positive regulation of G1/S transition of mitotic cell cycle

Definition

Target type: biologicalprocess

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

The G1/S transition, a critical checkpoint in the cell cycle, marks the commitment of a cell to undergo DNA replication and division. Positive regulation of this transition ensures proper progression through the cell cycle and prevents uncontrolled cell proliferation. This intricate process involves a complex interplay of signaling pathways, transcription factors, and regulatory proteins.

**Key Players and Mechanisms:**

* **Cyclin D and CDK4/6:** These proteins form a complex that phosphorylates the retinoblastoma protein (Rb).
* **Rb:** This protein acts as a tumor suppressor, inhibiting the transcription of genes required for DNA replication. Phosphorylation of Rb by cyclin D/CDK4/6 releases its inhibition, allowing G1/S transition.
* **E2F Transcription Factors:** These factors are bound and inactivated by Rb. Upon Rb phosphorylation, E2F is released and activates genes necessary for DNA replication and cell cycle progression.
* **Growth Factor Signaling:** External signals like growth factors activate signaling pathways that lead to the production of cyclin D and the activation of CDK4/6.
* **Cell Size and Nutrient Availability:** These factors also contribute to G1/S progression. Cells need to reach a certain size and have sufficient nutrients before they can enter S phase.
* **DNA Damage Checkpoints:** In the presence of DNA damage, the cell cycle is arrested at G1/S. Proteins like p53 and ATM/ATR play a role in this checkpoint control.

**Steps in Positive Regulation:**

1. **Growth Factor Stimulation:** Growth factors bind to their receptors on the cell surface, triggering a cascade of events leading to the activation of intracellular signaling pathways.
2. **Cyclin D Production and CDK4/6 Activation:** The activated signaling pathways promote the production of cyclin D and the activation of CDK4/6.
3. **Rb Phosphorylation and E2F Activation:** The cyclin D/CDK4/6 complex phosphorylates Rb, causing its release from E2F transcription factors.
4. **Gene Transcription for DNA Replication:** Activated E2F transcription factors bind to DNA and initiate the transcription of genes required for DNA replication, including DNA polymerases, helicase, and other essential proteins.
5. **Cell Cycle Progression:** With the expression of these genes, the cell is primed for DNA replication and the transition to S phase.

**Conclusion:**

The positive regulation of G1/S transition is a tightly controlled process involving multiple proteins, signaling pathways, and checkpoints. This regulation ensures proper cell cycle progression, prevents uncontrolled cell proliferation, and maintains genomic stability.'
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Proteins (20)

Compounds (1,176)