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| Modern Genetic Analysis Chapter 15. Regulation of Cell Number: Normal and Cancer Cells Controlling the Cell Proliferation and Death Machinery Figure 15-6. An example of inhibitory control of cell cycle progression. In mammals, the transition from the G1 to S phase requires the phosphorylation of Rb protein by the CDK2cyclin complex. In the presence of damaged DNA, p53 protein is induced, which in turn indices p21 protein. The elevated levels of p21 protein inhibit the protein kinase activity of the CDK2cyclin complex. When the damaged DNA has been repaired, p53 levels drop. In turn, p21 levels decrease, and the inhibition of the CDK2cyclin protein kinase activity is relieved, which allows Rb to be phosphorylated and E2F to become an active transcription factor, permitting the cell to enter S phase. (Adapted from C. J. Sherr and J. M. Roberts, Genes and Development 9, 1995, 1150.)

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