Reactome | TRAF1 is cleaved by caspases

TRAF1 is cleaved by caspases

Stable Identifier

R-HSA-5634228

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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).

Literature References

PubMed ID	Title	Journal	Year
12709429	Caspase-mediated cleavage converts the tumor necrosis factor (TNF) receptor-associated factor (TRAF)-1 from a selective modulator of TNF receptor signaling to a general inhibitor of NF-kappaB activation Henkler, F, Baumann, B, Fotin-Mleczek, M, Weingärtner, M, Schwenzer, R, Peters, N, Graness, A, Wirth, T, Scheurich, P, Schmid, JA, Wajant, H	J. Biol. Chem.	2003
11098060	TRAF1 is a substrate of caspases activated during tumor necrosis factor receptor-alpha-induced apoptosis Leo, E, Deveraux, QL, Buchholtz, C, Welsh, K, Matsuzawa, S, Stennicke, HR, Salvesen, GS, Reed, JC	J. Biol. Chem.	2001