The role of CAP3 in CD95 signaling: New insights into the mechanism of procaspase-8 activation

A. Golks, D. Brenner, I. Schmitz, C. Watzl, A. Krueger, P. H. Krammer*, I. N. Lavrik

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

27 Citations (Scopus)

Abstract

Formation of the CD95 (APO-1/Fas) death inducing signaling complex (DISC) plays a central role in CD95 signaling. Previously, CD95 DISC composition was analyzed by two-dimensional gel electrophoresis and four major cytotoxicity-associated proteins (CAP1/4) were found. CAP1 and CAP2 were defined to be unmodified and phosphorylated FADD, respectively. CAP4 was identified as procaspase-8a. CAP3, however, has remained elusive. In this study, we demonstrate that CAP3 is an intermediate of procaspase-8 processing. CAP3 is generated within seconds of DISC formation and subsequently processed to the prodomain of procaspase-8a that is known as p26 (CAP5). These findings lead to new insights into the mechanism of procaspase-8 processing and apoptosis initiation.

Original languageEnglish
Pages (from-to)489-498
Number of pages10
JournalCell Death and Differentiation
Volume13
Issue number3
DOIs
Publication statusPublished - Mar 2006
Externally publishedYes

Keywords

  • Apoptosis
  • CAP3
  • CD95

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