| First Author | Choudhury KR | Year | 2015 |
| Journal | Biochem Biophys Res Commun | Volume | 456 |
| Issue | 1 | Pages | 66-73 |
| PubMed ID | 25446099 | Mgi Jnum | J:220288 |
| Mgi Id | MGI:5634072 | Doi | 10.1016/j.bbrc.2014.11.035 |
| Citation | Choudhury KR, et al. (2015) Chaperone protein HYPK interacts with the first 17 amino acid region of Huntingtin and modulates mutant HTT-mediated aggregation and cytotoxicity. Biochem Biophys Res Commun 456(1):66-73 |
| abstractText | Huntington's disease is a polyglutamine expansion disorder, characterized by mutant HTT-mediated aggregate formation and cytotoxicity. Many reports suggests roles of N-terminal 17 amino acid domain of HTT (HTT-N17) towards subcellular localization, aggregate formation and subsequent pathogenicity induced by N-terminal HTT harboring polyQ stretch in pathogenic range. HYPK is a HTT-interacting chaperone which can reduce N-terminal mutant HTT-mediated aggregate formation and cytotoxicity in neuronal cell lines. However, how HYPK interacts with N-terminal fragment of HTT remained unknown. Here we report that specific interaction of HYPK with HTT-N17 is crucial for the chaperone activity of HYPK. Deletion of HTT-N17 leads to formation of tinier, SDS-soluble nuclear aggregates formed by N-terminal mutant HTT. The increased cytotoxicity imparted by these tiny aggregates might be contributed due to loss of interaction with HYPK. |
