Ubiquilin interacts and enhances the degradation of expanded-polyglutamine proteins.
Previously, we showed that overexpression of ubiquilin reduces protein aggregates and toxicity of expanded polyglutamine proteins. Here, we investigated the mechanism of ubiquilin's protective effect. Immunofluorescence microscopy and immunoprecipitation studies indicated that ubiquilin colocalized and coimmunoprecipitated more with GFP-huntingtin-exon-1-fusion proteins containing a 74-polyglutamine tract than with GFP-huntingtin-fusion proteins containing a 28-polyglutamine tract or with GFP protein alone. Furthermore, overexpression of ubiquilin selectively enhanced the turnover of the expanded GFP-huntingtin-fusion protein. These results suggest that elevating ubiquilin levels could aid in the selective disposal of potentially toxic expanded polyglutamine proteins that are thought to cause several human diseases.
Wang
Hongmin
H
Institute for Neurodegenerative Diseases, Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, MD 21201, USA.
Monteiro
Mervyn J
MJ
D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D006801:Humans; D010455:Peptides / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D010455:Peptides; C107792:UBQLN1 protein, human; C097188:polyglutamine