| First Author | Aiken CT | Year | 2009 |
| Journal | J Biol Chem | Volume | 284 |
| Issue | 43 | Pages | 29427-36 |
| PubMed ID | 19710014 | Mgi Jnum | J:157814 |
| Mgi Id | MGI:4436997 | Doi | 10.1074/jbc.M109.013193 |
| Citation | Aiken CT, et al. (2009) Phosphorylation of threonine 3: implications for Huntingtin aggregation and neurotoxicity. J Biol Chem 284(43):29427-36 |
| abstractText | Huntingtin (Htt) is a widely expressed protein that causes tissue-specific degeneration when mutated to contain an expanded polyglutamine (poly(Q)) domain. Although Htt is large, 350 kDa, the appearance of amino-terminal fragments of Htt in extracts of postmortem brain tissue from patients with Huntington disease (HD), and the fact that an amino-terminal fragment, Htt exon 1 protein (Httex1p), is sufficient to cause disease in models of HD, points to the importance of the amino-terminal region of Htt in the disease process. The first exon of Htt encodes 17 amino acids followed by a poly(Q) repeat of variable length and culminating with a proline-rich domain of 50 amino acids. Because modifications to this fragment have the potential to directly affect pathogenesis in several ways, we have surveyed this fragment for potential post-translational modifications that might affect Htt behavior and detected several modifications of Httex1p. Here we report that the most prevalent modifications of Httex1p are NH(2)-terminal acetylation and phosphorylation of threonine 3 (pThr-3). We demonstrate that pThr-3 occurs on full-length Htt in vivo, and that this modification affects the aggregation and pathogenic properties of Htt. Thus, therapeutic strategies that modulate these events could in turn affect Htt pathogenesis. |
