Cell Cycle and Cancer: The G1 Restriction Point and the G1 / S Transition

Understanding the molecular events that commit to the cell cycle has important implications for cancer. Available evidence, mostly derived from human tumors, has revealed frequent alterations in genes involved in the control of the G1 restriction point and the progression from G1 to S phase. Many of the players that participate in these events have been characterized at the biochemical level. They include, among others the cyclin-dependent kinases (Cdk), Cdk4, Cdk6 and Cdk2 and their cognate D- and E-type cyclins, Cdk inhibitors (CKI), and the main Cdk downstream substrates, the retinoblastoma (pRb) family of proteins. Yet, there is little information as how these molecules regulate cell cycle commitment in vivo. The development of mouse strains carrying targeted mutations in these loci is opening new ways to explore the network of molecular pathways that control passage through G1 into the S phase in complex multicellular organisms such as mammals. These strains are also providing new insights as of how misregulation of these processes may lead to cancer development. In this review, we attempt to summarize our current knowledge of the molecular mechanisms that control the G1 / S transition with particular emphasis in those studies carried out in vivo using gene targeted mice.