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			PubMed Journals: J Biol Chem

  Source:		PMID: 11278283


    		J Biol Chem. 2001 Jun 1;276(22):19276-85.
     		Epub 2001 Mar 7.

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

			Lee KK(1), Ohyama T, Yajima N, Tsubuki S,
			Yonehara S.

			Author Information
			(1) Institute for Virus Research, Kyoto University,
			Kyoto 606-8507, Japan.

			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.

			DOI: 10.1074/jbc.M005109200 PMID: 11278283
			[Indexed for MEDLINE]

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