TBP（TATA結合蛋白）是轉錄因子TFⅡD的組分之一。TBP類似蛋白(TLP)能夠增強基因表達，研究發現它與細胞發育、細胞周期調控及細胞凋亡息息相關。近日，來自日本千葉大學的研究人員發現，TLP介導了p53-p21通路的調節作用。相關論文發表在4月18日的The Journal of Biological Chemistry。
TLP過表達的人類細胞，尤其是在含有p53的細胞，生長速率下降，G1期細胞比例增加。研究發現，TLP刺激了生長有關的基因包括p21(p21Waf1/Cip1)的表達。通過啟動子螢光素酶報告基因分析發現，TLP介導了p21上遊啟動子的激活。
p53結合序列定位於p21上遊啟動子，而p53自身也與TLP介導的轉錄激活有關。他們發現，TLP與p53彼此結合，協同的增強了上遊啟動子的活性。而且，TLP能夠特異性的激活內源性上遊啟動子的轉錄，p53也參與了該激活作用。
依託泊苷是一種細胞周期特異性抗腫瘤藥物。使用依託泊苷處理後，也導致了上遊啟動子激活以及核內TLP及p53的積聚。結果表明，上遊啟動子與內源性TLP及p53有關，TLP能夠增強p53招募。
該研究表明，TLP介導了由p53控制的p21上遊啟動子的轉錄激活。由於p53與癌症發生密切相關，TLP有可能也會成為新的癌症治療靶點。（生物谷Deepblue編譯）
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.