Tài liệu Báo cáo khoa học: The heat shock factor family and adaptation to proteotoxic stress pdf

MINIREVIEW

The heat shock factor family and adaptation to

proteotoxic stress

Mitsuaki Fujimoto and Akira Nakai

Yamaguchi University School of Medicine, Ube, Japan

Introduction

All living organisms respond to elevated temperatures

by producing a set of highly conserved proteins,

known as heat shock proteins (HSP) [1]. This response

is called the heat shock response, and is a universal

mechanism of protection against proteotoxic stress,

including heat shock and oxidative stress. In Escheri￾chia coli, heat shock genes are under the control of a

specific transcription factor, r32, which directs the

core RNA polymerase to promoters [2]. In eukaryotes,

the heat shock response is regulated mainly at the level

of transcription by heat shock factors (HSFs) [3]. Heat

shock genes, such as HSP110, HSP90, HSP70, HSP40

and HSP27, contain heat shock elements (HSEs) com￾posed of at least three inverted repeats of the highly

conserved consensus sequence nGAAn in the proximal

promoter region [4]. Here we call them ‘classical heat

shock genes’, which encode major HSPs or molecular

chaperones. Heat shock triggers the conversion of an

HSF1 monomer in a metazoan species that is nega￾tively regulated by HSPs into a trimer that binds to

Keywords

evolution; heat shock; protein homeostasis;

protein-misfolding disorder; transcription

factor; vertebrate

Correspondence

Akira Nakai, Department of Biochemistry

and Molecular Biology, Yamaguchi

University School of Medicine, Minami￾Kogushi 1-1-1, Ube 755-8505, Japan

Fax: 81 836 22 2315

Tel: 81 836 22 2214

E-mail: [email protected]

(Received 10 May 2010, revised 7 July

2010, accepted 23 July 2010)

doi:10.1111/j.1742-4658.2010.07827.x

The heat shock response was originally characterized as the induction of a

set of major heat shock proteins encoded by heat shock genes. Because

heat shock proteins act as molecular chaperones that facilitate protein fold￾ing and suppress protein aggregation, this response plays a major role in

maintaining protein homeostasis. The heat shock response is regulated

mainly at the level of transcription by heat shock factors (HSFs) in eukary￾otes. HSF1 is a master regulator of the heat shock genes in mammalian

cells, as is HSF3 in avian cells. HSFs play a significant role in suppressing

protein misfolding in cells and in ameliorating the progression of Caenor￾habditis elegans, Drosophila and mouse models of protein-misfolding

disorders, by inducing the expression of heat shock genes. Recently, numer￾ous HSF target genes were identified, such as the classical heat shock genes

and other heat-inducible genes, called nonclassical heat shock genes in this

study. Importance of the expression of the nonclassical heat shock genes

was evidenced by the fact that mouse HSF3 and chicken HSF1 play a sub￾stantial role in the protection of cells from heat shock without inducing

classical heat shock genes. Furthermore, HSF2 and HSF4, as well as

HSF1, shown to have roles in development, were also revealed to be neces￾sary for the expression of certain nonclassical heat shock genes. Thus, the

heat shock response regulated by the HSF family should consist of the

induction of classical as well as of nonclassical heat shock genes, both of

which might be required to maintain protein homeostasis.

Abbreviations

BRG1, brahma-related gene 1; DAF-16, abnormal dauer formation 16; HR, hydrophobic heptad repeat; HSE, heat shock element; HSF, heat

shock factor; HSP, heat shock protein; MEF, mouse embryonic fibroblast; polyQ, polyglutamine.

4112 FEBS Journal 277 (2010) 4112–4125 ª 2010 The Authors Journal compilation ª 2010 FEBS