regulation of G1 to G0 transition

Definition

Target type: biologicalprocess

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

The G1 to G0 transition is a critical regulatory step in the cell cycle, determining whether a cell continues to proliferate or enters a quiescent state. This transition is tightly controlled by a complex network of signaling pathways and regulatory proteins that respond to various internal and external cues.

**Key Regulatory Mechanisms:**

* **Growth Factor Signaling:** Growth factors, such as epidermal growth factor (EGF) and platelet-derived growth factor (PDGF), stimulate cell proliferation by activating signaling pathways that promote G1 progression. These pathways involve the activation of cyclin-dependent kinases (CDKs), particularly CDK4/6, which phosphorylate the retinoblastoma protein (Rb).
* **Rb Phosphorylation and E2F Release:** Phosphorylation of Rb by CDK4/6 leads to its inactivation, releasing the transcription factor E2F. E2F then activates the transcription of genes required for DNA synthesis and cell cycle progression.
* **Cyclin D1 and CDK4/6 Activation:** The expression of cyclin D1, a crucial regulatory protein for G1 progression, is stimulated by growth factor signaling. Cyclin D1 binds to CDK4/6, activating their kinase activity.
* **p53 and p21 Regulation:** The tumor suppressor protein p53 plays a crucial role in G1 arrest in response to DNA damage or other stress signals. p53 activates the expression of p21, a CDK inhibitor, which blocks the activity of CDK4/6 and prevents Rb phosphorylation.
* **Cellular Energy Levels:** The availability of sufficient ATP and other cellular resources is essential for G1 progression. Sensors of cellular energy levels, such as AMP-activated protein kinase (AMPK), can induce G1 arrest if energy levels are low.
* **Nutrient Availability:** Adequate nutrients, such as amino acids, are required for cell growth and division. Nutrient deprivation can trigger signaling pathways that inhibit G1 progression.
* **Cellular Density:** In some tissues, cell density can regulate G1 progression. Contact inhibition, a phenomenon where cells stop dividing upon reaching a certain density, can contribute to G1 arrest.
* **Hypoxia:** Low oxygen levels (hypoxia) can induce G1 arrest through the activation of hypoxia-inducible factor (HIF).

**Entry into G0:**

When cells receive signals indicating unfavorable conditions, such as growth factor withdrawal, DNA damage, or nutrient depletion, they exit the cell cycle and enter the G0 phase. This transition involves the deactivation of CDK4/6, dephosphorylation of Rb, and suppression of E2F activity. Cells in G0 are metabolically active but do not proliferate.

**Exiting G0:**

Cells in G0 can re-enter the cell cycle and progress through G1 in response to appropriate stimuli, such as growth factors or improved environmental conditions. This involves reactivation of CDK4/6, Rb phosphorylation, and E2F activation.

**Significance of G1-G0 Regulation:**

The regulation of G1-G0 transition is essential for maintaining tissue homeostasis, responding to environmental cues, and preventing uncontrolled cell proliferation. Dysregulation of this process can contribute to various diseases, including cancer.'
"

Proteins (1)

Compounds (2)