Zeng X, Levine A J, Lu H
Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA.
Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6681-6. doi: 10.1073/pnas.95.12.6681.
The transactivation activity of the p53 tumor suppressor protein is critical for regulating cell growth and apoptosis. We describe the identification of a transcription factor that is functionally similar to p53 and contains the same DNA binding and transcription activities specific for the p53 responsive DNA element (p53RE). This protein was highly purified through chromatography from HeLa cell extracts. The purified protein was able to bind specifically to the p53RE derived from a p21(waf1) promoter and to stimulate p53RE-dependent transcription but not basal transcription in vitro. Its DNA-binding activity was inhibited by the wild type but not mutant p53RE-containing DNA oligomers. Also, this p53RE-binding activity was found in human p53 null Saos-2 osteosarcoma and H1299 small cell lung carcinoma cells. Interestingly, this activity exhibited a p53RE sequence preference that was distinct from the p53 protein. The activity is neither p53 nor p73, because anti-p53 or anti-73 antibodies were unable to detect this purified protein nor were the antibodies able to alter the p53-like activity, the p53RE-protein complex. These results demonstrate that, besides p73, an additional p53-like protein exists in cells, which is named NBP for non-p53, p53RE binding protein.
p53肿瘤抑制蛋白的反式激活活性对于调节细胞生长和凋亡至关重要。我们描述了一种转录因子的鉴定，该转录因子在功能上与p53相似，并具有与p53反应性DNA元件（p53RE）特异性相同的DNA结合和转录活性。通过色谱法从HeLa细胞提取物中高度纯化了这种蛋白质。纯化后的蛋白质能够特异性结合源自p21（waf1）启动子的p53RE，并在体外刺激依赖p53RE的转录，但不刺激基础转录。其DNA结合活性受到野生型但不受到含突变p53RE的DNA寡聚物的抑制。此外，在人p53缺失的Saos-2骨肉瘤细胞和H1299小细胞肺癌细胞中也发现了这种p53RE结合活性。有趣的是，这种活性表现出与p53蛋白不同的p53RE序列偏好。该活性既不是p53也不是p73，因为抗p53或抗73抗体无法检测到这种纯化的蛋白质，这些抗体也无法改变p53样活性，即p53RE-蛋白质复合物。这些结果表明，除了p73之外，细胞中还存在另一种p53样蛋白，它被命名为NBP，即非p53、p53RE结合蛋白。
