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The UBL domain of PLIC‐1 regulates aggresome formation
Author(s) -
Heir Renu,
Ablasou Celine,
Dumontier Emilie,
Elliott Meghan,
FagottoKaufmann Christine,
Bedford Fiona K
Publication year - 2006
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400823
Subject(s) - aggresome , ubiquitin , deubiquitinating enzyme , microbiology and biotechnology , chaperone (clinical) , protein subunit , ubiquitin ligase , gene knockdown , small hairpin rna , biology , chemistry , downregulation and upregulation , biochemistry , cell culture , genetics , medicine , pathology , gene
Defects in protein folding and the proteasomal pathway have been linked with many neurodegenerative diseases. PLIC‐1 (protein linking IAP to the cytoskeleton) is a ubiquitin‐like protein that binds to the ubiquitin‐interacting motif (UIM) of the proteasomal subunit S5a. Here, we show that PLIC‐1 also binds to the UIM proteins ataxin 3—a deubiquitinating enzyme—HSJ1a—a co‐chaperone—and EPS15 (epidermal growth factor substrate 15)—an endocytic protein. Using a polyglutamine (polyQ) disease model, we found that both endogenous PLIC‐1 and EPS15 localize to perinuclear aggresomes, and that polyQ enhances their in vivo interaction. We show that knockdown of PLIC‐1 and EPS15 by RNA interference reduces aggresome formation. In addition, PLIC‐1 ΔUBL functions as a dominant‐negative mutant, blocking both polyQ transport to aggresomes and the association of EPS15 with dispersed aggregates. We also show that PLIC‐1 is upregulated by arsenite‐induced protein misfolding. These results indicate a role for PLIC‐1 in the protein aggregation‐stress pathway, and we propose a novel function for the ubiquitin‐like (UBL) domain—by means of UBL–UIM interactions—in transport to aggresomes.