Quality control of a transcriptional regulator by SUMO-targeted degradation

Zheng Wang, Gregory Prelich

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

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 M0T1, which encodes a regulator of TATA-binding protein. Here, we demonstrate that Motl is SUMOylated in vivo and that disrupting the Slx5-Slx8 pathway by mutation of the target lysines in Motl, by deletion of SLX5 or the ubiquitin E2 UBC4, or by inhibition of the proteosome suppresses motl-301 mutant phenotypes and increases the stability of the Motl-301 protein. The Motl-301 mutant protein is targeted for proteolysis by SUMOylation to a much greater extent than wild-type Motl, 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 Motl. These results therefore demonstrate that Motl is an in vivo STUbL target in yeast and suggest a role for SUMO-targeted degradation in protein quality control.

Original languageEnglish (US)
Pages (from-to)1694-1706
Number of pages13
JournalMolecular and Cellular Biology
Volume29
Issue number7
DOIs
StatePublished - Apr 2009

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Ubiquitin
Quality Control
Sumoylation
Proteolysis
Ligases
Small Ubiquitin-Related Modifier Proteins
Canavanine
TATA-Box Binding Protein
Mutation
Ubiquitination
Mutant Proteins
Lysine
Saccharomyces cerevisiae
Arginine
Yeasts
Alleles
Phenotype
Temperature
Growth
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Quality control of a transcriptional regulator by SUMO-targeted degradation. / Wang, Zheng; Prelich, Gregory.

In: Molecular and Cellular Biology, Vol. 29, No. 7, 04.2009, p. 1694-1706.

Research output: Contribution to journalArticle

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