Format

Send to

Choose Destination
Curr Biol. 2005 Jun 7;15(11):1058-64.

HSJ1 is a neuronal shuttling factor for the sorting of chaperone clients to the proteasome.

Author information

1
Institute for Cell Biology, Rheinische Friedrich-Wilhelms University Bonn, Ulrich-Haberland-Strasse 61a, D-53121 Bonn, Germany.

Abstract

Protein degradation in eukaryotic cells usually involves the attachment of a ubiquitin chain to a substrate protein and its subsequent sorting to the proteasome. Molecular mechanisms underlying the sorting process only recently began to emerge and rely on a cooperation of chaperone machineries and ubiquitin-chain recognition factors [1-3]. Here, we identify isoforms of the cochaperone HSJ1 as neuronal shuttling factors for ubiquitylated proteins. HSJ1 combines a J-domain that stimulates substrate loading onto the Hsc70 chaperone with ubiquitin interaction motifs (UIMs) involved in binding ubiquitylated chaperone clients. HSJ1 prevents client aggregation, shields clients against chain trimming by ubiquitin hydrolases, and stimulates their sorting to the proteasome. In this way, HSJ1 isoforms participate in ER-associated degradation (ERAD) and protect neurons against cytotoxic protein aggregation.

PMID:
15936278
DOI:
10.1016/j.cub.2005.04.058
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center