Ube2j2 ubiquitinates hydroxylated amino acids on ER-associated degradation substrates

Xiaoli Wang, Roger A. Herr, Martijn Rabelink, Rob C. Hoeben, Emmanuel J.H.J. Wiertz, Ted H. Hansen

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Ubiquitin (Ub) modification of proteins plays a prominent role in the regulation of multiple cell processes, including endoplasmic reticulum-associated degradation (ERAD). Until recently, ubiquitination of substrates was thought to occur only via isopeptide bonds, typically to lysine residues. Several recent studies suggest that Ub can also be coupled to nonlysine residues by ester/thiolester bonds; however, the molecular basis for these novel modifications remains elusive. To probe the mechanism and importance of nonlysine ubiquitination, we have studied the viral ligase murine K3 (mK3), which facilitates the polyubiquitination of hydroxylated amino acids serine/threonine on its ERAD substrate. In this paper, we identify Ube2j2 as the primary cellular E2 recruited by the mK3 ligase, and this E2-E3 pair is capable of conjugating Ub on lysine or serine residues of substrates. However, surprisingly, Ube2j2-mK3 preferentially promotes ubiquitination of hydroxylated amino acids via ester bonds even when lysine residues are present on wild-type substrates, thus establishing physiological relevance of this novel ubiquitination strategy.

Original languageEnglish
Pages (from-to)655-668
Number of pages14
JournalJournal of Cell Biology
Volume187
Issue number5
DOIs
StatePublished - Nov 30 2009

Fingerprint Dive into the research topics of 'Ube2j2 ubiquitinates hydroxylated amino acids on ER-associated degradation substrates'. Together they form a unique fingerprint.

  • Cite this

    Wang, X., Herr, R. A., Rabelink, M., Hoeben, R. C., Wiertz, E. J. H. J., & Hansen, T. H. (2009). Ube2j2 ubiquitinates hydroxylated amino acids on ER-associated degradation substrates. Journal of Cell Biology, 187(5), 655-668. https://doi.org/10.1083/jcb.200908036