USP7/HAUSP promotes the sequence-specific DNA binding activity of p53.
USP7/HAUSP promotes the sequence-specific DNA binding activity of p53.
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DOI：
10.1371/journal.pone.0013040
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发表时间：
2010-09-27
期刊：
影响因子：
3.7
通讯作者：
Frappier L
中科院分区：
文献类型：
--
作者：
Sarkari F;Sheng Y;Frappier L
p53肿瘤抑制因子通过协调不同的基因表达程序来引起细胞对应激刺激的反应。该功能严重依赖于p53通过以序列特异性方式结合靶基因的启动子而作为转录因子发挥功能的能力。p53核心结构域的DNA结合活性通过C-末端区域的翻译后修饰进行调节。在这里，我们表明，泛素特异性蛋白酶，USP 7或HAUSP，已知稳定p53，也调节序列特异性DNA结合介导的核心结构域的p53在体外。这种调节取决于USP 7和p53的C-末端调节区之间的相互作用。然而，我们的数据表明，这种效果是不介导的N-末端结构域的USP 7先前显示结合p53，而是涉及USP 7的C-末端结构域，是独立的去泛素化活性的USP 7。与我们的体外观察一致，我们发现细胞中催化失活的USP 7的过表达促进p53与其靶序列的结合和p21表达，而不增加p53蛋白的水平。我们还发现USP 7 C-末端结构域足以诱导p21。我们的研究结果表明，一种新的模式的调节p53功能的USP 7，这是独立的USP 7去泛素化活性。
The p53 tumor suppressor invokes cellular responses to stressful stimuli by coordinating distinct gene expression programs. This function relies heavily on the ability of p53 to function as a transcription factor by binding promoters of target genes in a sequence specific manner. The DNA binding activity of the core domain of p53 is subject to regulation via post-translational modifications of the C-terminal region. Here we show that the ubiquitin specific protease, USP7 or HAUSP, known to stabilize p53, also regulates the sequence-specific DNA binding mediated by the core domain of p53 in vitro. This regulation is contingent upon interaction between USP7 and the C-terminal regulatory region of p53. However, our data suggest that this effect is not mediated through the N-terminal domain of USP7 previously shown to bind p53, but rather involves the USP7 C-terminal domain and is independent of the deubiquitylation activity of USP7. Consistent with our in vitro observations, we found that overexpression of catalytically inactive USP7 in cells promotes p53 binding to its target sequences and p21 expression, without increasing the levels of p53 protein. We also found that the USP7 C-terminal domain was sufficient for p21 induction. Our results suggest a novel mode of regulation of p53 function by USP7, which is independent of USP7 deubiquitylating activity.
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影响因子：
6.7
作者：
Sarkari F;Sanchez-Alcaraz T;Wang S;Holowaty MN;Sheng Y;Frappier L
通讯作者：
Frappier L
影响因子：
10.5
作者：
Resnick-Silverman, L;St Clair, S;Manfredi, JJ
通讯作者：
Manfredi, JJ
影响因子：
64.8
作者：
Green, Douglas R.;Kroemer, Guido
通讯作者：
Kroemer, Guido
影响因子：
16
作者：
Saridakis, V;Sheng, Y;Frappier, L
通讯作者：
Frappier, L
影响因子：
64.5
作者：
Hu, M;Li, PW;Shi, YG
通讯作者：
Shi, YG