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J. Biol. Chem., Vol. 278, Issue 33, 30896-30904, August 15, 2003

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Ybp1 Is Required for the Hydrogen Peroxide-induced Oxidation of the Yap1 Transcription Factor^*

Elizabeth A. Veal , Sarah J. Ross  , Panagiota Malakasi, Emma Peacock and Brian A. Morgan ¶

From the School of Cell and Molecular Biosciences, Faculty of Medical Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kingdom

We describe the characterization of Ybp1, a novel protein, in Saccharomyces cerevisiae, that is required for the oxidative stress response to peroxides. Ybp1 is required for H₂O₂-induced expression of the antioxidant encoding gene TRX2. Our data indicate that the effects of Ybp1 are mediated through the Yap1 transcription factor. Indeed, Ybp1 forms a stress-induced complex with Yap1 in vivo and stimulates the nuclear accumulation of Yap1 in response to H₂O₂ but not in response to the thiol-oxidizing agent diamide. The H₂O₂-induced nuclear accumulation of Yap1 is regulated by the oxidation of specific cysteine residues and is dependent on the thiol peroxidase Gpx3. Our data suggest that Ybp1 is required for the H₂O₂-induced oxidation of Yap1 and acts in the same pathway as Gpx3. Consequently, Ybp1 represents a novel class of stress regulator of Yap1. These data have important implications for the regulation of protein oxidation and stress responses in eukaryotes.

Received for publication, April 4, 2003 , and in revised form, May 9, 2003.

^* This work was supported by the Medical Research Council, a Ph.D. Research Studentship (S. J. R.), and a Career Establishment Award (to B. A. M.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

These authors contributed equally to the work.

Present address: Cancer Research UK London Research Institute, Lincoln's Inn Fields, P. O. Box 123, 61 Lincoln's Inn Fields, London WC2 3PX, United Kingdom.

^¶ To whom correspondence should be addressed. Tel.: 191-222-7694; Fax: 191-222-7424; E-mail: b.a.morgan{at}ncl.ac.uk.

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