The activity of hsp90α promoter is regulated by NF-κB transcription factors
The activity of hsp90α promoter is regulated by NF-κB transcription factors
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DOI：
10.1038/sj.onc.1210716
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发表时间：
2008-02-14
期刊：
影响因子：
8
通讯作者：
Turco, M. C.
中科院分区：
文献类型：
--
作者：
Ammirante, M.;Rosati, A.;Turco, M. C.
热休克蛋白(HSP)90在多种肿瘤细胞的存活和治疗反应中发挥重要作用。在这里，我们证明了编码HSP90诱导形式的HSP90α基因的启动子受核因子-kappa B(NF-kappa B)活性的调节。事实上，我们发现NF-kappa B因子与HSP90α侧翼区域存在的两个假定一致序列中的一个结合；这种基序的突变阻碍了在hsp90a启动子的控制下由佛波醇-肉豆蔻-13-乙酸酯刺激的荧光素酶报告基因的表达。此外，特定的小干扰(Si)RNA下调了核因子-kappa B(P65)水平，导致内源性HSP90α蛋白水平降低。这些发现揭示了一种以前未知的机制，该机制有助于在细胞防御机制中连接核因子-kappa B因子和热休克蛋白。
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.