Tbx2 directly represses the expression of the p21WAF1 cyclin-dependent kinase inhibitor
Tbx2 directly represses the expression of the p21WAF1 cyclin-dependent kinase inhibitor
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DOI：
10.1158/0008-5472.can-03-3286
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发表时间：
2004-03-01
期刊：
影响因子：
11.2
通讯作者：
Goding, CR
中科院分区：
文献类型：
--
作者：
Prince, S;Carreira, S;Goding, CR
T-box因子在许多组织的发育中起着至关重要的作用，T-box因子基因的突变与多种人类疾病有关。一些T-box因子与癌症有关；例如Tbx2和Tbx3可以抑制复制性衰老，而Tbx3可以与Myc和Ras协同进行细胞转化。p21（WAF1）周期蛋白依赖性激酶抑制剂在DNA损伤后的衰老和细胞周期阻滞中起关键作用。在这里，通过结合体外dna结合、转染和染色质免疫沉淀试验，我们发现Tbx2可以在体外和体内结合并抑制p21启动子。此外，小干扰rna介导的Tbx2表达下调导致p21表达的强烈激活。综上所述，这些结果表明Tbx2是p21表达的一种新的直接调节剂，并对我们理解T-box因子在衰老和肿瘤发生以及发育调节中的作用具有重要意义。
T-box factors play a crucial role in the development of many tissues, and mutations in T-box factor genes have been implicated in multiple human disorders. Some T-box factors have been implicated in cancer; for example, Tbx2 and Tbx3 can suppress replicative senescence, whereas Tbx3 can cooperate with Myc and Ras in cellular transformation. The p21(WAF1) cyclin-dependent kinase inhibitor plays a key role in senescence and in cell cycle arrest after DNA damage. Here, using a combination of in vitro DNA-binding, transfection, and chromatin immunoprecipitation assays, we show that Tbx2 can bind and repress the p21 promoter in vitro and in vivo. Moreover, small interfering RNA-mediated down-regulation of Tbx2 expression results in a robust activation of p21 expression. Taken together, these results implicate Tbx2 as a novel direct regulator of p21 expression and have implications for our understanding of the role of T-box factors in the regulation of senescence and oncogenesis, as well as in development.