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EMBO reports 7, 12, 1252–1258 (2006)
doi:10.1038/sj.embor.7400823
AOP Published online: 3 November 2006
The UBL domain of PLIC-1 regulates aggresome formation
Renu Heir1, Celine Ablasou2, Emilie Dumontier1, Meghan Elliott1, Christine Fagotto-Kaufmann1 & Fiona K Bedford1
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1 Department of Anatomy and Cell Biology, McGill University, 3640 University Street, Montreal, Quebec H3A2B2, Canada
2 Laboratoire d'Immunologie Equipe d'Accueil 2686, Faculte de Medecine, Pole Recherche, 1 Place de Verdun, 59045 Lille, France
To whom correspondence should be addressed
Fiona K Bedford Tel: +1 514 398 1426; Fax: +1 514 398 5047; E-mail: fiona.bedford@mcgill.ca
Received 4 May 2005; Accepted 4 September 2006; Published online 3 November 2006.
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Abstract
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 UBL 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.
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