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NF‐κB and HSF‐1 coordinated transcriptional regulation of the Hsp70.3 promoter
Author(s) -
Helsley Robert Nathaniel,
Tranter Michael,
McGuinness Myc,
Haar Lauren,
Paulding Waltke R.,
Jones W. Keith
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1085.13
Subject(s) - hsp70 , transcriptional regulation , nf κb , promoter , microbiology and biotechnology , chemistry , biology , transcription factor , gene , heat shock protein , gene expression , biochemistry , signal transduction
Work from our lab and others has previously shown that late IPC cardioprotection is dependent on transcriptional activation of HSF‐1 and NF‐κB‐dependent gene networks and subsequent expression of the heat shock protein 70.3 (Hsp70.3). The goal of this work is to identify the mechanisms of transcriptional control acting on the gene promoter of stress‐inducible Hsp70 (Hsp70.3 and the very homologous Hsp70.1). Results Sequence analysis of the Hsp70.3 promoter region suggests potential binding sites for HSF‐1 and NF‐κB, among other factors. We hypothesize that HSF‐1 and NF‐κB coordinately regulate transcriptional control of the Hsp70.3 promoter . Results using transcription factor knockout Murine Embyronic Fibroblasts ( hsf1 −/− , p65 −/− , and p50 −/− ) and Hsp70.3 luciferase reporters in response to heat shock treatment show that HSF‐1 and the p65 subunit of NF‐κB are both necessary for Hsp70.3 expression. Interestingly, knockout of the p50 NF‐κB subunit does not appear to reduce Hsp70.3 expression. Discussion This work is the first to conclusively show that NF‐κB directly controls transcriptional expression of the Hsp70.3 gene. Our results also suggest an NF‐κB and HSF‐1 coordinated regulation of Hsp70.3 expression. This work was supported by an ASPET Dalton/Zannoni Fellowship (RNH) and NIH RO1 HL091478 (WKJ).