Ubiquitination of substrates by esterification

Xiaoli Wang, Roger A. Herr, Ted H. Hansen

Research output: Contribution to journalReview articlepeer-review

60 Scopus citations


Post-translational modification by ubiquitination determines intracellular location and fate of numerous proteins, thus impacting a diverse array of physiologic functions. Past dogma has been that ubiquitin was only coupled to substrates by isopeptide bonds to internal lysine residues or less frequently peptide bonds to the N-terminus. Enigmatically, however, several proteins lacking lysines had been reported to retain ubiquitin-dependent fates. Resolution of this paradox was afforded by recent observations that ubiquitination of substrates can also occur on cysteine or serine and threonine residues by thio- or oxy-ester bond formation, respectively (collectively called esterification). Although chemically possible, these bonds were considered too labile to be of physiological relevance. In this review we discuss recent evidence for the ubiquitination of protein substrates by esterification and speculate on its mechanism and its physiological importance.

Original languageEnglish
Pages (from-to)19-24
Number of pages6
Issue number1
StatePublished - Jan 2012


  • ER-associated degradation
  • Esterification
  • Oxyester bond
  • Thioester bond
  • Ubiquitin
  • Ubiquitin conjugating enzyme
  • Ubiquitin protein ligase
  • Ubiquitin-dependent degradation
  • Ubiquitination


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