*nlm.life
			PubMed Journals: J Biol Chem

  Source:		PMID: 9593687


    		J Biol Chem. 1998 May 29;273(22):13524-30.
     
			Caspase-mediated cleavage of the ubiquitin-protein
			ligase Nedd4 during apoptosis.

			Harvey KF(1), Harvey NL, Michael JM, Parasivam
			G, Waterhouse N, Alnemri ES, Watters D,
			Kumar S.

			Author Information
			(1) Hanson Centre for Cancer Research, Institute
			of Medical and Veterinary Science, Frome
			Road, Adelaide, SA 5000, Australia.

			The onset of apoptosis is coupled to the proteolytic
			activation of a family of cysteine proteases,
			termed caspases. These proteases cleave
			their target proteins after an aspartate
			residue. Following caspase activation during
			apoptosis, a number of specific proteins
			have been shown to be cleaved. Here we show
			that Nedd4, a ubiquitin-protein ligase containing
			multiple WW domains and a calcium/lipid-binding
			domain, is also cleaved during apoptosis
			induced by a variety of stimuli including
			Fas-ligation, gamma-radiation,
			tumor necrosis factor-alpha, C-8 ceramide, and
			etoposide treatment. Extracts from apoptotic
			cells also generated cleavage patterns similar
			to that seen in vivo, and this cleavage
			was inhibited by an inhibitor of caspase-3-like
			proteases. In vitro, Nedd4 was cleaved by
			a number of caspases, including caspase-1,
			-3, -6, and -7. By site-directed mutagenesis,
			one of the in vitro caspase cleavage sites
			in mouse Nedd4 was mapped to a DQPD237 downward
			arrow sequence, which is conserved between
			mouse, rat, and human proteins. This is
			the first report demonstrating that an enzyme
			of the ubiquitin pathway is cleaved by caspases
			during apoptosis.

			PMID: 9593687 [Indexed for MEDLINE]

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