Felsani A, Mileo A M, Paggi M G
Istituto di Neurobiologia e Medicina Molecolare, CNR, Rome, Italy.
Oncogene. 2006 Aug 28;25(38):5277-85. doi: 10.1038/sj.onc.1209621.
RB, the most investigated tumor suppressor gene, is the founder of the RB family of growth/tumor suppressors, which comprises also p107 (RBL1) and Rb2/p130 (RBL2). The protein products of these genes, pRb, p107 and pRb2/p130, respectively, are also known as 'pocket proteins', because they share a 'pocket' domain responsible for most of the functional interactions characterizing the activity of this family of cellular factors. The interest in these genes and proteins springs essentially from their ability to regulate negatively cell cycle processes and for their ability to slow down or abrogate neoplastic growth. The pocket domain of the RB family proteins is dramatically hampered in its functions by the interference of a number of proteins produced by the small DNA viruses. In the last two decades, the 'viral hypothesis' of cancer has received a considerable renewed impulse from the notion that small DNA viruses, such as Adenovirus, Human papillomavirus (HPV) and Polyomavirus, produce factors that can physically interact with major cellular regulators and alter their function. These viral proteins (oncoproteins) act as multifaceted molecular devices that have evolved to perform very specific tasks. Owing to these features, viral oncoproteins have been widely employed as invaluable experimental tools for the identification of several key families of regulators, particularly of the cell cycle homeostasis. Adenovirus early-region 1A (E1A) is the most widely investigated small DNA tumor virus oncoprotein, but relevant interest in human oncology is raised by the E1A-related E7 protein from transforming HPV strains and by Polyomavirus oncoproteins, particularly large and small T antigens from Simian virus 40, JC virus and BK virus.
RB是研究最多的肿瘤抑制基因，是生长/肿瘤抑制因子RB家族的创始成员，该家族还包括p107（RBL1）和Rb2/p130（RBL2）。这些基因的蛋白质产物分别为pRb、p107和pRb2/p130，也被称为“口袋蛋白”，因为它们共享一个“口袋”结构域，该结构域负责该细胞因子家族活性的大多数功能相互作用。对这些基因和蛋白质的兴趣主要源于它们负向调节细胞周期进程的能力以及减缓或消除肿瘤生长的能力。一些小DNA病毒产生的多种蛋白质的干扰会严重阻碍RB家族蛋白质的口袋结构域的功能。在过去二十年中，癌症的“病毒假说”因以下观点而获得了相当大的新推动力：腺病毒、人乳头瘤病毒（HPV）和多瘤病毒等小DNA病毒产生的因子可与主要细胞调节因子发生物理相互作用并改变其功能。这些病毒蛋白（癌蛋白）充当多面分子装置，进化而来执行非常特定的任务。由于这些特性，病毒癌蛋白已被广泛用作鉴定几个关键调节因子家族，特别是细胞周期稳态调节因子家族的宝贵实验工具。腺病毒早期区域1A（E1A）是研究最广泛的小DNA肿瘤病毒癌蛋白，但来自致瘤性HPV毒株的E1A相关E7蛋白以及多瘤病毒癌蛋白，特别是来自猴病毒40、JC病毒和BK病毒的大T抗原和小T抗原，在人类肿瘤学中引起了相关关注。
