Phosphorylation of huntingtin at residue T3 is decreased in Huntington’s disease and modulates mutant huntingtin protein conformation

• DOI: 10.1073/pnas.1705372114
• Publication Date: 2017-11-21T17:20:44Z
• Authors: Cristina Cariulo; Lucia Azzollini; Margherita Verani; Paola Martufi; Roberto Boggio; Anass Chiki; Sean M. Deguire; Marta Cherubini; Silvia Gines; J. Lawrence Marsh; Paola Conforti; Elena Cattaneo; Iolanda Santimone; Ferdinando Squitieri; Hilal A. Lashuel; Lara Petricca; Andrea Caricasole
• Keywords: Huntingtin Protein; Polyglutamine tract; Mutant protein

Significance The findings in this manuscript report on the identification of a posttranslational modification huntingtin protein (phosphorylation residue T3 N17 region protein), which can revert conformational effects Huntington’s disease (HD) mutation itself and inhibit its aggregation properties vitro. Using first ultrasensitive immunoassay for protein, we demonstrate that pT3 levels are decreased mutant preclinical models as well clinically relevant samples from HD patients. These high significance to biology, provide insights into mechanisms pathogenesis, open new opportunities development therapeutics diagnostics disease.