Shaulian E, Haviv I, Shaul Y, Oren M
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Oncogene. 1995 Feb 16;10(4):671-80.
We have previously shown that monomeric p53 can transactivate target genes in vivo and that C-terminal fragments of p53 are oncogenic. To further elaborate these findings a series of C-terminal truncations of p53 was generated. The transactivation capacity and the ability of the truncated p53 to suppress oncogene-mediated transformation were studied. We found that p53 truncated at amino acid 303 (p53wtdl303) can still function in both assays, though less efficiently than full length wild type (wt) p53. Transforming C-terminal fragments inhibited transactivation induced by full length wt p53. Surprisingly, they also inhibited transactivation by wtdl303, with which they do not share any overlapping sequences. Furthermore, the C-terminal fragments repressed the transactivation domains of several viral and cellular transcriptional activators. These data raise the possibility that the C-terminal domain of p53 may compete with the p53 transactivation domain for a common basal transcription factor.
我们之前已经表明，单体p53能够在体内反式激活靶基因，并且p53的C末端片段具有致癌性。为了进一步阐述这些发现，我们构建了一系列p53的C末端截短体。研究了截短型p53的反式激活能力以及抑制癌基因介导的转化的能力。我们发现，在氨基酸303处截短的p53（p53wtdl303）在这两种检测中仍能发挥作用，尽管效率低于全长野生型（wt）p53。具有转化能力的C末端片段抑制全长wt p53诱导的反式激活。令人惊讶的是，它们也抑制wtdl303的反式激活，而它们与wtdl303没有任何重叠序列。此外，C末端片段抑制几种病毒和细胞转录激活因子的反式激活结构域。这些数据增加了一种可能性，即p53的C末端结构域可能与p53反式激活结构域竞争共同的基础转录因子。
