MEF/ELF4 transactivation by E2F1 is inhibited by p53.
MEF/ELF4 transactivation by E2F1 is inhibited by p53.
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DOI：
10.1093/nar/gkq762
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发表时间：
2011-01
影响因子：
14.9
通讯作者：
Kai H
中科院分区：
文献类型：
--
作者：
Taura M;Suico MA;Fukuda R;Koga T;Shuto T;Sato T;Morino-Koga S;Okada S;Kai H
髓样 elf-1 样因子 (MEF) 或 Elf4 是一种 E-26 (ETS) 相关转录因子，具有强转录活性，通过影响肿瘤抑制因子 p53 来影响细胞衰老。 MEF 通过转录激活 MDM2 下调 p53 表达并抑制 p53 介导的细胞衰老。然而，p53 是否相互对抗 MEF 仍有待探索。在这里，我们证明 MEF 在人类细胞和小鼠组织中受到 p53 的调节。 MEF 表达和启动子活性被 p53 抑制。虽然我们发现 MEF 启动子不包含 p53 响应元件，但有趣的是，它包含 E2F 共有位点。随后，我们确定E2F1特异性结合MEF启动子并反式激活MEF。然而，E2F1 DNA 结合和 MEF 启动子的反式激活通过 p53 和 E2F1 之间的关联而被 p53 抑制。此外，我们发现阿霉素诱导的衰老细胞中p53的激活增加了E2F1和p53的相互作用，减少了E2F1向MEF启动子的募集并减少了MEF的表达。这些观察结果表明，p53 通过与 E2F1（MEF 的一种新型转录激活剂）结合并抑制其结合活性来下调 MEF。结合之前的发现，我们目前的结果表明 p53 和 MEF 之间存在负调控机制。
Myeloid elf-1-like factor (MEF) or Elf4 is an E-twenty-six (ETS)-related transcription factor with strong transcriptional activity that influences cellular senescence by affecting tumor suppressor p53. MEF downregulates p53 expression and inhibits p53-mediated cellular senescence by transcriptionally activating MDM2. However, whether p53 reciprocally opposes MEF remains unex-plored. Here, we show that MEF is modulated by p53 in human cells and mice tissues. MEF expression and promoter activity were suppressed by p53. While we found that MEF promoter does not contain p53 response elements, intriguingly, it contains E2F consensus sites. Subsequently, we determined that E2F1 specifically binds to MEF promoter and transactivates MEF. Nevertheless, E2F1 DNA binding and transactivation of MEF promoter was inhibited by p53 through the association between p53 and E2F1. Furthermore, we showed that activation of p53 in doxorubicin-induced senescent cells increased E2F1 and p53 interaction, diminished E2F1 recruitment to MEF promoter and reduced MEF expression. These observations suggest that p53 downregulates MEF by associating with and inhibiting the binding activity of E2F1, a novel transcriptional activator of MEF. Together with previous findings, our present results indicate that a negative regulatory mechanism exists between p53 and MEF.
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影响因子：
23.9
作者：
Liu Y;Elf SE;Miyata Y;Sashida G;Liu Y;Huang G;Di Giandomenico S;Lee JM;Deblasio A;Menendez S;Antipin J;Reva B;Koff A;Nimer SD
通讯作者：
Nimer SD
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
5.3
作者：
Liu, Y;Hedvat, CV;Nimer, SD
通讯作者：
Nimer, SD
影响因子：
7.5
作者：
Iaquinta, Phillip J.;Lees, Jacqueline A.
通讯作者：
Lees, Jacqueline A.
影响因子：
64.5
作者：
Field, SJ;Tsai, FY;Greenberg, ME
通讯作者：
Greenberg, ME