negative regulation of cell cycle

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the rate or extent of progression through the cell cycle. [GOC:dph, GOC:go_curators, GOC:tb]

Negative regulation of cell cycle is a fundamental biological process that ensures proper timing and coordination of cell division. It involves a complex interplay of molecular mechanisms that act to inhibit or suppress the progression of the cell cycle through its distinct phases: G1, S, G2, and M. The cell cycle is a tightly controlled process that ensures that cells divide only when necessary and under appropriate conditions. Dysregulation of this process can lead to uncontrolled cell proliferation, a hallmark of cancer. Key players in negative regulation of cell cycle include:

- **Cyclin-dependent kinases (CDKs):** CDKs are enzymes that phosphorylate target proteins, triggering various events in the cell cycle. CDK activity is regulated by their association with cyclins, which are proteins that fluctuate in concentration throughout the cell cycle.
- **CDK inhibitors (CKIs):** CKIs are proteins that bind to and inhibit the activity of CDKs, preventing the progression of the cell cycle. Two main families of CKIs exist: INK4 and CIP/KIP. INK4 inhibitors target CDK4 and CDK6, preventing the phosphorylation of retinoblastoma protein (Rb). CIP/KIP inhibitors target a broader range of CDKs, including CDK1, CDK2, and CDK4.
- **Tumor suppressor genes:** These genes encode proteins that suppress cell proliferation and promote cell cycle arrest. One well-known example is the p53 gene, which acts as a "guardian of the genome" by inducing cell cycle arrest or apoptosis in response to DNA damage.
- **DNA damage checkpoints:** These mechanisms ensure that the cell cycle is halted until DNA damage is repaired. The major DNA damage checkpoint operates in G1, preventing the cell from entering S phase before damaged DNA is repaired.
- **Other regulatory proteins:** A variety of other proteins participate in negative regulation of the cell cycle, including:
- **p21:** A CIP/KIP inhibitor that blocks the activity of CDK1 and CDK2, preventing the cell from entering S phase.
- **p16:** An INK4 inhibitor that blocks the activity of CDK4 and CDK6, preventing the phosphorylation of Rb.
- **Rb:** A tumor suppressor protein that acts as a key regulator of the G1-to-S transition. When phosphorylated by CDK4 and CDK6, Rb releases E2F transcription factors, which activate genes required for DNA replication.

The negative regulation of the cell cycle ensures that cells only divide when they are healthy and when all necessary conditions are met. This prevents uncontrolled cell proliferation, which can lead to cancer. These processes are complex and highly regulated, involving a diverse range of proteins and signaling pathways that interact in intricate ways.'
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Proteins (17)

Compounds (1,512)