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Quality control of a transcriptional regulator by SUMO-targeted degradation.

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.

Pubmed ID: 19139279

Authors

  • Wang Z
  • Prelich G

Journal

Molecular and cellular biology

Publication Data

April 12, 2009

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM52486

Mesh Terms

  • Adenosine Triphosphatases
  • Amino Acid Sequence
  • Canavanine
  • DNA Helicases
  • Molecular Sequence Data
  • Mutant Proteins
  • Mutation
  • Phenotype
  • Proteasome Endopeptidase Complex
  • Protein Processing, Post-Translational
  • Protein Stability
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Small Ubiquitin-Related Modifier Proteins
  • Substrate Specificity
  • TATA-Binding Protein Associated Factors
  • Transcription, Genetic
  • Ubiquitin