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. 2019 Jun 20;20(12):3021. doi: 10.3390/ijms20123021

Figure 3.

Figure 3

Cell cycle regulation. In normal cells p16INK4A, encoded by CDKN2A, inhibits the CDK4/6-Cyclin D complex by binding to it and preventing phosphorylation (P) of retinoblastoma (Rb), which holds its binding to E2 factor (E2F) family of transcription factors, switches gene transcription off, and inhibits G1 to S phase. In T-ALL cells, loss of CDKN2A causes loss of p16INK4A. CDK4/6-Cyclin D phosphorylates Rb, which releases E2F and promotes its binding to DNA, enabling gene expression and G1/S transition. Cyclin D/CDK4-6 inhibitors (PD033291 and LEE001) restore cell cycle regulation by binding to the CDK4-6/Cyclin D complex, mimicking p16INK4A function. Black arrows show signal transduction. Red arrows show inhibition.