p300/CBP-dependent and -independent transcriptional interference between NF-κB RelA and p53
p300/CBP-dependent and -independent transcriptional interference between NF-κB RelA and p53
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DOI：
10.1006/bbrc.2000.2786
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发表时间：
2000-06-07
影响因子：
3.1
通讯作者：
Yamamoto, K
中科院分区：
文献类型：
--
作者：
Ikeda, A;Sun, XG;Yamamoto, K
p53 和 NF-kappa B RelA 被各种基因毒性剂激活，并相互抑制彼此激活转录的能力，最有可能是通过竞争转录共激活因子（如 CBP 或 p300）。然而，我们发现，CBP/p300 过表达并不能完全恢复 RelA 对 p53 转录活性的抑制，并且 p53 突变体尽管能够结合 CBP/p300，但不能抑制 RelA 活性。在本研究中，我们进一步证明这两种转录因子在体内和体外直接相互作用。因此，这些结果表明p53和RelA之间的交叉转录干扰部分是由这两个转录因子之间的直接相互作用引起的，该相互作用由它们的二聚化/四聚化结构域介导，并导致彼此转录活性的抑制。最后，来自 RelA 敲除小鼠的细胞显示出增强的 p53 转录活性，表明这种交叉转录干扰在细胞对基因毒性应激的反应中具有重要的生理意义。 (C) 2000 年学术出版社。
p53 and NF-kappa B RelA are activated by various genotoxic agents and mutually suppress each other's ability to activate transcription, most likely through competition for transcriptional coactivators such as CBP or p300. However, we found that the inhibition by RelA of p53 transcriptional activity is not completely restored by CBP/p300 overexpression and that a p53 mutant can not suppress RelA activity despite of its ability to bind CBP/p300. In the present study, we further present evidence that these two transcriptional factors directly interact both in vivo and in vitro. These results therefore indicate that the cross transcriptional interference between p53 and RelA is partly caused by the direct interaction between these two transcription factors which is mediated by their dimerization/tetramerization domains and results in inhibition of each other's transcriptional activity. Finally, cells derived from RelA knockout mice showed enhanced p53 transcriptional activity, suggesting that this cross transcriptional interference is physiologically important in cellular response to genotoxic stress. (C) 2000 Academic Press.