MISC

2001年6月

MST, a physiological caspase substrate, highly sensitizes apoptosis both upstream and downstream of caspase activation

JOURNAL OF BIOLOGICAL CHEMISTRY
  • KK Lee
  • ,
  • T Ohyama
  • ,
  • N Yajima
  • ,
  • S Tsubuki
  • ,
  • S Yonehara

276
22
開始ページ
19276
終了ページ
19285
記述言語
英語
掲載種別
DOI
10.1074/jbc.M005109200
出版者・発行元
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

The human serine/threonine kinase, mammalian STE20-like kinase (MST), is considerably homologous to the budding yeast kinases, SPS1 and STE20, throughout their kinase domains. The cellular function and physiological activation mechanism of MST is unknown except for the proteolytic cleavage-induced activation in apoptosis, In this study, we show that MST1 and MST2 are direct substrates of caspase-3 both in vivo and in vitro. cDNA cloning of MST homologues in mouse and nematode shows that caspase-cleaved sequences are evolutionarily conserved. Human MST1 has two caspase-cleavable sites, which generate biochemically distinct catalytic fragments, Staurosporine activates MST either caspase-dependently or independently, whereas Fas ligation activates it only caspase-dependently. Immunohistochemical analysis reveals that MST is localized in the cytoplasm, During Fas-mediated apoptosis, cleaved MST translocates into the nucleus before nuclear fragmentation is initiated, suggesting it functions in the nucleus. Transiently expressed MST1 induces striking morphological changes characteristic of apoptosis in both nucleus and cytoplasm, which is independent of caspase activation. Furthermore, when stably expressed in HeLa cells, MST highly sensitizes the cells to death receptor-mediated apoptosis by accelerating caspase-3 activation. These findings suggest that MST1 and MST2 play a role in apoptosis both upstream and downstream of caspase activation.

Web of Science ® 被引用回数 : 150

リンク情報
DOI
https://doi.org/10.1074/jbc.M005109200
CiNii Articles
http://ci.nii.ac.jp/naid/80012421037
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/11278283
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000169091000086&DestApp=WOS_CPL

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