The activity of hsp90α promoter is regulated by NF-κB transcription factors

Heat-shock proteins ( HSP) 90 exert a relevant role in the survival and response to therapy of many neoplastic cell types. Here, we show that the promoter of hsp90 alpha gene, that encodes the inducible form of HSP90, is regulated by nuclear factor-kappa B (NF-kappa B) activity. Indeed, we found that NF-kappa B factors bound to one of the two putative consensus sequences present in the hsp90 alpha-flanking region; mutation of such motif hampered the phorbol-myristate-13-acetate-stimulated expression of a luciferase reporter gene under the control of the hsp90a promoter. Furthermore, the downmodulation of NF-kappa B ( p65) levels by a specific small interfering ( si) RNA resulted in reducing the levels of endogenous HSP90 alpha protein. These findings disclose a previously unrecognized mechanism that contributes to connect NF-kappa B factors and HSPs in cell defence machinery.