Co-chaperone CHIP promotes aggregation of ataxin-1

Cited 49 time in scopus
Metadata Downloads
Co-chaperone CHIP promotes aggregation of ataxin-1
Jung Young Choi; J H Ryu; H S Kim; Sung Goo ParkKwang-Hee BaeSunghyun Kang; P K Myung; S Cho; Byoung Chul Park; Do Hee Lee
Bibliographic Citation
Molecular and Cellular Neuroscience, vol. 34, no. 1, pp. 69-79
Publication Year
Recent studies demonstrated that co-chaperone/E3 ligase CHIP (C-terminus of hsp70-interacting protein) mediates the ubiquitylation and suppresses the aggregation of polyglutamine (polyQ) proteins, such as huntingtin or ataxin-3. In this study, we investigated the effects of CHIP on the degradation of another polyQ protein ataxin-1. Interestingly CHIP associates not only with the polyQ-expanded ataxin-1 but also with the normal ataxin-1. Moreover, by enhancing ataxin-1 ubiquitylation, CHIP over-expression leads to a reduction in the solubility of ataxin-1 and thus increases the aggregate formation, especially that of polyQ-expanded ataxin-1. Domain analysis revealed that the TPR domain is required for the promotion of aggregation. By contrast, other co-chaperones or E3 ligases, such as BAG-1 or parkin, did not show similar effects on the aggregation of ataxin-1. Importantly, the effect of CHIP is impaired by the mutation of Ser776 of ataxin-1 whose phosphorylation is crucial for ataxin-1 aggregation. Our findings suggest that the role of CHIP in aggregation of polyQ proteins greatly varies depending on the context of full-length polyQ proteins.
Appears in Collections:
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
Critical Diseases Diagnostics Convergence Research Center > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.

Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.