Deb S, Brown D, Lega H, Deb S
Int J Oncol. 1995 Jan;6(1):243-9.
In this communication we show that overexpression of the human TATA-binding protein (TBP) activates a synthetic promoter with p53-binding sites in the presence of wild-type p53. No activation is observed in the absence of wild-type p53 in Saos-2 cells. Perhaps, TBP is limiting in these cells for the p53-mediated activation, and p53 activates promoters with p53-binding sites via its interaction with TBP. Using in vivo transient transfection-transcription assays, we also show that wild-type human p53 inhibits simian virus 40 (SV40) late promoter transactivation by SV40 T antigen, but excess T antigen partially releases this inhibition. Recently both T antigen and p53 have been shown to interact with TBP. The inhibition of T antigen-mediated SV40 late promoter activation by p53 or the inhibition of p53-mediated activation of a promoter with p53-binding sites by T antigen is not released by an overexpression of TBP. Thus, the transcriptional antagonism between p53 and T antigen are not at the level of competition for TBP. Possibly, the two proteins poison each other so that they cannot interact with the transcription machinery.
在本交流中，我们表明，在野生型p53存在的情况下，人TATA结合蛋白（TBP）的过表达可激活带有p53结合位点的合成启动子。在Saos-2细胞中，缺乏野生型p53时未观察到激活现象。也许，在这些细胞中TBP对于p53介导的激活是有限的，并且p53通过与TBP相互作用来激活带有p53结合位点的启动子。使用体内瞬时转染-转录分析，我们还表明，野生型人p53抑制猿猴病毒40（SV40）晚期启动子被SV40 T抗原的反式激活，但过量的T抗原可部分解除这种抑制。最近已表明T抗原和p53均与TBP相互作用。p53对T抗原介导的SV40晚期启动子激活的抑制作用，或T抗原对带有p53结合位点的启动子的p53介导的激活的抑制作用，不会因TBP的过表达而解除。因此，p53与T抗原之间的转录拮抗作用并非在对TBP的竞争层面。可能，这两种蛋白相互毒害，以至于它们无法与转录机制相互作用。
