USE1 is a bispecific conjugating enzyme for ubiquitin and FAT10, which FAT10ylates itself in cis

The ubiquitin-like modifier FAT10 targets proteins for degradation by the proteasome and is activated by the E1 enzyme UBA6. In this study, we identify the UBA6-specific E2 enzyme (USE1) as an interaction partner of FAT10. Activated FAT10 can be transferred from UBA6 onto USE1 in vitro , and endogen...

Full description

Saved in:
Bibliographic Details
Published in:Nature communications 2010-05, Vol.1 (2), p.1-10, Article 13
Main Authors: Groettrup, Marcus, Aichem, Annette, Pelzer, Christiane, Lukasiak, Sebastian, Kalveram, Birte, Sheppard, Paul W, Rani, Neha, Schmidtke, Gunter
Format: Article
Language:English
Subjects:
631/208/2490
631/337
631/45
HEK293 Cells
Humanities and Social Sciences
Humans
multidisciplinary
Protein Binding - genetics
Protein Binding - physiology
RNA, Small Interfering
Science
Science (multidisciplinary)
Two-Hybrid System Techniques
Ubiquitin - genetics
Ubiquitin - metabolism
Ubiquitins - genetics
Ubiquitins - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The ubiquitin-like modifier FAT10 targets proteins for degradation by the proteasome and is activated by the E1 enzyme UBA6. In this study, we identify the UBA6-specific E2 enzyme (USE1) as an interaction partner of FAT10. Activated FAT10 can be transferred from UBA6 onto USE1 in vitro , and endogenous USE1 and FAT10 can be coimmunoprecipitated from intact cells. Small interfering RNA-mediated downregulation of USE1 mRNA resulted in a strong reduction of FAT10 conjugate formation under endogenous conditions, suggesting that USE1 is a major E2 enzyme in the FAT10 conjugation cascade. Interestingly, USE1 is not only the first E2 enzyme but also the first known substrate of FAT10 conjugation, as it was efficiently auto-FAT10ylated in cis but not in trans . The ubiquitin-like modifier FAT10 targets proteins for proteolytic degradation. Here the ubiquitin-conjugating enzyme USE1 is identified as a component of the FAT10 conjugation cascade.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms1012