Fattaey A, Helin K, Harlow E
Massachusetts General Hospital Cancer Center, Charlestown 02129.
Philos Trans R Soc Lond B Biol Sci. 1993 Jun 29;340(1293):333-6. doi: 10.1098/rstb.1993.0075.
The retinoblastoma protein, pRB, appears to play a key role in coordinating the regulation of cell cycle position and transcriptional events. pRB undergoes specific cell-cycle-dependent phosphorylation, being underphosphorylated in G1 and heavily phosphorylated in S, G2, and M. The underphosphorylated form is able to interact with the E2F transcription factor. Recently, we have cloned a cDNA for E2F-1. By using this clone and a series of non-pRB binding mutants, we have been able to show that the binding of pRB to E2F-1 causes inhibition of E2F-mediated transactivation. pRB's inhibition of E2F-mediated transcription would be lost by mutation in the retinoblastoma gene in human tumours, by pRB's interaction with DNA tumour virus oncoproteins, or by phosphorylation during the cell cycle.
视网膜母细胞瘤蛋白pRB似乎在协调细胞周期位置调控和转录事件中发挥关键作用。pRB经历特定的细胞周期依赖性磷酸化，在G1期处于低磷酸化状态，在S期、G2期和M期高度磷酸化。低磷酸化形式能够与E2F转录因子相互作用。最近，我们克隆了E2F - 1的cDNA。通过使用该克隆以及一系列非pRB结合突变体，我们已经能够证明pRB与E2F - 1的结合会导致E2F介导的反式激活受到抑制。在人类肿瘤中，视网膜母细胞瘤基因的突变、pRB与DNA肿瘤病毒癌蛋白的相互作用或细胞周期中的磷酸化都会导致pRB对E2F介导转录的抑制作用丧失。
