title: Caspase-3-mediated cleavage of PICOT in apoptosis.
abstract: Mammalian protein kinase C-interacting cousin of thioredoxin (PICOT) is a multi-domain mono-thiol glutaredoxin that is involved in several signal transduction pathways and is necessary for cell growth and metastasis. Here, we demonstrate that PICOT is a cleavage substrate of the apoptosis-related protein caspase-3. In vitro cleavage assays indicated that PICOT was specifically cleaved by caspase-3. Similarly, endogenous PICOT was cleaved in cell death responses induced by staurosporine and etoposide. These phenomena were blocked in the presence of a pan-caspase inhibitor. Using site-directed mutagenesis, we identified two putative caspase-3 cleavage sequences in PICOT, DRLD(101)/G and EELD(226)/T. Interestingly, overexpression of either PICOT wild type or the D101A/D226A double point mutant accelerated etoposide-induced activation of caspase-3 whereas siRNA-mediated knockdown of PICOT blocked this phenomenon. Our data raise the possibility that the pro-apoptotic role of PICOT is actively regulated via caspase-3-mediated cleavage.
authors: Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749, Republic of Korea.
authors: Nuri
authors: N
authors: Yun
authors: Chiho
authors: C
authors: Kim
authors: Hyeseon
authors: H
authors: Cha
authors: Woo Jin
authors: WJ
authors: Park
authors: Hirohiko
authors: H
authors: Shibayama
authors: Il-Seon
authors: IS
authors: Park
authors: Young J
authors: YJ
authors: Oh
mesh_terms: D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D051379:Mice
chemical_list: D002352:Carrier Proteins; C404105:GLRX3 protein, human; D053148:Caspase 3