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

Neurosci Bull. 2010 Apr;26(2):153-62. doi: 10.1007/s12264-010-1118-6.


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. 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.

翻译后修饰能快速、 有效且可逆地调节蛋白的稳定性、 分布位置、 功能及其与其它分子之间的相互作用。 翻译后修饰主要包括氨基酸残基的SUMO 化、 磷酸化、 棕榈化以及乙酰化等。 这些复杂的生化修饰能严格、 规范地调节各种细胞过程。 亨廷顿蛋白(Htt)的几种翻译后修饰方式已见报道。 这些翻译后修饰会影响Htt的代谢、 Htt与其它蛋白质的相互作用以及Htt的细胞毒性。 突变Htt的剪切、 清除以及与其它细胞蛋白质的相互作用是导致亨廷顿病的重要生化事件。 因此, 了解Htt修饰的信号转导及其意义, 可以帮助我们更好地理解野生型Htt的正常功能和突变Htt的致病机制。

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Humans
  • Huntingtin Protein
  • Huntington Disease / genetics*
  • Huntington Disease / metabolism*
  • Huntington Disease / pathology
  • Models, Biological
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Processing, Post-Translational / physiology*
  • Trinucleotide Repeat Expansion / genetics


  • HTT protein, human
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Nuclear Proteins