Zinc Finger 280B regulates sGCα1 and p53 in prostate cancer cells.
Zinc Finger 280B regulates sGCα1 and p53 in prostate cancer cells.
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DOI：
10.1371/journal.pone.0078766
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Shemshedini L
中科院分区：
文献类型：
--
作者：
Gao S;Hsieh CL;Zhou J;Shemshedini L
锌指（ZNF） 280B蛋白被发现是sGCα1 shRNA的意外靶点。进一步分析表明，这两种蛋白以另一种方式连接，通过280B上调sgc - α1的表达。敲除和过表达实验表明280B在前列腺癌中具有促生长和促存活的功能。然而，令人惊讶的是，280B的这些促癌功能不是由sGCα1介导的，而是由下调的p53介导的，而sGCα1本身在前列腺癌中具有类似的功能。p53蛋白是280B在前列腺癌中的第二个靶点，但与sGCα1不同，p53蛋白被280B下调。280B诱导p53核输出，导致随后的蛋白酶体降解。由280B调控p53的蛋白是Mdm2，这是一种E3泛素连接酶，通过诱导其核输出来促进p53的降解。我们在这里表明，280B上调Mdm2在前列腺癌细胞中的表达，这种调节是通过Mdm2启动子进行的。为了证明这种相互作用的体内相关性，表达研究表明280B蛋白水平在前列腺癌中上调，而这些水平对应于p53水平的降低。因此，通过增强Mdm2的表达，未知的280B蛋白在前列腺癌中提供了抑制p53的新机制。
The Zinc Finger (ZNF) 280B protein was identified as an unexpected target of an shRNA designed for sGCα1. Further analysis showed that these two proteins are connected in another way, with 280B up-regulation of sGCα1 expression. Knock-down and over-expression experiments showed that 280B serves pro-growth and pro-survival functions in prostate cancer. Surprisingly however, these pro-cancer functions of 280B are not mediated by sGCα1, which itself has similar functions in prostate cancer, but by down-regulated p53. The p53 protein is a second target of 280B in prostate cancer, but unlike sGCα1, p53 is down-regulated by 280B. 280B induces p53 nuclear export, leading to subsequent proteasomal degradation. The protein responsible for p53 regulation by 280B is Mdm2, the E3 ubiquitin ligase that promotes p53 degradation by inducing its nuclear export. We show here that 280B up-regulates expression of Mdm2 in prostate cancer cells, and this regulation is via the Mdm2 promoter. To demonstrate an in vivo relevance to this interaction, expression studies show that 280B protein levels are up-regulated in prostate cancer and these levels correspond to reduced levels of p53. Thus, by enhancing the expression of Mdm2, the uncharacterized 280B protein provides a novel mechanism of p53 suppression in prostate cancer.
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影响因子：
8
作者：
Cai, C.;Chen, S-Y;Shemshedini, L.
通讯作者：
Shemshedini, L.
影响因子：
--
作者：
Cai, Changmeng;Hsieh, Chen-Lin;Shemshedini, Lirim
通讯作者：
Shemshedini, Lirim
影响因子：
3.7
作者：
Huang, Chuanxin;Jia, Yichang;Wang, Yizheng
通讯作者：
Wang, Yizheng
影响因子：
11.2
作者：
Hu R;Peng G;Dai H;Breuer EK;Stemke-Hale K;Li K;Gonzalez-Angulo AM;Mills GB;Lin SY
通讯作者：
Lin SY
影响因子：
5.2
作者：
Cai, Changmeng;Hsieh, Chen-Lin;Shemshedini, Lirim
通讯作者：
Shemshedini, Lirim