Massimi P, Pim D, Storey A, Banks L
International Centre for Genetic Engineering and Biotechnology, AREA Science Park, Trieste, Italy.
Oncogene. 1996 Jun 6;12(11):2325-30.
The major transforming protein of HPV-16 is encoded by the E7 gene. This has been shown to cooperate with EJ-ras in the immortalisation of primary rodent cells and with the viral E6 gene in the immortalisation of primary human keratinocytes. HPV-16 E7 protein has been shown to bind to a number of cellular proteins involved in the control of cell growth; including pRB, p107 and cyclin A. Loss of pRb or p107 binding results in the loss of transforming activity. In this paper we demonstrate that HPV-16 E7 can also complex with the core component of TFIID, the TATA Box Binding Protein (TBP). This interaction is partly dependent upon phosphorylation of the E7 protein by cellular casein kinase II (CKII), since phosphorylation of E7 by CKII increases the affinity with which E7 binds TBP. Similar results are also obtained with the Adenovirus Ela protein, indicating a conservation of function between these two viral oncoproteins. Mutation of the CKII site to two acidic amino acids significantly increases the affinity of E7 for TBP, indicating that the incorporation of two negative charges at this region of E7 is important in regulating the interaction with TBP.
人乳头瘤病毒16型（HPV - 16）的主要转化蛋白由E7基因编码。研究表明，该蛋白在原代啮齿动物细胞永生化过程中与EJ - ras协同作用，在原代人角质形成细胞永生化过程中与病毒E6基因协同作用。HPV - 16 E7蛋白已被证明可与多种参与细胞生长调控的细胞蛋白结合，包括pRB、p107和细胞周期蛋白A。pRb或p107结合的丧失会导致转化活性的丧失。在本文中，我们证明HPV - 16 E7还可与TFIID的核心成分——TATA盒结合蛋白（TBP）形成复合物。这种相互作用部分依赖于细胞酪蛋白激酶II（CKII）对E7蛋白的磷酸化，因为CKII对E7的磷酸化增加了E7与TBP结合的亲和力。腺病毒Ela蛋白也得到了类似的结果，表明这两种病毒癌蛋白之间存在功能保守性。将CKII位点突变为两个酸性氨基酸会显著增加E7对TBP的亲和力，表明在E7的该区域引入两个负电荷对于调节与TBP的相互作用很重要。
