NEGATIVE REGULATION OF THE HEAT-SHOCK TRANSCRIPTIONAL RESPONSE BY HSBP1

Citation
Sh. Satyal et al., NEGATIVE REGULATION OF THE HEAT-SHOCK TRANSCRIPTIONAL RESPONSE BY HSBP1, Genes & development, 12(13), 1998, pp. 1962-1974
Citations number
75
Categorie Soggetti
Developmental Biology","Genetics & Heredity
Journal title
ISSN journal
08909369
Volume
12
Issue
13
Year of publication
1998
Pages
1962 - 1974
Database
ISI
SICI code
0890-9369(1998)12:13<1962:NROTHT>2.0.ZU;2-R
Abstract
In response to stress, heat shock factor 1 (HSP1) acquires rapid DNA b inding and transient transcriptional activity while undergoing conform ational transition from an inert non-DNA-binding monomer to active fun ctional trimers. Attenuation of the inducible transcriptional response occurs during heat shock or upon recovery at non-stress conditions an d involves dissociation of the HSF1 trimer and loss of activity. We ha ve used the hydrophobic repeats of the HSF1 trimerization domain in th e yeast two-hybrid protein interaction assay to identify heat shock fa ctor binding protein 1 (HSBP1), a novel, conserved, 76-amino-acid prot ein that contains two extended arrays of hydrophobic repeats that inte ract with the HSF1 heptad repeats. HSBP1 is nuclear-localized and inte racts in vivo with the active trimeric state of HSF1 that appears duri ng heat shack. During attenuation of HSF1 to the inert monomer, HSBP1 associates with Hsp70. HSBP1 negatively affects HSF1 DNA-binding activ ity, and overexpression of HSBP1 in mammalian cells represses the tran sactivation activity of HSF1. To establish a biological role for HSBP1 , the homologous Caenorhabditis elegans protein was overexpressed in b ody wall muscle cells and was shown to block activation of the heat sh ock response from a heat shock promoter-reporter construct. Alteration in the level of HSBP1 expression in C. elegans has severe effects on survival of the animals after thermal and chemical stress, consistent with a role for HSBP1 as a negative regulator of the heat shock respon se.