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Molecular and Cellular Biology, April 2009, p. 1694-1706, Vol. 29, No. 7
0270-7306/09/$08.00+0     doi:10.1128/MCB.01470-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Quality Control of a Transcriptional Regulator by SUMO-Targeted Degradation{triangledown}

Zheng Wang and Gregory Prelich*

Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461

Received 18 September 2008/ Returned for modification 12 November 2008/ Accepted 5 January 2009

Slx5 and Slx8 are heterodimeric RING domain-containing proteins that possess SUMO-targeted ubiquitin ligase (STUbL) activity in vitro. Slx5-Slx8 and its orthologs are proposed to target SUMO conjugates for ubiquitin-mediated proteolysis, but the only in vivo substrate identified to date is mammalian PML, and the physiological importance of SUMO-targeted ubiquitylation remains largely unknown. We previously identified mutations in SLX5 and SLX8 by selecting for suppressors of a temperature-sensitive allele of MOT1, which encodes a regulator of TATA-binding protein. Here, we demonstrate that Mot1 is SUMOylated in vivo and that disrupting the Slx5-Slx8 pathway by mutation of the target lysines in Mot1, by deletion of SLX5 or the ubiquitin E2 UBC4, or by inhibition of the proteosome suppresses mot1-301 mutant phenotypes and increases the stability of the Mot1-301 protein. The Mot1-301 mutant protein is targeted for proteolysis by SUMOylation to a much greater extent than wild-type Mot1, suggesting a quality control mechanism. In support of this idea, growth of Saccharomyces cerevisiae in the presence of the arginine analog canavanine results in increased SUMOylation and Slx5-Slx8-mediated degradation of wild-type Mot1. These results therefore demonstrate that Mot1 is an in vivo STUbL target in yeast and suggest a role for SUMO-targeted degradation in protein quality control.

* Corresponding author. Mailing address: Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461. Phone: (718) 430-2181. Fax: (718) 430-8778. E-mail: prelich{at}aecom.yu.edu

{triangledown} Published ahead of print on 12 January 2009.

Molecular and Cellular Biology, April 2009, p. 1694-1706, Vol. 29, No. 7
0270-7306/09/$08.00+0     doi:10.1128/MCB.01470-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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