NSPc1 is a cell growth regulator that acts as a transcriptional repressor of p21Waf1/Cip1 via the RARE element.
NSPc1 is a cell growth regulator that acts as a transcriptional repressor of p21Waf1/Cip1 via the RARE element.
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NSPc1 是一种细胞生长调节剂，通过 RARE 元件充当 p21Waf1/Cip1 的转录抑制因子
DOI：
10.1093/nar/gkl834
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发表时间：
2006
影响因子：
14.9
通讯作者：
Yuan J
中科院分区：
文献类型：
--
作者：
Gong Y;Yue J;Wu X;Wang X;Wen J;Lu L;Peng X;Qiang B;Yuan J
哺乳动物多梳蛋白在细胞周期调控和肿瘤发生中起着重要作用。神经系统多聚体1(NSPc1)是新近发现的一种转录抑制因子，与PcG蛋白Bmi-1高度同源。在本文中，我们发现NSPc1可以促进肿瘤细胞周期的进展和细胞的增殖。半定量RT-PCR结果显示，除p21Waf1/Cip1外，NSPc1不影响大多数细胞周期蛋白依赖性蛋白依赖性蛋白激酶(CDK)抑制剂的表达水平。抑制活性检测、染色质免疫沉淀和DNA拉下实验均证实，NSPc1在体内通过与p21Waf1/Cip1启动子(−1357~−1083)区域结合来抑制p21Waf1/Cip1的表达，并且这种抑制作用依赖于p21Waf1/Cip1启动子区域内的维甲酸反应元件(稀有元件)。进一步分析表明，NSPc1在体外和体内都能与RA受体竞争稀有元素。综上所述，我们的结果支持NSPc1通过稀有元素下调p21Waf1/Cip1在肿瘤细胞生长中的积极作用的假说，稀有元素直接将PCGS的转录抑制与CDKI和RA信号通路联系起来。
The mammalian polycomb group proteins play an important role in cell cycle control and tumorigenesis. Nervous system polycomb 1 (NSPc1) is a newly identified transcription repressor, highly homologous with PcG protein Bmi-1. In this article, we showed that NSPc1 could promote tumor cell cycle progression and cell proliferation. Semi-quantitative RT–PCR showed that NSPc1 did not affect the expression levels of most Cyclin-depentent kinases (CDK) inhibitors except for p21Waf1/Cip1. Repression activity assays, chromatin immunoprecipitation (ChIP) and DNA pulldown assays all verified that NSPc1 represses the expression of p21Waf1/Cip1 by binding to the (−1357 to −1083) region of the p21Waf1/Cip1 promoter in vivo, and the repression effect is dependent on the retinoid acid response element (RARE element) within the above region of the p21Waf1/Cip1 promoter. Further analysis showed that NSPc1 could compete the RARE element site with RA receptors both in vitro and in vivo. Taken together, our results support the hypothesis that NSPc1 has a positive role in tumor cell growth by down-regulating p21Waf1/Cip1 via the RARE element, which directly connects transcriptional repression of PcGs to CDKIs and RA signaling pathways.
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影响因子：
64.5
作者：
ELDEIRY, WS;TOKINO, T;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
影响因子：
5.3
作者：
Dulic, V;Stein, GH;Reed, SI
通讯作者：
Reed, SI
DOI：
10.1073/pnas.150006697
发表时间：
2000-08-15
影响因子：
11.1
作者：
Claassen, GF;Hann, SR
通讯作者：
Hann, SR
影响因子：
11.2
作者：
Carson, JP;Zhang, NY;Christman, MF
通讯作者：
Christman, MF
影响因子：
11.4
作者：
KANNO, M;HASEGAWA, M;TANIGUCHI, M
通讯作者：
TANIGUCHI, M