Format

Send to

Choose Destination
J Cell Biol. 2017 Sep 4;216(9):2843-2858. doi: 10.1083/jcb.201611170. Epub 2017 Jul 19.

TRIM37, a novel E3 ligase for PEX5-mediated peroxisomal matrix protein import.

Author information

1
Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA.
2
Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA ssubramani@ucsd.edu.

Abstract

Most proteins destined for the peroxisomal matrix depend on the peroxisomal targeting signals (PTSs), which require the PTS receptor PEX5, whose deficiency causes fatal human peroxisomal biogenesis disorders (PBDs). TRIM37 gene mutations cause muscle-liver-brain-eye (mulibrey) nanism. We found that TRIM37 localizes in peroxisomal membranes and ubiquitylates PEX5 at K464 by interacting with its C-terminal 51 amino acids (CT51), which is required for PTS protein import. PEX5 mutations (K464A or ΔCT51), or TRIM37 depletion or mutation, reduce PEX5 abundance by promoting its proteasomal degradation, thereby impairing its functions in cargo binding and PTS protein import in human cells. TRIM37 or PEX5 depletion induces apoptosis and enhances sensitivity to oxidative stress, underscoring the cellular requirement for functional peroxisomes. Therefore, TRIM37-mediated ubiquitylation stabilizes PEX5 and promotes peroxisomal matrix protein import, suggesting that mulibrey nanism is a new PBD.

PMID:
28724525
PMCID:
PMC5584156
DOI:
10.1083/jcb.201611170
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center