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PMID: 19951915 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Ube2j2 ubiquitinates hydroxylated amino acids on ER-associated degradation substrates.

The Journal of cell biology ·Vol. 187 ·No. 5 ·2009-11-30 ·Pages 655-68

Wang X, Herr RA, Rabelink M, Hoeben RC, Wiertz EJ, Hansen TH

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.

MeSH Terms
Amino Acid Sequence Animals Cell Line Endoplasmic Reticulum/metabolism Iron-Binding Proteins/genetics,metabolism,physiology Ligases/chemistry,genetics,physiology Major Histocompatibility Complex Mice Molecular Sequence Data Protein Structure, Tertiary Sequence Alignment Ubiquitin-Conjugating Enzymes/genetics,metabolism,physiology Ubiquitination
Chemicals
Iron-Binding Proteins UBE2J2 protein, mouse Ube2d1 protein, mouse Ubiquitin-Conjugating Enzymes Ligases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wang Xiaoli
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Herr Roger A
Rabelink Martijn
Hoeben Rob C
Wiertz Emmanuel J H J
Hansen Ted H
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.200908036
Published
2009-11-30
Pages
655-68
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2806592
Subset
IM
Grants
NIAID NIH HHS · R01 AI019687 · United States
NIAID NIH HHS · AI019687 · United States
External Links
PubMed source DOI: 10.1083/jcb.200908036 PMC Full Text View journal details
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