Ubiquitin Receptor Proteins hHR23a and hPLIC2 Interact

Yang Kang, Naixia Zhang, Deanna M. Koepp, Kylie J. Walters

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Ubiquitin receptor proteins play an important role in delivering ubiquitylated protein substrates to the proteasome for degradation. HHR23a and hPLIC2 are two such ubiquitin receptors that contain ubiquitin-like (UBL) domains, which interact with the proteasome, and ubiquitin-associated (UBA) domains, which interact with ubiquitin. Depending on their abundance UBL/UBA family members can either promote or inhibit the degradation of other proteins, which suggests their participation in the delivery of substrates to the proteasome is highly regulated. In previous work, we determined UBL/UBA domain interactions to promote intramolecular interactions in hHR23a that are abrogated with the addition of either ubiquitin or the proteasome component S5a. In yeast, we determined the hHR23a ortholog (Rad23) to interact with another UBL/UBA family member (Ddi1) and to bind a common tetraubiquitin chain. Here, we use NMR spectroscopy to reveal that hHR23a interacts with hPLIC2 via UBL/UBA domain interactions and to map their binding surfaces. In addition, we demonstrate that these two proteins associate in mammalian cells. Intriguingly, inhibition of the proteasome mitigates hHR23a/hPLIC2 interaction.

Original languageEnglish (US)
Pages (from-to)1093-1101
Number of pages9
JournalJournal of Molecular Biology
Volume365
Issue number4
DOIs
StatePublished - Jan 26 2007

Bibliographical note

Funding Information:
We are grateful to Dr Peter M. Howley and Dr Maurits Kleijnen for useful discussions and for providing us with anti-hPLIC2 antibody and hPLIC2 DNA constructs. NMR data were acquired in the NMR facility of the UMN and we thank Dr David Live and Dr Beverly Ostrowsky for their technical assistance. Data processing and visualization occurred in the Minnesota Supercomputing Institute Basic Sciences Computing Lab. This work was funded by grants from the National Institutes of Health CA097004 (to K.J.W.), Minnesota Medical Foundation (NMR facility), NSF BIR-961477 (NMR facility).

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

Keywords

  • hHR23a
  • hPLIC2
  • proteasome-mediated protein degradation
  • ubiquitin receptor proteins
  • ubiquitin-associated domains

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