One way that mitogens stimulate cell proliferation is by inhibiting the Rb protein.

(A) In the absence of mitogens, dephosphorylated Rb protein holds specific gene regulatory proteins in an inactive state; these gene regulatory proteins are required to stimulate the transcription of target genes that encode proteins needed for cell proliferation. (B) Mitogens bind to cell-surface receptors and activate intracellular signaling pathways that lead to the formation and activation of the G₁-Cdk and G₁/S-Cdk complexes mentioned earlier. These complexes phosphorylate, and thereby inactivate the Rb protein. The gene regulatory proteins are now free to activate the transcription of their target genes, leading to cell proliferation.

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