Macleod K
Department of Molecular & Cellular Pathology, University of Dundee, Ninewells Hospital, Dundee DD1 9SY, UK.
Curr Opin Genet Dev. 1999 Feb;9(1):31-9. doi: 10.1016/s0959-437x(99)80005-7.
Our understanding of how RB and E2F-1 function has progressed significantly from the model in which RB negatively regulates expression of genes required for S phase by binding to and inhibiting E2F-1. Both RB and E2F-1 have been shown recently to possess additional properties and mechanisms of regulation relevant to developmental and tumorigenic processes. In particular, it is now realised that RB has E2F-independent tumor suppressor functions which rely upon the ability of RB to induce differentiation. For its part, E2F-1 is unique amongst E2F family members in its capacity to induce apoptosis and this function is clearly relevant to our appreciation of E2F-1 as a conditional tumor suppressor. E2F-1 can induce both apoptosis and S-phase transition and whether E2F-1 acts as an oncogene or a tumor-suppressor gene may depend on the extent to which E2F-1 induces apoptosis as opposed to G1/S transition.
我们对RB和E2F-1功能的理解，已从RB通过结合并抑制E2F-1来负向调节S期所需基因表达的模型，取得了显著进展。最近研究表明，RB和E2F-1都具有与发育和肿瘤发生过程相关的其他特性和调控机制。特别是，现在已经认识到RB具有不依赖E2F的肿瘤抑制功能，该功能依赖于RB诱导分化的能力。就E2F-1而言，它在诱导凋亡的能力方面在E2F家族成员中是独特的，并且该功能显然与我们将E2F-1视为条件性肿瘤抑制因子的认识相关。E2F-1可以诱导凋亡和S期转变，并且E2F-1作为癌基因还是肿瘤抑制基因，可能取决于E2F-1诱导凋亡相对于G1/S转变的程度。
