Cell Cycle Control

The cell cycle involves regulated cell growth, replication, and division. The cell cycle includes four distinct phases: G1 (gap phase 1), S (DNA synthesis), G2 (gap phase 2), and M (mitosis). Cell cycle regulation (both activation and inhibition) is dependent upon specific cell cycle checkpoints, which prevent abnormal cell cycle activation and continuation. For example, the G2/M checkpoint ensures that cells containing damaged DNA do not enter mitosis. These cell cycle checkpoints are controlled by the coordinated action of CDK+cyclin binding pairs including CDK4/6+cyclin D, RB1/E2F, CDK2+cyclin E, CDK2+cyclin A, CDK1+cyclin A, CDK1+cyclin B.

Figure 1. The cell cycle is a set of processes through which a cell divides to become two identical daughter cells. The cell cycle encompasses four phases including G1 (gap phase 1), S (DNA synthesis), G2 (gap phase 2), and M (mitosis). The cell cycle is controlled by the complex interplay of cyclin-dependent kinases (CDK -1, -2, -4, -6, -8, -12) and cyclins (cyclin -A, -B, -D, -E). Heterodimers of cyclins and CDKs function at different points in the cycle. There are several checks and balances, called checkpoints, in the cell cycle to ensure integrity of daughter cells. Checkpoints include the G1/S checkpoint and the G2/M checkpoint. Of particular relevance, p21 and p27 function as regulators of the G1 and S checkpoints. These checkpoints become important in the setting of DNA damage. DNA damage activates these checkpoints to ensure genomic integrity by repairing damaged DNA or forcing the cell to enter a programmed cell death pathway if DNA cannot be repaired. Checkpoints and DNA damage responses are altered in numerous malignancies. Specific nodes in the pathway that are therapeutically actionable are noted. Click here to open a larger version of this image in a new window.

Upstream Pathways

Diseases in Which Pathway is Aberrantly Activated

Therapies That Target This Pathway

CDK inhibitors
CDK1 inhibitors
CDK2 inhibitors
CDK4/6 inhibitors

Genes Involved in the Pathway

Last Updated: July 1, 2016

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