Synergistic cooperation of MDM2 and E2F1 contributes to TAp73 transcriptional activity
Synergistic cooperation of MDM2 and E2F1 contributes to TAp73 transcriptional activity
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MDM2 和 E2F1 的协同合作有助于 TAp73 转录活性
DOI：
10.1016/j.bbrc.2014.05.026
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发表时间：
2014-07-04
影响因子：
3.1
通讯作者：
Wu, Shourong
中科院分区：
文献类型：
--
作者：
Kasim, Vivi;Huang, Can;Wu, Shourong
TAp 73是p53的结构同源物，在肿瘤发生中起重要作用。E2 F1已被报道为TAp 73的转录调控因子，但其具体机制仍有待阐明。在这里，我们报道了MDM 2沉默显著降低了TAp 73启动子的活性和内源性TAp 73表达水平;而MDM 2过表达上调了它们。我们进一步揭示了TAp 73转录活性的调节作为MDM 2和E2 F1的协同效应而发生，最有可能是通过它们在细胞核中的物理相互作用。此外，我们还建议MDM 2可能参与DNA损伤诱导的TAp 73转录活性。最后，我们阐明了MDM 2沉默降低了结肠癌细胞的增殖率，而与p53状态无关。我们的数据显示MDM 2和E2 F1对TAp 73转录活性的协同作用，表明TAp 73的新调控途径。(C)2014爱思唯尔公司All rights reserved.
TAp73, a structural homologue of p53, plays an important role in tumnorigenesis. E2F1 had been reported as a transcriptional regulator of TAp73, however, the detailed mechanism remains to be elucidated. Here we reported that MDM2-silencing reduced the activities of the TAp73 promoters and the endogenous TAp73 expression level significantly; while MDM2 overexpression upregulated them. We further revealed that the regulation of TAp73 transcriptional activity occurs as a synergistic effect of MDM2 and E2F1, most probably through their physical interaction in the nuclei. Furthermore, we also suggested that MDM2 might be involved in DNA damage-induced TAp73 transcriptional activity. Finally, we elucidated that MDM2-silencing reduced the proliferation rate of colon carcinoma cells regardless of the p53 status. Our data show a synergistic effect of MDM2 and E2F1 on TAp73 transcriptional activity, suggesting a novel regulation pathway of TAp73. (C) 2014 Elsevier Inc. All rights reserved.