[HTML][HTML] Huntingtin phosphorylation sites mapped by mass spectrometry: modulation of cleavage and toxicity
B Schilling, J Gafni, C Torcassi, X Cong… - Journal of Biological …, 2006 - ASBMB
Huntingtin (Htt) is a large protein of 3144 amino acids, whose function and regulation have
not been well defined. Polyglutamine (polyQ) expansion in the N terminus of Htt causes the
neurodegenerative disorder Huntington disease (HD). The cytotoxicity of mutant Htt is
modulated by proteolytic cleavage with caspases and calpains generating N-terminal polyQ-
containing fragments. We hypothesized that phosphorylation of Htt may modulate cleavage
and cytotoxicity. In the present study, we have mapped the major phosphorylation sites of Htt …
not been well defined. Polyglutamine (polyQ) expansion in the N terminus of Htt causes the
neurodegenerative disorder Huntington disease (HD). The cytotoxicity of mutant Htt is
modulated by proteolytic cleavage with caspases and calpains generating N-terminal polyQ-
containing fragments. We hypothesized that phosphorylation of Htt may modulate cleavage
and cytotoxicity. In the present study, we have mapped the major phosphorylation sites of Htt …