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Parallel p53 and RB1 tumor-suppressor pathways. The Arf and Ink4a proteins encoded by the CDKN2A gene regulate p53 and RB1 function, respectively. Ink4A inhibits cyclin D phosphorylation of RB1 to prevent cell-cycle progression. Arf blocks MDM2-mediated inhibition of p53, leading to apoptosis through BH3-only proteins.
