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Caspase-2 primers cancer cells for TRAIL-mediated apoptosis by processing procaspase-8

Authors
 Soonah Shin ; Yoonmi Lee ; Wooseok Kim ; Hyeonseok Ko ; Hyeyeon Choi ; Kunhong Kim 
Citation
 EMBO Journal, Vol.24.0(20) : 3532~3542, 2005 
Journal Title
 EMBO Journal 
ISSN
 0261-4189 
Issue Date
2005
Abstract
Although caspase-2 is believed to be involved in death receptor-mediated apoptosis, the exact function, mode of activation, and regulation of caspase-2 remain unknown. Here we show that protein kinase (PK) CK2 phosphorylates procaspase-2 directly at serine-157. When intracellular PKCK2 activity is low or downregulated by specific inhibitors, procaspase-2 is dephosphorylated, dimerized, and activated in a PIDDosome-independent manner. The activated caspase-2 then processes procaspase-8 monomers between the large and small subunits, thereby priming cancer cells for TNF-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. The processed procaspase-8 that is recruited to death-inducing signaling complex by TRAIL engagement becomes fully activated, and cancer cells undergo apoptosis. PKCK2 activity is low in TRAIL-sensitive cancer cell lines but high in TRAIL-resistant cancer cell lines. Thus, downregulating PKCK2 activity is required for TRAIL-mediated apoptosis to occur in TRAIL-resistant cancer cells. Our data provide novel insights into the regulation, mode of activation, and function of caspase-2 in TRAIL-mediated apoptosis.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/147683
DOI
10.1038/sj.emboj.7600827
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Biochemistry & Molecular Biology
Yonsei Authors
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