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Mitogens drive cell cycle progression by induction of cyclinD and inactivation of the retinoblastoma (Rb) protein

Walter Kolch, Ashwin Kotwaliwale, Keith Vass and Petra Janosch

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Figure 3. Mitogens drive cell cycle progression by induction of cyclinD and inactivation of the retinoblastoma (Rb) protein. The cell cycle is driven by the co-ordinated activation of the cyclin-dependent kinases (CDKs). Whereas the CDKs are expressed throughout the cycle, their activating subunits – the cyclins – oscillate between rapid synthesis and degradation. The interface between mitogens and the cell cycle is cyclinD (and to a lesser extent cyclinE), whose expression is induced by mitogens. CyclinD- and cyclinE-dependent kinases phosphorylate (P) and thereby disable the Rb tumour suppressor protein, which is a principal checkpoint controlling the progression from G1 to S phase. Inactivation of the Rb protein marks the restriction point at which cell-cycle progression becomes independent of mitogens. Inactivated Rb releases E2F transcription factors, which stimulate the expression of downstream cyclins and other genes that are required for DNA synthesis (fig003wkg).

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