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

Abstract

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 hsp90a gene, that encodes the inducible form of HSP90, is regulated by nuclear factor-jB (NF-jB) activity. Indeed, we found that NF-jB factors bound to one of the two putative consensus sequences present in the hsp90a-flanking region; mutation of such motif hampered the phorbol-myristate-13-acetatestimulated expression of a luciferase reporter gene under the control of the hsp90a promoter. Furthermore, the downmodulation of NF-jB (p65) levels by a specific small interfering (si) RNA resulted in reducing the levels of endogenous HSP90a protein. These findings disclose a previously unrecognized mechanism that contributes to connect NF-jB factors and HSPs in cell defence machinery.

Heat shock protein 90 regulates IκB kinase complex and NF-κB activation in angiotensin II-induced cardiac cell hypertrophy

“…Moreover, GA decreases the IKKα/β stability and blocks the interaction of HSP90 with IKK complex in response to angiotensin II. Although several examples of evidence on the roles of HSP90 in the NF-κB pathway have been reported recently (Arthur et al, 2007;Ammirante et al, 2008), the crosstalk between HSP90 and the NF-κB signaling cascade in cardiac hypertrophy induced by angiotensin II remains unclear. In the present work, accompanied by cellular hypertrophic events, angiotensin II activated the NF-κB signaling cascade such as IKKs activation and NF-κB nuclear translocation, which finding is consistent with previous studies.…”

Hsp70 and cardiac surgery: molecular chaperone and inflammatory regulator with compartmentalized effects

“…Interestingly, intracellular signaling activity of NF-κB induced upregulation of HSF1 and Hsp70 (Hamilton et al 2004), possibly due to NF-κB signaling-associated oxidative stress (Adrie and Pinsky 2000). Heat shock protein-mediated negative feedback on NF-κB activity could thereby represent an important immunoregulatory pathway (Ammirante et al 2008). The intracellular anti-inflammatory effects of Hsp70 may involve inhibition of IκB kinase (IKK) activity by binding to its regulatory IKKγ subunit (Ran et al 2004).…”

Effects of Coenzyme Q10 on Rat Liver Cells under Conditions of Metabolic Stress

“…The middle peak corresponds to hepatocytes responding by proliferation to CoQ10 supplementation during starvation. I: starvation 5 days; II: starvation, 5 days+CoQ10, 10 mg; III: starvation, 5 days+CoQ10, 100 mg; IV: starvation, 5 days+100% ration, 5 days; V: starvation 5, days+100% ration 5 days+CoQ10, 10 mg; VI: starvation, 5 days+100% ration, 5 days+CoQ10, 100 mg. I II III IV V VI totic signals, cell responses to nutrients, and ATP level [2,10]. Hsp90 regulates expression of certain proteins promoting degradation of NF-κB-inducible kinase [3].…”