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CDK4 and CDK6 are important CDKs members that regulated the transition from G1 to S phase and bind to Cyclin Ds (D1, D2 and D3) to form CDK4/6-Cyclin complex after being activated by mitotic signals, while the over-activated CDK4/6 destabilizes the genome and chromosome, leading to uncontrolled proliferation and ultimately abnormal cell cycle regulation [44]

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