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			PubMed Journals: J Biol Chem

  Source:		PMID: 11278572


    		J Biol Chem. 2001 Jun 1;276(22):19656-63.
     		Epub 2001 Mar 13.

			Cdc42 is a substrate for caspases and influences
			Fas-induced apoptosis.

			Tu S(1), Cerione RA.

			Author Information
			(1) Department of Molecular Medicine, Veterinary
			Medical Center, Baker Laboratory,
			Cornell University, Ithaca, New York, 14853,
			USA.

			Fas-mediated apoptosis results in the activation
			of caspases, which subsequently cleave cellular
			substrates that are essential for normal
			cell viability. In the present study, we
			show that the Ras-related GTP-binding protein
			Cdc42 is susceptible to caspase-catalyzed
			proteolysis in a number of cell lines, including
			NIH3T3 fibroblasts, human breast cancer
			cells (e.g. T47D), and COS-7 cells. Both
			caspase-3 and caspase-7 were able to catalyze
			the cleavage of Cdc42, whereas caspase-6
			and caspase-8 were without effect. The
			susceptibility to the caspase-stimulated
			degradation is specific; although Rac can
			also serve as a caspase substrate, neither
			Rho nor Ras is degraded. Caspase sensitivity
			is conferred by a consensus sequence (DXXD)
			that lies immediately upstream of the Rho
			insert regions (residues 122-134) of Cdc42
			and Rac. The removal of a stretch of residues
			(120) that includes the insert region or
			site-directed mutagenesis of either aspartic
			acid 118 or 121 within a constitutively
			active background (i.e. Cdc42(F28L)) as
			well as a wild-type Cdc42 background yields
			Cdc42 molecules that provide a marked protection
			against Fas ligand-induced apoptosis. Overall,
			these results are consistent with a model
			in which Cdc42 acts downstream of Fas, perhaps
			to influence the rate of apoptosis, with
			the ultimate caspase-mediated degradation
			of Cdc42 then allowing for a maximal apoptotic
			response.

			DOI: 10.1074/jbc.M009838200 PMID: 11278572
			[Indexed for MEDLINE]

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