Résumé
The orderly progression through the cell cycle is mediated by the sequential activation of several cyclin/cyclin-dependent kinase (cdk) complexes. These kinases phosphorylate a number of cellular substrates, among which are the product of the retinoblastoma gene, pRB, and the pRB-related proteins p107 and p130. Phosphorylation of these proteins in late G1 causes their release from the heterodimeric transcription factors E2F/DP. This results in the transcriptional activation of E2F-responsive genes which encode proteins that either directly control cell-cycle progression or function in metabolic processes linked to the cell cycle. Thus E2F/DP complexes are key signal transducers connecting the cell cycle machinery with the transcriptional control of sets of genes that mediate the passage through the G1 and S phases of the cell cycle. This critical regulatory pathway, which gates cell cycle progression, is often disrupted during the pathogenesis of many mammalian tumors. It also plays a pivotal role in animal development and in promoting cellular differentiation. We review the current state of knowledge regarding this pRB/E2F pathway. (Figure 1.1)