. Mathematical modeling reveals threshold mechanism in CD95-induced apoptosis. J. Cell Biol. 166:839-851. doi:10.1083/jcb.200404158
4. Budd, R.C., W.C. Yeh, and J. Tschopp. 2006. cFLIP regulation of lymphocyte activation and development. Nat. Rev. Immunol. 6:196-204. doi:10.1038/nri1787
5. Chang, D.W., Z. Xing, Y. Pan, A. Algeciras-Schimnich, B.C. Barnhart, S. Yaish-Ohad, M.E. Peter, and X. Yang. 2002. c-FLIP(L) is a dual function regulator for caspase-8 activation and CD95-mediated apoptosis. EMBO J. 21:3704-3714. doi:10.1093/emboj/cdf356
6. Chang, D.W., Z. Xing, V.L. Capacio, M.E. Peter, and X. Yang. 2003. Interdimer processing mechanism of procaspase-8 activation. EMBO J. 22:4132-4142. doi:10.1093/emboj/cdg414
7. Dohrman, A., T. Kataoka, S. Cuenin, J.Q. Russell, J. Tschopp, and R.C. Budd. 2005. Cellular FLIP (long form) regulates CD8+ T cell activation through caspase-8-dependent NF-kappa B activation. J. Immunol. 174:5270-5278. (Pubitemid 40593165)
8. Eissing, T., H. Conzelmann, E.D. Gilles, F. Allgöwer, E. Bullinger, and P. Scheurich. 2004. Bistability analyses of a caspase activation model for receptor-induced apoptosis. J. Biol. Chem. 279:36892-36897. doi:10.1074/jbc. M404893200
9. Fuentes-Prior, P., and G.S. Salvesen. 2004. The protein structures that shape caspase activity, specificity, activation and inhibition. Biochem. J. 384:201-232. doi:10.1042/BJ20041142
10. Golks, A., D. Brenner, C. Fritsch, P.H. Krammer, and I.N. Lavrik. 2005. c-FLIPR, a new regulator of death receptor-induced apoptosis. J. Biol. Chem. 280:14507-14513. doi:10.1074/jbc.M414425200
11. Golks, A., D. Brenner, P.H. Krammer, and I.N. Lavrik. 2006. The c-FLIPNH2 terminus (p22-FLIP) induces NF-kappaB activation. J. Exp. Med. 203:1295-1305. doi:10.1084/jem.20051556
12. Hoffmann, J.C., A. Pappa, P.H. Krammer, and I.N. Lavrik. 2009. A new C-terminal cleavage product of procaspase-8, p30, defines an alternative pathway of procaspase-8 activation. Mol. Cell. Biol. 29:4431-4440. doi:10.1128/MCB. 02261-07
13. Hughes, M.A., N. Harper, M. Butterworth, K. Cain, G.M. Cohen, and M. MacFarlane. 2009. Reconstitution of the death-inducing signaling complex reveals a substrate switch that determines CD95-mediated death or survival. Mol. Cell. 35:265-279. doi:10.1016/j.molcel.2009.06.012
14. Kang, T.B., G.S. Oh, E. Scandella, B. Bolinger, B. Ludewig, A. Kovalenko, and D. Wallach. 2008. Mutation of a self-processing site in caspase-8 compromises its apoptotic but not its nonapoptotic functions in bacterial artificial chromosome-transgenic mice. J. Immunol. 181:2522-2532.
15. Kataoka, T., and J. Tschopp. 2004. N-terminal fragment of c-FLIP(L) processed by caspase 8 specifically interacts with TRAF2 and induces activation of the NF-kappaB signaling pathway. Mol. Cell. Biol. 24:2627-2636. doi:10.1128/MCB.24.7.2627-2636.2004 (Pubitemid 38381257)
16. Kataoka, T., R.C. Budd, N. Holler, M. Thome, F. Martinon, M. Irmler, K. Burns, M. Hahne, N. Kennedy, M. Kovacsovics, and J. Tschopp. 2000. The caspase-8 inhibitor FLIP promotes activation of NF-kappaB and Erk signaling pathways. Curr. Biol. 10:640-648. doi:10.1016/S0960-9822(00)00512-1
17. Kaunisto, A., V. Kochin, T. Asaoka, A. Mikhailov, M. Poukkula, A. Meinander, and J.E. Eriksson. 2009. PKC-mediated phosphorylation regulates c-FLIP ubiquitylation and stability. Cell Death Differ. 16:1215-1226. doi:10.1038/cdd.2009.35
18. Kischkel, F.C., S. Hellbardt, I. Behrmann, M. Germer, M. Pawlita, P.H. Krammer, and M.E. Peter. 1995. Cytotoxicity-dependent APO-1 (Fas/CD95)- associated proteins form a death-inducing signaling complex (DISC) with the receptor. EMBO J. 14:5579-5588.
19. Krammer, P.H., R. Arnold, and I.N. Lavrik. 2007. Life and death in peripheral T cells. Nat. Rev. Immunol. 7:532-542. doi:10.1038/nri2115
20. Krueger, A., I. Schmitz, S. Baumann, P.H. Krammer, and S. Kirchhoff. 2001. Cellular FLICE-inhibitory protein splice variants inhibit different steps of caspase-8 activation at the CD95 death-inducing signaling complex. J. Biol. Chem. 276:20633-20640. doi:10.1074/jbc.M101780200 (Pubitemid 33651791)
21. Lavrik, I.N., A. Golks, and P.H. Krammer. 2005a. Death receptor signaling. J. Cell Sci. 118:265-267. doi:10.1242/jcs.01610
22. Lavrik, I.N., A. Golks, and P.H. Krammer. 2005b. Caspases: pharmacological manipulation of cell death. J. Clin. Invest. 115:2665-2672. doi:10.1172/JCI26252
23. Lavrik, I.N., A. Golks, D. Riess, M. Bentele, R. Eils, and P.H. Krammer. 2007. Analysis of CD95 threshold signaling: triggering of CD95 (FAS/APO-1) at low concentrations primarily results in survival signaling. J. Biol. Chem. 282:13664-13671. doi:10.1074/jbc.M700434200
24. Lavrik, I.N., R. Eils, N. Fricker, C. Pforr, and P.H. Krammer. 2009. Understanding apoptosis by systems biology approaches. Mol. Biosyst. 5:1105-1111. doi:10.1039/b905129p
25. Legewie, S., N. Blüthgen, and H. Herzel. 2006. Mathematical modeling identifies inhibitors of apoptosis as mediators of positive feedback and bistability. PLOS Comput. Biol. 2:e120. doi:10.1371/journal.pcbi.0020120
26. Medema, J.P., C. Scaffidi, F.C. Kischkel, A. Shevchenko, M. Mann, P.H. Krammer, and M.E. Peter. 1997. FLICE is activated by association with the CD95 death-inducing signaling complex (DISC). EMBO J. 16:2794-2804. doi:10.1093/emboj/16.10.2794
27. Micheau, O., M. Thome, P. Schneider, N. Holler, J. Tschopp, D.W. Nicholson, C. Briand, and M.G. Grütter. 2002. The long form of FLIP is an activator of caspase-8 at the Fas death-inducing signaling complex. J. Biol. Chem. 277:45162-45171. doi:10.1074/jbc.M206882200
28. Muzio, M., A.M. Chinnaiyan, F.C. Kischkel, K. O'Rourke, A. Shevchenko, J. Ni, C. Scaffidi, J.D. Bretz, M. Zhang, R. Gentz, et al. 1996. FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex. Cell. 85:817-827. doi:10.1016/S0092-8674(00) 81266-0 (Pubitemid 26193033)
29. Muzio, M., B.R. Stockwell, H.R. Stennicke, G.S. Salvesen, and V.M. Dixit. 1998. An induced proximity model for caspase-8 activation. J. Biol. Chem. 273:2926-2930. doi:10.1074/jbc.273.5.2926
30. Neumann, L., C. Pforr, J. Beaudouin, A. Pappa, N. Fricker, P.H. Krammer, I.N. Lavrik, and R. Eils. 2010. Dynamics within the CD95 death-inducing signaling complex decide life and death of cells. Mol. Syst. Biol. 6:352. doi:10.1038/msb.2010.6
31. Peter, M.E., R.C. Budd, J. Desbarats, S.M. Hedrick, A.O. Hueber, M.K. Newell, L.B. Owen, R.M. Pope, J. Tschopp, H. Wajant, et al. 2007. The CD95 receptor: apoptosis revisited. Cell. 129:447-450. doi:10.1016/j.cell.2007.04.031
32. Rehm, M., H.J. Huber, H. Dussmann, and J.H. Prehn. 2006. Systems analysis of effector caspase activation and its control by X-linked inhibitor of apoptosis protein. EMBO J. 25:4338-4349. doi:10.1038/sj.emboj.7601295
33. Rehm, M., H.J. Huber, C.T. Hellwig, S. Anguissola, H. Dussmann, and J.H. Prehn. 2009. Dynamics of outer mitochondrial membrane permeabilization during apoptosis. Cell Death Differ. 16:613-623. doi:10.1038/cdd.2008.187
34. Scaffidi, C., J.P. Medema, P.H. Krammer, and M.E. Peter. 1997. FLICE is predominantly expressed as two functionally active isoforms, caspase-8/a and caspase-8/b. J. Biol. Chem. 272:26953-26958. doi:10.1074/jbc.272.43.26953 (Pubitemid 27452647)
35. Scaffidi, C., I. Schmitz, P.H. Krammer, and M.E. Peter. 1999. The role of c-FLIP in modulation of CD95-induced apoptosis. J. Biol. Chem. 274:1541-1548. doi:10.1074/jbc.274.3.1541
36. Schmidt, H., and M. Jirstrand. 2006. Systems biology toolbox for MATLAB: a computational platform for research in systems biology. Bioinformatics. 22:514-515. doi:10.1093/bioinformatics/bti799
37. Sharp, D.A., D.A. Lawrence, and A. Ashkenazi. 2005. Selective knockdown of the long variant of cellular FLICE inhibitory protein augments death receptor-mediated caspase-8 activation and apoptosis. J. Biol. Chem. 280:19401-19409. doi:10.1074/jbc.M413962200
38. Spencer, S.L., S. Gaudet, J.G. Albeck, J.M. Burke, and P.K. Sorger. 2009. Nongenetic origins of cell-to-cell variability in TRAIL-induced apoptosis. Nature. 459:428-432. doi:10.1038/nature08012
39. Sprick, M.R., E. Rieser, H. Stahl, A. Grosse-Wilde, M.A. Weigand, and H. Walczak. 2002. Caspase-10 is recruited to and activated at the native TRAIL and CD95 death-inducing signalling complexes in a FADD-dependent manner but can not functionally substitute caspase-8. EMBO J. 21:4520-4530. doi:10.1093/emboj/ cdf441
40. Suda, T., T. Takahashi, P. Golstein, and S. Nagata. 1993. Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Cell. 75:1169-1178. doi:10.1016/0092-8674(93)90326-L
41. Trauth, B.C., C. Klas, A.M. Peters, S. Matzku, P. Möller, W. Falk, K.M. Debatin, and P.H. Krammer. 1989. Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science. 245:301-305. doi:10.1126/science. 2787530
42. Ueffing, N., E. Keil, C. Freund, R. Kühne, K. Schulze-Osthoff, and I. Schmitz. 2008. Mutational analyses of c-FLIPR, the only murine short FLIP isoform, reveal requirements for DISC recruitment. Cell Death Differ. 15:773-782. doi:10.1038/sj.cdd.4402314 (Pubitemid 351405082)
43. Walczak, H., R.E. Miller, K. Ariail, B. Gliniak, T.S. Griffith, M. Kubin, W. Chin, J. Jones, A. Woodward, T. Le, et al. 1999. Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nat. Med. 5:157-163. doi:10.1038/5517 (Pubitemid 29068521)
44. Yu, J.W., and Y. Shi. 2008. FLIP and the death effector domain family. Oncogene. 27:6216-6227. doi:10.1038/onc.2008.299
45. Yu, J.W., P.D. Jeffrey, and Y. Shi. 2009. Mechanism of procaspase-8 activation by c-FLIPL. Proc. Natl. Acad. Sci. USA. 106:8169-8174. doi:10.1073/pnas.0812453106