Stat1 mediates an auto-regulation of hsp90beta gene in heat shock response.
We have reported earlier that a heat shock element in the first intron of human hsp90beta gene (iHSE) acts as an intronic enhancer to bind the heat shock factor (HSF1) and activates hsp90beta gene under heat shock. Here, we show that, in addition to the HSF1, Stat1 phosphorylation is indispensable in the event. We show that Jak2, a Janus kinase specifically associated with the beta subunit of IFNgamma receptor, and PKCepsilon an isoform of the atypical PKC family, are the two dominant kinases responsible for the heat shock induced phosphorylation on Y701 and S727 of Stat1. However, the activation of these kinases under heat shock requires the association of chaperone proteins of the Hsp90 family, in particular, the Hsp90beta under heat shock. Furthermore, Brg1, an ATPase subunit of the SWI/SNF chromatin remodeling complex is likely recruited by HSF1 and Stat1 at the iHSE under heat shock. Brg1 further confers an open chromatin conformation at the promoter region that is pivotal to the heat shock induced fully activation of the hsp90beta gene in Jurkat cells. This is a novel example of how multiple activation steps occur under heat shock, first on the kinases and then the Stat1 and the SWI/SNF chromatin remodeling complex that follows to conduct an auto-regulation based fully activation of the gene.
Cheng
Mo-bin
MB
National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Zhang
Yi
Y
Zhong
Xin
X
Sutter
Benjamin
B
Cao
Chun-yu
CY
Chen
Xue-song
XS
Cheng
Xiao-kuan
XK
Zhang
Ye
Y
Xiao
Lei
L
Shen
Yu-fei
YF
D016227:Benzoquinones / Q000494:pharmacology; D004265:DNA Helicases / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics*; D018869:Heat-Shock Response / Q000235:genetics*; D006706:Homeostasis; D006801:Humans; D007438:Introns; D053614:Janus Kinase 2 / Q000378:metabolism; D019169:Jurkat Cells; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; C493165:HSP90AB1 protein, human; D047029:Lactams, Macrocyclic; D009687:Nuclear Proteins; D050794:STAT1 Transcription Factor; D014157:Transcription Factors; D053614:Janus Kinase 2; D051744:Protein Kinase C-epsilon; C084108:SMARCA4 protein, human; D004265:DNA Helicases; C001277:geldanamycin