Microsoft Word - BARBACID-.DOC

At least four Cdk's –Cdk4, Cdk6, Cdk2 and Cdk1– are thought to play key roles during the different phases of the cell cycle (Figure 1). For instance, Cdk4 and Cdk6, two kinases that can only be activated by D-type cyclins, are thought to be essential in allowing cells to exit quiescence (G0) by initiating the sequential phosphorylation of the retinoblastoma protein (pRB). Partially phosphorylated pRB releases certain transcription factors such as the members of the E2F family that in turn facilitate expression of cyclin E.