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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(20) : 3532-3542, 2005 
Journal Title
 EMBO JOURNAL 
ISSN
 0261-4189 
Issue Date
2005
MeSH
Apoptosis* ; Apoptosis Regulatory Proteins/pharmacology ; Casein Kinase II/antagonists & inhibitors ; Casein Kinase II/genetics ; Casein Kinase II/metabolism* ; Caspase 2 ; Caspase 8 ; Caspases/genetics ; Caspases/metabolism* ; Cell Line ; Tumor ; Dimerization ; Enzyme Activation ; Humans ; Membrane Glycoproteins/pharmacology ; Neoplasms/enzymology* ; Phosphorylation ; Serine/metabolism ; TNF-Related Apoptosis-Inducing Ligand ; Tumor Necrosis Factor-alpha/pharmacology
Keywords
caspase-2 ; caspase-8 ; PKCK2 ; priming ; TRAIL
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.
Files in This Item:
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DOI
10.1038/sj.emboj.7600827
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kun Hong(김건홍) ORCID logo https://orcid.org/0000-0001-5639-6372
Shin, Soonah(신순아)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/147683
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