positive regulation of cell cycle G1/S phase transition

Definition

Target type: biologicalprocess

Any signaling pathway that activates or increases the activity of a cell cycle cyclin-dependent protein kinase to modulate the switch from G1 phase to S phase of the cell cycle. [GO_REF:0000058, GOC:mtg_cell_cycle, GOC:TermGenie]

The G1/S phase transition is a crucial checkpoint in the cell cycle, ensuring that cells only progress into DNA replication and division when appropriate conditions are met. This process is tightly regulated by a complex network of proteins and signaling pathways, and its positive regulation involves the coordinated activation of key molecular players that promote entry into S phase.

**Cyclin D and CDK4/6 activation:** The first step in positive regulation of G1/S transition involves the accumulation of cyclin D proteins. These cyclins bind to cyclin-dependent kinases 4 and 6 (CDK4/6), activating their catalytic activity. CDK4/6 phosphorylate the retinoblastoma protein (Rb), which is a key inhibitor of cell cycle progression.

**Rb phosphorylation and E2F release:** As CDK4/6 activity increases, Rb becomes progressively phosphorylated. This phosphorylation disrupts Rb's ability to bind to and inhibit transcription factors known as E2F proteins. E2F proteins are essential for the transcription of genes required for DNA replication and cell cycle progression.

**E2F activation and gene expression:** Upon release from Rb, E2F proteins become active and stimulate the expression of genes encoding components of the DNA replication machinery, including DNA polymerases, helicases, and other proteins necessary for S phase entry.

**Cyclin E and CDK2 activation:** The expression of E2F target genes also includes genes encoding cyclin E. Cyclin E binds to CDK2, activating its kinase activity. CDK2 further phosphorylates Rb and other substrates, reinforcing the signal for S phase entry.

**Other positive regulators:** In addition to the core CDK/cyclin pathway, other proteins and signaling cascades contribute to the positive regulation of G1/S transition. These include:
* **Growth factor signaling pathways:** Growth factors like epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) stimulate cell proliferation by activating downstream signaling pathways that promote cyclin D expression and CDK4/6 activity.
* **Myc oncogene:** Myc is a transcription factor that can enhance cyclin D and E expression, promoting G1/S progression.
* **PI3K/Akt pathway:** This pathway is activated by growth factors and other stimuli and can lead to the activation of CDK4/6 and the inhibition of G1-phase inhibitors like p27.

**Overall, the positive regulation of G1/S phase transition is a tightly controlled process that integrates multiple signaling pathways and molecular interactions. This intricate regulation ensures that cells only enter DNA replication and division when appropriate conditions are met, thereby preventing uncontrolled proliferation and maintaining genomic stability.**'
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Proteins (2)

Compounds (18)