During TNF-alpha or Fas ligand-induced apoptosis TRAF1 can be processed into two fragments (Imler M et al. 2000; Leo E et al. 2001). Caspases-3, -6 and most efficiently caspase-8 cleave TRAF1 in vitro (Imler M et al. 2000; Leo E et al. 2001). Cleavage of TRAF1 occurs at the Asp-163 residue. A mutant TRAF1 (Asp163Ala) was not processed by either caspase (Imler M et al. 2000). The C-terminal cleavage product of TRAF1 was found to inhibit the induction of NFkB when co-expressed with NFkB inducers (such as TNFR1, DR3, TNFR2, Fas etc.) in human embryonic kidney 293 (HEK293) cells or upon treatment with TNF (Imler M et al. 2000; Henkler F et al. 2003). Furthermore, co-transfection of VSV-tagged IKKbeta and TRAF1(truncated or wild-type) into HEK293 or Jurkat T-cells followed by anti-VSV immunoprecipitation coupled with GST-IkB alpha immunocomplex kinase assays for IKK activity revealed that the caspase-generated TRAF1-fragment, but not TRAF1 itself inhibited IKK activation (Henkler F et al. 2003).
Schmid, JA, Schwenzer, R, Fotin-Mleczek, M, Scheurich, P, Wajant, H, Baumann, B, Graness, A, Weingärtner, M, Peters, N, Wirth, T, Henkler, F
Stennicke, HR, Matsuzawa, S, Deveraux, QL, Buchholtz, C, Reed, JC, Leo, E, Welsh, K, Salvesen, GS
cysteine-type endopeptidase activity of active caspase-8 [cytosol]
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