Quality Control of a Transcriptional Regulator by SUMO-Targeted Degradation
- 1 April 2009
- journal article
- research article
- Published by Informa UK Limited in Molecular and Cellular Biology
- Vol. 29 (7), 1694-1706
- https://doi.org/10.1128/mcb.01470-08
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 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.Keywords
This publication has 58 references indexed in Scilit:
- SUMO modification of PCNA is controlled by DNAThe EMBO Journal, 2008
- Activation of the Slx5–Slx8 Ubiquitin Ligase by Poly-small Ubiquitin-like Modifier ConjugatesJournal of Biological Chemistry, 2008
- Stimulation of in vitro sumoylation by Slx5–Slx8: Evidence for a functional interaction with the SUMO pathwayDNA Repair, 2007
- Conserved function of RNF4 family proteins in eukaryotes: targeting a ubiquitin ligase to SUMOylated proteinsThe EMBO Journal, 2007
- SUMO-targeted ubiquitin ligases in genome stabilityThe EMBO Journal, 2007
- Insights into E3 ligase activity revealed by a SUMO–RanGAP1–Ubc9–Nup358 complexNature, 2005
- SUMO-modified PCNA recruits Srs2 to prevent recombination during S phaseNature, 2005
- Degradation-Mediated Protein Quality Control in the NucleusCell, 2005
- Sir Antagonist 1 (San1) Is a Ubiquitin LigasePublished by Elsevier BV ,2004
- Mot1 Regulates the DNA Binding Activity of Free TATA-binding Protein in an ATP-dependent MannerPublished by Elsevier BV ,2003