negative regulation of G1 to G0 transition

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of G1 to G0 transition. [GO_REF:0000058, GOC:di, GOC:TermGenie, PMID:24088570]

The G1 to G0 transition, also known as cell cycle arrest, is a critical regulatory point that prevents cells from entering the cell cycle and dividing uncontrollably. Negative regulation of this transition involves a complex interplay of signaling pathways and protein complexes that act to suppress the expression of genes required for cell cycle progression.

Key players in this process include:

* **Cyclin-dependent kinases (CDKs)**: These enzymes are crucial for regulating the cell cycle. In the context of G1 to G0 transition, CDKs are typically inactive, preventing the phosphorylation of downstream targets necessary for cell cycle progression.
* **CDK inhibitors (CKIs)**: These proteins bind to and inhibit CDKs, further preventing their activation. Key CKIs involved in G1 to G0 transition include p21, p27, and p57.
* **Transcription factors**: These proteins regulate gene expression. For example, the transcription factor E2F is a key regulator of genes required for cell cycle entry. During G1 to G0 transition, E2F activity is repressed, preventing the expression of these genes.
* **Signaling pathways**: Various signaling pathways can trigger G1 to G0 transition. Examples include:
* **TGF-β signaling**: This pathway promotes the expression of CKIs, leading to CDK inhibition and cell cycle arrest.
* **p53 signaling**: This pathway is activated in response to DNA damage and stress. It promotes the expression of p21, a CKI that inhibits CDK activity and arrests the cell cycle.
* **Hippo signaling**: This pathway regulates organ size and cell proliferation. Activation of the Hippo pathway can lead to G1 to G0 transition.

The interplay of these factors leads to a cascade of events that ultimately prevent the cell from entering the cell cycle. These events include:

* **Reduced expression of cell cycle promoting proteins**: The expression of proteins like cyclins and CDKs, which are essential for cell cycle progression, is downregulated.
* **Increased expression of cell cycle inhibitors**: The expression of CKIs like p21, p27, and p57 is upregulated, inhibiting CDK activity.
* **Repression of E2F activity**: E2F is a transcription factor that promotes the expression of genes required for cell cycle entry. Its activity is suppressed during G1 to G0 transition, preventing the expression of these genes.

These events ultimately lead to cell cycle arrest, preventing cells from dividing uncontrollably. Negative regulation of G1 to G0 transition is essential for maintaining tissue homeostasis, preventing uncontrolled proliferation, and responding to stress or damage. Dysregulation of this process can contribute to various diseases, including cancer.'
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Proteins (1)

Compounds (1,824)