Steroid receptor coactivator-1 and its family members differentially regulate transactivation by the tumor suppressor protein p53
Steroid receptor coactivator-1 and its family members differentially regulate transactivation by the tumor suppressor protein p53
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DOI：
10.1210/me.13.11.1924
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发表时间：
1999-11-01
影响因子：
--
通讯作者：
Lee, JW
中科院分区：
文献类型：
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作者：
Lee, SK;Kim, HJ;Lee, JW
肿瘤抑制蛋白P53通过其作为序列特异性DNA结合转录因子的功能发挥其细胞周期调节作用。在这里，我们证明了P53与类固醇受体共激活因子-1(SRC-1)及其家族成员p/CIP(p300/CBP相互作用蛋白)、xSRC-3和AIB1(在乳腺癌中扩增)的特定亚区物理上的相互作用，酵母和哺乳动物双杂交试验以及谷胱甘肽S转移酶下拉试验证明了这一点。有趣的是，与SRC-1或p/CIP表达载体共转染HeLa细胞可增强P53介导的反式激活，而AIB1和xSRC-3则被抑制。然而，所有这些SRC-1成员都类似地刺激由核受体和AP-1介导的反式激活，如前所述。这些结果表明，SRC-1及其家族成员在体内可能对P53的反式激活有不同的调节作用。
The tumor suppressor protein p53 exerts its cell cycle-regulatory effects through its ability to function as a sequence-specific DNA-binding transcription factor. Herein, we show that p53 physically interacts with specific subregions of steroid receptor coactivator-1 (SRC-1) and its family members, p/CIP (p300/CBP interacting protein), xSRC-3, and AIB1 (amplified in breast cancer), originally isolated as transcription coactivators of nuclear receptors, as demonstrated by the yeast and mammalian two-hybrid tests as well as glutathione S-transferase pull-down assays. Interestingly, cotransfection of HeLa cells with SRC-1- or p/CIP expression vector potentiated the p53-mediated transactivation, whereas AIB1 and xSRC-3 were repressive. All of these SRC-1 members, however, similarly stimulated transactivation mediated by nuclear receptors and AP-1, as previously described. These results suggest that SRC-1 and its family members may differentially modulate the p53 transactivation in vivo.