Volume 26, Issue. 2, April, 2010


The role of post-translational modifications of huntingtin in the pathogenesis of Huntington’s disease

 Yan WANG, Fang LIN, Zheng-Hong QIN  


Department of Pharmacology, Laboratory of Aging and Nervous Diseases (SZS0703), Soochow University School of Medicine, Suzhou 215123, China

Abstract 

Post-translational modifications are rapid, effective and reversible ways to regulate protein stability, localization, function, and their interactions with other molecules. Post-translational modifications usually occur as chemical modifications at amino acid residues, including SUMOylation, phosphorylation, palmitoylation, acetylation, etc. These complex biochemical modifications tightly regulate and control a variety of cellular processes. Several forms of post-translational modifications of huntingtin (Htt) have been described. These modifications affect Htt metabolism, protein-protein interactions and cellular toxicity. Cleavage and clearance of mutant Htt, and the interactions between mutant Htt and other cellular proteins are important biochemical events leading to Huntington’s disease (HD). Therefore, identifying signaling pathways of Htt modification and evaluating the significance of Htt modifications would lead to a better understanding of the normal function of wild-type Htt and the pathogenic mechanisms of mutant Htt.

Keywords

Huntington’s disease; huntingtin; modification; SUMOylation; phosphorylation; palmitoylation; acetylation

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