The activity of hsp90 alpha promoter is regulated by NF-kappa B 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 hsp90alpha gene, that encodes the inducible form of HSP90, is regulated by nuclear factor-kappaB (NF-kappaB) activity. Indeed, we found that NF-kappaB factors bound to one of the two putative consensus sequences present in the hsp90alpha-flanking region; mutation of such motif hampered the phorbol-myristate-13-acetate-stimulated expression of a luciferase reporter gene under the control of the hsp90alpha promoter. Furthermore, the downmodulation of NF-kappaB (p65) levels by a specific small interfering (si) RNA resulted in reducing the levels of endogenous HSP90alpha protein. These findings disclose a previously unrecognized mechanism that contributes to connect NF-kappaB factors and HSPs in cell defence machinery.
Ammirante
M
M
Department of Pharmaceutical Sciences (DiFarma), University of Salerno, Fisciano (SA), Italy.
Rosati
A
A
Gentilella
A
A
Festa
M
M
Petrella
A
A
Marzullo
L
L
Pascale
M
M
Belisario
M A
MA
Leone
A
A
Turco
M C
MC
D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D017930:Genes, Reporter; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000502:physiology; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*
D018841:HSP90 Heat-Shock Proteins; C493165:HSP90AB1 protein, human; D051996:Transcription Factor RelA