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Huntingtin interacting protein HYPK is a negative regulator of heat shock response and is downregulated in models of Huntington's Disease.

Abstract：

:Huntingtin interacting protein HYPK (Huntingtin Yeast Partner K) is an intrinsically unstructured protein having chaperone-like activity and can suppress mutant huntingtin aggregates and toxicity in cell model of Huntington's Disease (HD). Heat shock response is an adaptive mechanism of cells characterized by upregulation of heat shock proteins by heat-induced activation of heat shock factor 1 (HSF1). The trans-activation ability of HSF1 is arrested upon restoration of proteostasis. We earlier identified HYPK as a heat-inducible protein and transcriptional target of HSF1. Here we show that HYPK can act as negative regulator of heat shock response by repressing transcriptional activity of HSF1. As part of its role as a repressor of heat shock response, HYPK can also inhibit HSF1-dependent trans-activation of its own promoter. HYPK is downregulated in cell and animal model of HD. We further show that transcriptional downregulation of HYPK in HD cell model is a consequence of reduced occupancy of HSF1 in HYPK promoter. Moreover, presence of mutant huntingtin inhibits effective induction of HYPK in response to heat shock. Taken together, our findings reveal that HYPK can suppress heat shock response via an autoregulatory loop and downregulation of HYPK in HD is caused by impaired transcriptional activity of HSF1 in presence of mutant huntingtin.

journal_name

Exp Cell Res

journal_title

Experimental cell research

authors

Das S,Bhattacharyya NP

doi

10.1016/j.yexcr.2016.03.021

subject

Has Abstract

pub_date

2016-05-01 00:00:00

pages

107-117

issue

2

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(16)30061-1

journal_volume

343

pub_type

杂志文章

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