Logo image
Back
The ER-resident ubiquitin-specific protease 19 participates in the UPR and rescues ERAD substrates
Journal article   Open access   Peer reviewed

The ER-resident ubiquitin-specific protease 19 participates in the UPR and rescues ERAD substrates

Gerco C. Hassink, Bin Zhao, Ramakrishna Sompallae, Mikael Altun, Stefano Gastaldello, Nikolay V. Zinin, Maria G. Masucci and Kristina Lindsten
EMBO reports, Vol.10(7), pp.755-761
07/2009
DOI: 10.1038/embor.2009.69
PMCID: PMC2727442
PMID: 19465887
url
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727442View
Published (Version of record) Open Access

Abstract

Ubiquitination regulates membrane events such as endocytosis, membrane trafficking and endoplasmic-reticulum-associated degradation (ERAD). Although the involvement of membrane-associated ubiquitin-conjugating enzymes and ligases in these processes is well documented, their regulation by ubiquitin deconjugases is less well understood. By screening a database of human deubiquitinating enzymes (DUBs), we have identified a putative transmembrane domain in ubiquitin-specific protease (USP) 19. We show that USP19 is a tail-anchored ubiquitin-specific protease localized to the ER and is a target of the unfolded protein response. USP19 rescues the ERAD substrates cystic fibrosis transmembrane conductance regulator (CFTR) Delta F508 and T-cell receptor-alpha (TCR alpha) from proteasomal degradation. A catalytically inactive USP19 was still able to partly rescue TCR alpha but not CFTR Delta F508, suggesting that USP19 might also exert a non-catalytic function on specific ERAD substrates. Thus, USP19 is the first example of a membrane-anchored DUB involved in the turnover of ERAD substrates.
 Biochemistry & Molecular Biology Cell Biology Life Sciences & Biomedicine Science & Technology

Details

Metrics

12 Record Views
126 Times Cited - Web of Science
Logo image