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Alternative Fas-mediated cell death pathway is dependent on the different cleavage patterns of procaspase-8

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Abstract

It has been reported that mitochondria-independent or mitochondria-dependent (type I/II) Fas signaling pathways in leukemia cells depend on the amount of active caspase-8. However, Bid molecules, which could not be cleaved in type I cells, could be effectively cleaved by recombinant active caspase-8 in vitro. The cleavage of recombinant Bid by recombinant active caspase-8 could be blocked by anti-p10 and anti-p18 specific antibodies. Fas receptors could be similarly internalized into cytoplasm in type I and type II cells. Interestingly, p10 subunit of active caspase-8 could be detected in both type I and II cells, while p18 subunit of active caspase-8 could be detected only in type II cells but not in type I cells. These results demonstrated that p18 subunit was necessary for Bid cleavage and the mitochondria pathway might be dependent on the release of p18 subunit from active caspase-8.

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References

  1. Chinnaiyan AM, O’Rourke K, Tewari M et al (1995) FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 81(4):505–512

    Article  CAS  PubMed  Google Scholar 

  2. Muzio M, Chinnaiyan AM, Kischkel FC 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(6):817–827

    Article  CAS  PubMed  Google Scholar 

  3. Yang X, Chang HY, Baltimore D (1998) Autoproteolytic activation of pro-caspases by oligomerization. Mol Cell 1(2):319–325. doi:10.1016/S1097-2765(00)80032-5

    Article  CAS  PubMed  Google Scholar 

  4. Chen M, Orozco A, Spencer DM et al (2002) Activation of initiator caspases through a stable dimeric intermediate. J Biol Chem 277(52):50761–50767

    Article  CAS  PubMed  Google Scholar 

  5. Donepudi M, Mac Sweeney A, Briand C et al (2003) Insights into the regulatory mechanism for caspase-8 activation. Mol Cell 11(2):543–549. doi:10.1016/S1097-2765(03)00059-5

    Article  CAS  PubMed  Google Scholar 

  6. Scaffidi C, Fulda S, Srinivasan A et al (1998) Two CD95 (APO-1/Fas) signaling pathways. EMBO J 17(6):1675–1687

    Article  CAS  PubMed  Google Scholar 

  7. Li H, Zhu H, Xu CJ et al (1998) Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94(4):491–501

    Article  CAS  PubMed  Google Scholar 

  8. Luo X, Budihardjo I, Zou H et al (1998) Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 94(4):481–490

    Article  CAS  PubMed  Google Scholar 

  9. Li P, Nijhawan D, Budihardjo I et al (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91(4):479–489

    Article  CAS  PubMed  Google Scholar 

  10. Gross A, Yin XM, Wang K et al (1999) Caspase cleaved BID targets mitochondria and is required for cytochrome c release, while BCL-XL prevents this release but not tumor necrosis factor-R1/Fas death. J Biol Chem 274(2):1156–1163

    Article  CAS  PubMed  Google Scholar 

  11. Liu X, Zou H, Slaughter C et al (1997) DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis. Cell 89(2):175–184

    Article  CAS  PubMed  Google Scholar 

  12. Grenet J, Teitz T, Wei T et al (1999) Structure and chromosome localization of the human CASP8 gene. Gene 226(2):225–232

    Article  CAS  PubMed  Google Scholar 

  13. Scaffidi C, Medema JP, Krammer PH et al (1997) FLICE is predominantly expressed as two functionally active isoforms, caspase-8/a and caspase-8/b. J Biol Chem 272(43):26953–26958

    Article  CAS  PubMed  Google Scholar 

  14. Boldin MP, Goncharov TM, Goltsev YV et al (1996) Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death. Cell 85(6):803–815

    Article  CAS  PubMed  Google Scholar 

  15. Himeji D, Horiuchi T, Tsukamoto H et al (2002) Characterization of caspase-8L: a novel isoform of caspase-8 that behaves as an inhibitor of the caspase cascade. Blood 99(11):4070–4078

    Article  CAS  PubMed  Google Scholar 

  16. Chang DW, Xing Z, Capacio VL et al (2003) Interdimer processing mechanism of procaspase-8 activation. EMBO J 22(16):4132–4142

    Article  CAS  PubMed  Google Scholar 

  17. Medema JP, Scaffidi C, Kischkel FC et al (1997) FLICE is activated by association with the CD95 death-inducing signaling complex (DISC). EMBO J 16(10):2794–2804

    Article  CAS  PubMed  Google Scholar 

  18. Lee KH, Feig C, Tchikov V et al (2006) The role of receptor internalization in CD95 signaling. EMBO J 25(5):1009–1023

    Article  CAS  PubMed  Google Scholar 

  19. Eramo A, Sargiacomo M, Ricci-Vitiani L et al (2004) CD95 death-inducing signaling complex formation and internalization occur in lipid rafts of type I and type II cells. Eur J Immunol 34(7):1930–1940. doi:10.1002/eji.200324786

    Article  CAS  PubMed  Google Scholar 

  20. Li Y, Dida F, Iwao A et al (2007) Cell cycle dependency of caspase activation in Fas-induced apoptosis in leukemia cells. Cancer Sci 98(8):1174–1183. doi:10.1111/j.1349-7006.2007.00523.x

    Article  CAS  PubMed  Google Scholar 

  21. Kisenge RR, Toyoda H, Kang J et al (2003) Expression of short-form caspase 8 correlates with decreased sensitivity to Fas-mediated apoptosis in neuroblastoma cells. Cancer Sci 94(7):598–605. doi:10.1111/j.1349-7006.2003.tb01489.x

    Article  CAS  PubMed  Google Scholar 

  22. Roucou X, Montessuit S, Antonsson B, Martinou JC (2002) Bax oligomerization in mitochondrial membranes requires tBid (caspase-8-cleaved Bid) and a mitochondrial protein. Biochem J 368(Pt 3):915–921

    Article  CAS  PubMed  Google Scholar 

  23. Milhas D, Cuvillier O, Therville N et al (2005) Caspase-10 triggers Bid cleavage and caspase cascade activation in FasL-induced apoptosis. J Biol Chem 280(20):19836–19842

    Article  CAS  PubMed  Google Scholar 

  24. Earnshaw WC, Martins LM, Kaufmann SH (1999) Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem 68:383–424. doi:10.1146/annurev.biochem.68.1.383

    Article  CAS  PubMed  Google Scholar 

  25. Jia SH, Parodo J, Kapus A et al (2008) Dynamic regulation of neutrophil survival through tyrosine phosphorylation or dephosphorylation of caspase-8. J Biol Chem 283(9):5402–5413

    Article  CAS  PubMed  Google Scholar 

  26. Cursi S, Rufini A, Stagni V et al (2006) Src kinase phosphorylates caspase-8 on Tyr380: a novel mechanism of apoptosis suppression. EMBO J 25(9):1895–1905

    Article  CAS  PubMed  Google Scholar 

  27. Alvarado-Kristensson M, Melander F, Leandersson K et al (2004) p38-MAPK signals survival by phosphorylation of caspase-8 and caspase-3 in human neutrophils. J Exp Med 199(4):449–458

    Article  CAS  PubMed  Google Scholar 

  28. Lavrik I, Krueger A, Schmitz I et al (2003) The active caspase-8 heterotetramer is formed at the CD95 DISC. Cell Death Differ 10(1):144–145. doi:10.1038/sj.cdd.4401156

    Article  CAS  PubMed  Google Scholar 

  29. Gonzalvez F, Gottlieb E (2007) Cardiolipin: setting the beat of apoptosis. Apoptosis 12(5):877–885. doi:10.1007/s10495-007-0718-8

    Article  CAS  PubMed  Google Scholar 

  30. Ott M, Zhivotovsky B, Orrenius S (2007) Role of cardiolipin in cytochrome c release from mitochondria. Cell Death Differ 14(7):1243–1247. doi:10.1038/sj.cdd.4402135

    Article  CAS  PubMed  Google Scholar 

  31. Lutter M, Fang M, Luo X (2000) Cardiolipin provides specificity for targeting of tBid to mitochondria. Nat Cell Biol 2(10):754–761. doi:10.1038/35036395

    Article  CAS  PubMed  Google Scholar 

  32. Gonzalvez F, Schug ZT, Houtkooper RH (2008) Cardiolipin provides an essential activating platform for caspase-8 on mitochondria. J Cell Biol 183(4):681–696

    Article  CAS  PubMed  Google Scholar 

  33. Scorrano L (2008) Caspase-8 goes cardiolipin: a new platform to provide mitochondria with microdomains of apoptotic signals? J Cell Biol 183(4):579–581

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

This study was supported in part by Grants from the Ministry of Education, Science, Sports and Culture, Japan.

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Correspondence to Yoshihiro Komada.

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Li, Y., Qi, L., Iwao, A. et al. Alternative Fas-mediated cell death pathway is dependent on the different cleavage patterns of procaspase-8. Mol Cell Biochem 331, 231–238 (2009). https://doi.org/10.1007/s11010-009-0164-8

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  • DOI: https://doi.org/10.1007/s11010-009-0164-8

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