p202, an interferon-inducible negative regulator of cell growth, is a target of the adenovirus E1A protein.
p202, an interferon-inducible negative regulator of cell growth, is a target of the adenovirus E1A protein.
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p202 是一种干扰素诱导的细胞生长负调节因子，是腺病毒 E1A 蛋白的靶标。
作者：
Xin,H;D'Souza,S;Fang,L;Lengyel,P;Choubey,D
研究表明，人腺病毒编码的E1a蛋白通过与细胞蛋白的靶向相互作用促进细胞增殖，而细胞蛋白是细胞生长的关键负调控因子。E1a蛋白的靶标包括视网膜母细胞瘤肿瘤抑制蛋白(PRB)。由于p202是一种干扰素诱导的小鼠蛋白(52 KDa)，部分通过pRB/E2F途径负向调节细胞生长，因此我们测试了p202是否是腺病毒编码的E1a蛋白功能失活的靶标。在这里，我们报告了E1a蛋白的表达克服了p202介导的细胞生长抑制，这与p202介导的对E2F转录活性的抑制减轻了相关。此外，E1a蛋白解除了p202对包括Pocket蛋白在内的E2F复合体的DNA结合活性的抑制。此外，E1a蛋白在体外和体内都与p202结合，并且E1a蛋白保守区2(CR2)上四个氨基酸的缺失显著降低了E1a与p202的结合。有趣的是，p202在低血清条件下的异位表达显著减少了E1a介导的细胞凋亡。综上所述，我们的观察结果支持这样的观点，即p202和腺病毒E1a蛋白在功能上相互抵消，E1a蛋白以p202为靶点促进细胞增殖。
Studies have revealed that human adenovirus-encoded E1A protein promotes cell proliferation through the targeted interaction with cellular proteins that act as key negative regulators of cell growth. The targets of E1A protein include the retinoblastoma tumor suppressor protein (pRb). Because p202, an interferon (IFN)-inducible murine protein (52-kDa), negatively regulates cell growth in part through the pRb/E2F pathway, we tested whether the p202 is a target of the adenovirus-encoded E1A protein for functional inactivation. Here we report that the expression of E1A protein overcame p202-mediated inhibition of cell growth and this correlated with an alleviation of p202-mediated inhibition of the transcriptional activity of E2F. Furthermore, E1A protein relieved p202-mediated inhibition of the specific DNA-binding activity of E2F complexes, including those containing the pocket proteins. Additionally, the E1A protein bound to p202 both in vitro and in vivo and a deletion of four amino acids in the conserved region 2 (CR2) of E1A protein significantly reduced the binding of E1A to p202. Interestingly, ectopic expression of p202 under reduced serum conditions significantly reduced E1A-mediated apoptosis. Taken together, our observations provide support to the idea that the p202 and adenovirus E1A protein functionally counteract each other and E1A protein targets p202 to promote cell proliferation.