The UBL domain of PLIC-1 regulates aggresome formation.
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(DeltaUBL) 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.[1]References
- The UBL domain of PLIC-1 regulates aggresome formation. Heir, R., Ablasou, C., Dumontier, E., Elliott, M., Fagotto-Kaufmann, C., Bedford, F.K. EMBO Rep. (2006) [Pubmed]
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