Caspase-mediated cleavage of TRAF3 in FasL-stimulated Jurkat-T cells.
The tumor necrosis factor receptor (TNFR)-associated factor (TRAF) proteins play a central role in the early steps of signal transduction by TNFR superfamily proteins, which induce various cellular responses, including apoptosis. Influences of TRAF proteins on the regulation of cell death and physical interactions between TRAFs and caspases have been reported. In this study, we demonstrate that TRAF3 is proteolyzed during cell death in a caspase-dependent manner. TRAF3 was found to be cleaved by incubation with caspase3 in vitro and by Fas- or CD3-triggering in Jurkat-T cells. The Fas- or CD3-induced cleavage of TRAF3 was blocked by caspase inhibitors and by introduction of alanine substitutions for D347 and D367 residues. Furthermore, the amino-terminal fragment of TRAF3 showed a different intracellular localization from the full-length TRAF3 with preferential distribution to particulate fractions and the nucleus. These findings suggest that TRAF3 may be regulated by caspases during apoptosis of T cells.
Lee
Z H
ZH
National Research Laboratory for Bone Metabolism and Research Center for Proteineous Materials, Chosun University School of Dentistry, Kwangju, Korea.
Lee
S E
SE
Kwack
K
K
Yeo
W
W
Lee
T H
TH
Bae
S S
SS
Suh
P G
PG
Kim
H H
HH
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D019556:COS Cells / Q000201:enzymology / Q000378:metabolism; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors; D053222:Fas Ligand Protein; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D016853:Muromonab-CD3 / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D048008:TNF Receptor-Associated Factor 3
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D016853:Muromonab-CD3; D009842:Oligopeptides; D011506:Proteins; D011994:Recombinant Proteins; D048008:TNF Receptor-Associated Factor 3; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases