A Mechanism for Protein Monoubiquitination Dependent on a trans-Acting Ubiquitin-binding Domain*

Background: The mechanisms by which ubiquitin chain length is regulated remain largely unknown. Results: A ubiquitin-binding domain (UBD) acts in trans to direct substrate monoubiquitination in vitro. Conclusion: UBD binding to the first conjugated ubiquitin prevents further polyubiquitination. Significance: We report a new mechanism to control ubiquitin chain elongation. The length of the ubiquitin chain on a substrate dictates various functional outcomes, yet little is known about its regulation in vivo. The yeast arrestin-related protein Rim8/Art9 is monoubiquitinated in vivo by the Rsp5 ubiquitin ligase. This also requires Vps23, a protein that displays an ubiquitin-E2 variant (UEV) domain. Here, we report that binding of the UEV domain to Rim8 interferes with ubiquitin chain elongation and directs Rim8 monoubiquitination. We propose that Vps23 UEV competes with Rsp5 HECT N-lobe for binding to the first conjugated ubiquitin, thereby preventing polyubiquitination. These findings reveal a novel mechanism to control ubiquitin chain length on substrates in vivo.

• Publication year

  2013

• Venue

  Journal of Biological Chemistry

• Publication date

  2013-05-03

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.C113.452250PMID 23645667PMCID PMC3675560
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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