Protection from Isopeptidase-Mediated Deconjugation Regulates Paralog-Selective Sumoylation of RanGAP1

Shanshan Zhu, Jacqueline Goeres, Katherine M. Sixt, Miklós Békés, Xiang Dong Zhang, Guy S. Salvesen, Michael J Matunis

Research output: Contribution to journalArticle

Abstract

Vertebrates express three small ubiquitin-related modifiers (SUMO-1, SUMO-2, and SUMO-3) that are conjugated in part to unique subsets of proteins and, thereby, regulate distinct cellular processes. Mechanisms regulating paralog-selective sumoylation, however, remain poorly understood. Despite being equally well modified by SUMO-1 and SUMO-2 in vitro, RanGAP1 is selectively modified by SUMO-1 in vivo. We have found that this paralog-selective modification is determined at the level of deconjugation by isopeptidases. Our findings indicate that, relative to SUMO-2-modified RanGAP1, SUMO-1-modified RanGAP1 forms a more stable, higher affinity complex with the nucleoporin Nup358/RanBP2 that preferentially protects it from isopeptidases. By swapping residues in SUMO-1 and SUMO-2 responsible for Nup358/RanBP2 binding, or by manipulating isopeptidase expression levels, paralog-selective modification of RanGAP1 could be affected both in vitro and in vivo. Thus, protection from isopeptidases, through interactions with SUMO-binding proteins, represents an important mechanism defining paralog-selective sumoylation.

Original languageEnglish (US)
Pages (from-to)570-580
Number of pages11
JournalMolecular Cell
Volume33
Issue number5
DOIs
Publication statusPublished - Mar 13 2009

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Keywords

  • PROTEINS

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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