NSPc1 is a cell growth regulator that acts as a transcriptional repressor of p21Waf1/Cip1 via the RARE element.
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.
Gong
Yanhua
Y
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, National Human Genome Center, Beijing 100005, China.
Yue
Jiping
J
Wu
Xudong
X
Wang
Xu
X
Wen
Jianyan
J
Lu
Lifang
L
Peng
Xiaozhong
X
Qiang
Boqin
B
Yuan
Jiangang
J
D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D063150:Polycomb Repressive Complex 1; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D020218:Response Elements; D047490:Retinoid X Receptor alpha / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism / Q000502:physiology*
C493956:CDKN1A protein, human; D002352:Carrier Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; C496334:PCGF1 protein, human; D012097:Repressor Proteins; D047490:Retinoid X Receptor alpha; D063150:Polycomb Repressive Complex 1; D044767:Ubiquitin-Protein Ligases