Chaperone protein HYPK interacts with the first 17 amino acid region of Huntingtin and modulates mutant HTT-mediated aggregation and cytotoxicity

Choudhury, Kamalika Roy and Bhattacharyya, Nitai P (2015) Chaperone protein HYPK interacts with the first 17 amino acid region of Huntingtin and modulates mutant HTT-mediated aggregation and cytotoxicity. In: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 456 (1). pp. 66-73.

PDF bio_bio_res_com_456-1_66_2015.pdf - Published Version Restricted to Registered users only Download (1MB) | Request a copy

Abstract

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. (C) 2014 Elsevier Inc. All rights reserved.

Item Type:	Journal Article
Publication:	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Publisher:	ACADEMIC PRESS INC ELSEVIER SCIENCE
Additional Information:	Copy right for this article belongs to the Department of Atomic Energy, Govt. of India
Keywords:	Huntington's disease; HYPK; HTT-N17; Aggregate; Cytotoxicity
Department/Centre:	Division of Biological Sciences > Centre for Neuroscience
Date Deposited:	04 Mar 2015 12:09
Last Modified:	04 Mar 2015 12:09
URI:	http://eprints.iisc.ac.in/id/eprint/50952

Actions (login required)

View Item