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Molecular and Cellular Biology, January 2006, p. 371-380, Vol. 26, No. 1
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.1.371-380.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

The Short-Lived Mat{alpha}2 Transcriptional Repressor Is Protected from Degradation In Vivo by Interactions with Its Corepressors Tup1 and Ssn6

Jeffrey D. Laney,1 Erika F. Mobley,1 and Mark Hochstrasser2*

Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Box G-J2, Providence, Rhode Island 02912,1 Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, P.O. Box 208114, New Haven, Connecticut 065202

Received 9 May 2005/ Returned for modification 18 July 2005/ Accepted 13 October 2005

The Mat{alpha}2 ({alpha}2) protein is a transcriptional repressor necessary for the proper expression of cell type-specific genes in Saccharomyces cerevisiae. Like many transcription factors, {alpha}2 is rapidly degraded in vivo by the ubiquitin-proteasome pathway. At least two different ubiquitin-dependent pathways target {alpha}2 for destruction, one of which recognizes the well-characterized Deg1 degradation determinant near the N terminus of the protein. Here we report that the {alpha}2 corepressors Tup1 and Ssn6 modify the in vivo degradation rate of {alpha}2. Tup1 modulates the metabolic stability of {alpha}2 by directly binding to the Deg1-containing region of the protein. TUP1 overexpression specifically stabilizes Deg1-containing proteins but not other substrates of the same ubiquitination enzymes that recognize Deg1. Point mutations in both {alpha}2 and Tup1 that compromise the {alpha}2-Tup1 binding interaction disrupt the ability of Tup1 to stabilize Deg1 proteins. The physical association between Tup1 and {alpha}2 competes with the ubiquitination machinery for access to the Deg1 signal. Finally, we observe that overproduction of both Tup1 and Ssn6, but not either alone, strongly stabilizes the endogenous {alpha}2 protein. From these results, we propose that the fraction of {alpha}2 found in active regulatory complexes with Tup1 and Ssn6 is spared from rapid proteolytic destruction and is stabilized relative to the uncomplexed pool of the protein.

* Corresponding author. Mailing address: Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, P.O. Box 208114, New Haven, CT 06520. Phone: (203) 432-5101. Fax: (203) 432-5175. E-mail: mark.hochstrasser{at}yale.edu.

Molecular and Cellular Biology, January 2006, p. 371-380, Vol. 26, No. 1
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.1.371-380.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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