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PKC‐alpha Potentially Mediates Transcription of the Inducible HSP70 via AP‐1
Author(s) -
Mestril Ruben,
Mirza Osman
Publication year - 2009
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.23.1_supplement.953.17
Subject(s) - hsp70 , luciferase , transcription factor , transcription (linguistics) , microbiology and biotechnology , promoter , biology , protein kinase c , transfection , reporter gene , heat shock protein , chemistry , signal transduction , gene , gene expression , genetics , linguistics , philosophy
Prior research has established the involvement of both PKC and HSP proteins in conferring cardioprotection. The interaction between these two families has implicated that PKC‐α mediates induction of Hsp70 and subsequent protection against simulated ischemia‐reperfusion in neonatal rat ventricular myocytes. Surprisingly, Hsp70 induction by PKC‐α was found to be both highly specific and independent of the conventional heat shock transcription factor HSF‐1. In an effort to elucidate the underlying mechanism, we linked a luciferase reporter gene to chimeric constructs of the 5' promoter region of the rat Hsp70. Constructs were transfected into myogenic H9c2 cells followed by adenoviral mediated overexpression of PKC‐α. Since regulation by PKC‐α was found to be independent of HSF‐1, the significance of other transcription factors exerting their action on the promoter region of Hsp70 was investigated. Our results show that induction of the Hsp70 promoter by PKC‐α is preserved within the first 175 base pairs from the start of transcription. The sequence of the Hsp70 promoter in this segment contains at least two canonic Ap‐1 signaling elements. Further restrictions of the ‐175 bp promoter region may reveal the possible role of these Ap‐1 sites in the transcriptional activation of Hsp70 by PKC‐α. Insertion of Ap‐1 signals upstream of a basal promoter‐luciferase construct could further confirm their significance.