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	Mechanism of procaspase-8 activation by c-FLIPL
	Yu, Jong W. ; Jeffrey, Philip D. ; Shi, Yigong
	2010-10-12 ; 2010-10-12
关键词	apoptosis caspase-8 extrinsic pathway cellular FLICE-inhibitory protein KAPPA-B ACTIVATION SIGNALING COMPLEX CRYSTAL-STRUCTURE ALLOSTERIC SITE CELLULAR FLIP LONG FORM DEATH APOPTOSIS CASPASE-8 INHIBITION Multidisciplinary Sciences
中文摘要	Cellular FLICE-inhibitory protein (c-FLIPL) is a key regulator of the extrinsic cell death pathway. Although widely regarded as an inhibitor of initiator caspase activation and cell death, c-FLIPL is also capable of enhancing procaspase-8 activation through heterodimerization of their respective protease domains. However, the underlying mechanism of this activation process remains enigmatic. Here, we demonstrate that cleavage of the intersubunit linker of c-FLIPL by procaspase-8 potentiates the activation process by enhancing heterodimerization between the two proteins and vastly improving the proteolytic activity of unprocessed caspase-(C)8. The crystal structures of the protease-like domain of c-FLIPL alone and in complex with zymogen C8 identify the unique determinants that favor heterodimerization over procaspase-8 homodimerization, and induce the latent active site of zymogen C8 into a productive conformation. Together, these findings provide molecular insights into a key aspect of c-FLIPL function that modulates procaspase-8 activation to elicit diverse responses in different cellular contexts.
语种	英语 ; 英语
出版者	NATL ACAD SCIENCES ; WASHINGTON ; 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
内容类型	期刊论文
源URL	[http://hdl.handle.net/123456789/81832]
专题	清华大学
推荐引用方式 GB/T 7714	Yu, Jong W.,Jeffrey, Philip D.,Shi, Yigong. Mechanism of procaspase-8 activation by c-FLIPL[J],2010, 2010.
APA	Yu, Jong W.,Jeffrey, Philip D.,&Shi, Yigong.(2010).Mechanism of procaspase-8 activation by c-FLIPL..
MLA	Yu, Jong W.,et al."Mechanism of procaspase-8 activation by c-FLIPL".(2010).

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