SUMO-mimicking peptides inhibiting protein SUMOylation

Bo Zhao, Eric B. Villhauer, Karan Bhuripanyo, Hiroaki Kiyokawa, Hermann Schindelin, Jun Yin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The ubiquitin-like protein SUMO is transferred through a core E1-E2 cascade composed of the SUMO-activating enzyme (SAE) and Ubc9 to modify cellular proteins and transmit important biological signals. SAE primarily recognizes the C-terminal tail of SUMO and catalyzes ATP condensation with the SUMO C-terminal carboxylate to activate its transfer through the cascade. Here, we used phage display to show that a broad profile of SUMO C-terminal sequences could be activated by SAE. Based on this, we developed heptamer peptides that could 1) form thioester conjugates with SAE, 2) be transferred from SAE to Ubc9, and 3) be further transferred to the SUMOylation target protein RanGAP1. As these peptides recapitulate the action of SUMO in protein modification, we refer to them as "SUMO-mimicking peptides". We found that, once the peptides were conjugated to SAE and Ubc9, they blocked full-length SUMO from entering the cascade. These peptides can thus function as mechanism-based inhibitors of the protein SUMOylation reaction.

Original languageEnglish (US)
Pages (from-to)2662-2666
Number of pages5
JournalChemBioChem
Volume15
Issue number18
DOIs
StatePublished - Nov 20 2014

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

Fingerprint Dive into the research topics of 'SUMO-mimicking peptides inhibiting protein SUMOylation'. Together they form a unique fingerprint.

Cite this