TBP（TATA結(jié)合蛋白）是轉(zhuǎn)錄因子TFⅡD的組分之一,。TBP類似蛋白(TLP)能夠增強(qiáng)基因表達(dá),，研究發(fā)現(xiàn)它與細(xì)胞發(fā)育,、細(xì)胞周期調(diào)控及細(xì)胞凋亡息息相關(guān)。近日,，來自日本千葉大學(xué)的研究人員發(fā)現(xiàn),，TLP介導(dǎo)了p53-p21通路的調(diào)節(jié)作用。相關(guān)論文發(fā)表在4月18日的The Journal of Biological Chemistry,。
TLP過表達(dá)的人類細(xì)胞,，尤其是在含有p53的細(xì)胞，生長速率下降,，G1期細(xì)胞比例增加,。研究發(fā)現(xiàn)，TLP刺激了生長有關(guān)的基因包括p21(p21Waf1/Cip1)的表達(dá),。通過啟動(dòng)子熒光素酶報(bào)告基因分析發(fā)現(xiàn),，TLP介導(dǎo)了p21上游啟動(dòng)子的激活。
p53結(jié)合序列定位于p21上游啟動(dòng)子,，而p53自身也與TLP介導(dǎo)的轉(zhuǎn)錄激活有關(guān),。他們發(fā)現(xiàn)，TLP與p53彼此結(jié)合,，協(xié)同的增強(qiáng)了上游啟動(dòng)子的活性,。而且，TLP能夠特異性的激活內(nèi)源性上游啟動(dòng)子的轉(zhuǎn)錄,，p53也參與了該激活作用,。
依托泊苷是一種細(xì)胞周期特異性抗腫瘤藥物。使用依托泊苷處理后,，也導(dǎo)致了上游啟動(dòng)子激活以及核內(nèi)TLP及p53的積聚,。結(jié)果表明，上游啟動(dòng)子與內(nèi)源性TLP及p53有關(guān),，TLP能夠增強(qiáng)p53招募,。
該研究表明，TLP介導(dǎo)了由p53控制的p21上游啟動(dòng)子的轉(zhuǎn)錄激活,。由于p53與癌癥發(fā)生密切相關(guān),，TLP有可能也會成為新的癌癥治療靶點(diǎn)。（生物谷Deepblue編譯）
doi: 10.1074/jbc.M112.369629
PMC:
PMID:
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.
