JBC：发现新的p53-p21通路的调节因子

TBP（TATA结合蛋白）是转录因子TFⅡD的组分之一。TBP类似蛋白(TLP)能够增强基因表达，研究发现它与细胞发育、细胞周期调控及细胞凋亡息息相关。近日，来自日本千叶大学的研究人员发现，TLP介导了p53-p21通路的调节作用。相关论文发表在4月18日的The Journal of Biological Chemistry。

TLP过表达的人类细胞，尤其是在含有p53的细胞，生长速率下降，G1期细胞比例增加。研究发现，TLP刺激了生长有关的基因包括p21(p21Waf1/Cip1)的表达。通过启动子荧光素酶报告基因分析发现，TLP介导了p21上游启动子的激活。

p53结合序列定位于p21上游启动子，而p53自身也与TLP介导的转录激活有关。他们发现，TLP与p53彼此结合，协同的增强了上游启动子的活性。而且，TLP能够特异性的激活内源性上游启动子的转录，p53也参与了该激活作用。

依托泊苷是一种细胞周期特异性抗肿瘤药物。使用依托泊苷处理后，也导致了上游启动子激活以及核内TLP及p53的积聚。结果表明，上游启动子与内源性TLP及p53有关，TLP能够增强p53招募。

该研究表明，TLP介导了由p53控制的p21上游启动子的转录激活。由于p53与癌症发生密切相关，TLP有可能也会成为新的癌症治疗靶点。

doi: 10.1074/jbc.M112.369629
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TATA-binding protein (TBP)-like protein is required for p53-dependent transcriptional activation of an upstream promoter of the p21Waf1/Cip1 gene

Hidefumi Suzuki, Ryo Ito, Kaori Ikeda and Taka-aki Tamura.

TBP-like protein (TLP) is involved in development, checkpoint, and apoptosis through potentiation of gene expression.TLP-overexpressing human cells, especially p53-containing cells, exhibited a decreased growth rate and increased proportion of G1-phase cells.TLP stimulated expression of several growth-related genes including p21 (p21Waf1/Cip1). TLP-mediated activation of the p21 upstream promoter in cells was shown by a luciferase promoter reporter assay.The p53-binding sequence located in the p21 upstream promoter and p53 itself are required for TLP-mediated transcriptional activation.TLP and p53 bound to each other, and synergistically enhanced activity of the upstream promoter.TLP specifically activated transcription from the endogenous upstream promoter, and p53 was required for this activation.Etoposide treatment also resulted in activation of the upstream promoter as well as nuclear accumulation of TLP and p53.Moreover, the upstream promoter was associated with endogenous p53 and TLP, and the p53 recruitment was enhanced by TLP.The results of the present study suggest that TLP mediates p53-governed transcriptional activation of the p21 upstream promoter.