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			PubMed Journals: J Biol Chem

  Source:		PMID: 12198130


    		J Biol Chem. 2002 Nov 8;277(45):42769-74.
     		Epub 2002 Aug 26.

			Phosphorylation of Nrf2 at Ser-40 by protein
			kinase C regulates antioxidant response
			element-mediated transcription.

			Huang HC(1), Nguyen T, Pickett CB.

			Author Information
			(1) Schering-Plough Research Institute,
			Kenilworth, New Jersey 07033, USA.

			Nrf2, a basic leucine zipper transcription
			factor, is an essential activator of the
			coordinated transcription of genes encoding
			antioxidant enzymes and phase II detoxifying
			enzymes through the regulatory sequence
			termed antioxidant response element (ARE).
			Recently we reported evidence for the involvement
			of protein kinase C (PKC) in phosphorylating
			Nrf2 and triggering its nuclear translocation
			in response to oxidative stress. We show
			here that phosphorylation of purified rat
			Nrf2 by the catalytic subunit of PKC was
			blocked by a synthetic peptide mimicking
			one of the potential PKC sites. Accordingly,
			Nrf2 bearing a Ser to Ala mutation at amino
			acid 40 (S40A) could not be phosphorylated
			by PKC. The S40A mutation did not affect
			in vitro binding of Nrf2/MafK to the ARE.
			However, it partially impaired Nrf2 activation
			of ARE-driven transcription in a reporter
			gene assay when Keap1 was overexpressed.
			In vitro transcribed/translated Keap1 could
			be coimmunoprecipitated with Nrf2. Phosphorylation
			of wild-type Nrf2 by PKC promoted its dissociation
			from Keap1, whereas the Nrf2-S40A mutant
			remained associated. These findings together
			with our prior studies suggest that the
			PKC-catalyzed phosphorylation of Nrf2 at
			Ser-40 is a critical signaling event leading
			to ARE-mediated cellular antioxidant response.

			DOI: 10.1074/jbc.M206911200 PMID: 12198130
			[Indexed for MEDLINE]

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