Davies R, Hicks R, Crook T, Morris J, Vousden K
Ludwig Institute for Cancer Research, St. Mary's Hospital Medical School, London, England.
J Virol. 1993 May;67(5):2521-8. doi: 10.1128/JVI.67.5.2521-2528.1993.
The transforming function of human papillomavirus type 16 (HPV16) E7 has been shown to depend on activities additional to the ability to bind RB. In this paper we describe two further properties of E7 which may also contribute to transformation, an association with a histone H1 kinase at the G2/M phase of the cell cycle and an ability to bind the RB-related protein p107. The region of E7 identified previously as important for RB binding was found to be involved in the association with the kinase and complex formation with p107, although analysis of E7 point mutants within this region revealed a difference in the precise sequence requirement for RB and p107 binding. Association with the kinase activity correlated with the ability to bind RB, but the restriction of the kinase association to the G2/M phase of the cell cycle implies that this activity might not be directly mediated by RB binding. Since kinase-binding-deficient E7 mutants are also transformation defective, this may represent an independent function of E7 which plays a role in the G2/M phase of the cell cycle.
人乳头瘤病毒16型(HPV16)E7的转化功能已被证明不仅取决于其与RB结合的能力,还依赖于其他活性。在本文中,我们描述了E7的另外两个可能也有助于转化的特性,即在细胞周期的G2/M期与组蛋白H1激酶的关联以及与RB相关蛋白p107结合的能力。先前确定对RB结合很重要的E7区域被发现参与了与激酶的关联以及与p107的复合物形成,尽管对该区域内E7点突变体的分析揭示了RB和p107结合在精确序列要求上的差异。与激酶活性的关联与结合RB的能力相关,但激酶关联仅限于细胞周期的G2/M期,这意味着该活性可能不是由RB结合直接介导的。由于激酶结合缺陷的E7突变体也是转化缺陷型,这可能代表了E7在细胞周期G2/M期发挥作用的独立功能。