Sang N, Giordano A
Department of Pathology, Sbarro Institute for Cancer Research and Molecular Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennslyvania 19107, USA.
J Cell Physiol. 1997 Feb;170(2):182-91. doi: 10.1002/(SICI)1097-4652(199702)170:2<182::AID-JCP10>3.0.CO;2-K.
By interacting with key regulatory proteins such as the pRb family, cyclins, cyclin-dependent kinases and p300/CBP of host cells, adenoviral E1A interferes with various cellular processes to provide a suitable environment for the replication of viruses. E1A may promote DNA synthesis and cell cycle progression, immortalize rodent cells in culture and transform cultured cells in cooperation with E1B, Ras, or other oncoproteins. Both extreme N terminus and conserved region 1 of E1A are required for the immortalization and the transformation of rodent cells, transcriptional repression and specific induction of the expression of cellular genes such as the proliferating cell nuclear antigen (PCNA) and heat shock protein 70 (HSP70). Although the molecular mechanisms of these functions of E1A are not fully understood, it is believed that protein-protein interactions may play essential roles. In this communication, we report that a new set of cellular proteins with apparent molecular weight of 200, 90, 45, 30, and 28 specifically associate with the extreme N terminus of E1A. Further analysis demonstrate that these associations do not depend on E1A's association with p300 or pRB. Neither the 30 kDa nor the 28 kDa polypeptide is identical to Cdc2 or Cdk2. The region of E1A required for the protein interaction is also required for the recently identified N-terminal transactivation activity of E1A. Our observations suggest that in addition to p300/CBP, the new set of cellular proteins may be involved in the functional complexity of the N terminus of E1A, thus predicting a p300/CBP independent pathway.
通过与宿主细胞的关键调节蛋白如pRb家族、细胞周期蛋白、细胞周期蛋白依赖性激酶和p300/CBP相互作用，腺病毒E1A干扰各种细胞过程，为病毒复制提供合适的环境。E1A可促进DNA合成和细胞周期进程，使培养中的啮齿动物细胞永生化，并与E1B、Ras或其他癌蛋白协同转化培养细胞。E1A的极端N末端和保守区域1对于啮齿动物细胞的永生化和转化、转录抑制以及细胞基因如增殖细胞核抗原（PCNA）和热休克蛋白70（HSP70）表达的特异性诱导都是必需的。尽管E1A这些功能的分子机制尚未完全了解，但据信蛋白质-蛋白质相互作用可能起关键作用。在本通讯中，我们报告了一组新的细胞蛋白，其表观分子量分别为200、90、45、30和28，它们特异性地与E1A的极端N末端结合。进一步分析表明，这些结合不依赖于E1A与p300或pRB的结合。30 kDa和28 kDa的多肽都与Cdc2或Cdk2不同。E1A中蛋白质相互作用所需的区域也是最近确定的E1A N末端反式激活活性所必需的。我们的观察结果表明，除了p300/CBP外，这组新的细胞蛋白可能参与了E1A N末端的功能复杂性，从而预示了一条不依赖于p300/CBP的途径。
