Lysine Acetylation in Huntingtin and Its Role in the Pathogenesis of Huntington's Disease

摘要

In this study, the MS-based protocols allowed for identification of lysine acetylation in Htt. Lysine acetylation at the N-terminal of Htt (K9) may affect toxicity by controlling Htt trafficking. Acetylated lysine at K178 may affect Htt cleavage by changing other post-translational modifications such as phosphorylation which has been proved to have an effect on Htt stability(Y173 is a highly predicted phosphorylation site.). Moreover, a relative quantification of Htt acetylation comparing normal and disease forms of Htt is underway. The results combined with biological evidences should give us more insight on how these modifications affect the function and regulation of Htt, particularly their role in altering proteolysis and the production of cytotoxic N-terminal fragments.