Cyclin D-CDK4

Definition

Cyclin D-CDK4 is a protein complex that plays a crucial role in regulating the cell cycle, specifically in the transition from the G1 phase to the S phase. This complex is formed when cyclin D binds to cyclin-dependent kinase 4 (CDK4), which activates CDK4's kinase activity. The cyclin D-CDK4 complex phosphorylates target proteins that promote cell cycle progression, linking growth signals to the cell's ability to divide and replicate.

5 Must Know Facts For Your Next Test

1. Cyclin D-CDK4 is activated in response to growth factors, signaling the cell to prepare for DNA synthesis.
2. Dysregulation of cyclin D-CDK4 can lead to uncontrolled cell proliferation and is often associated with various cancers.
3. Cyclin D levels fluctuate throughout the cell cycle; they increase during G1 and decrease as cells progress through S phase.
4. In addition to phosphorylating RB protein, cyclin D-CDK4 also influences other proteins that regulate gene expression related to cell growth.
5. The activity of cyclin D-CDK4 is tightly controlled by various inhibitors, such as p16INK4a, which can prevent inappropriate cell cycle entry.

Review Questions

• How does the activation of cyclin D-CDK4 contribute to the progression of the cell cycle?
  • Activation of cyclin D-CDK4 is essential for transitioning from the G1 phase to the S phase of the cell cycle. When cyclin D binds to CDK4, it activates the kinase activity of CDK4, allowing it to phosphorylate target proteins. This phosphorylation leads to the inactivation of RB protein and the release of transcription factors that promote DNA synthesis, thus pushing the cell toward replication.
• Discuss the implications of cyclin D-CDK4 dysregulation in cancer development.
  • Dysregulation of cyclin D-CDK4 is a significant factor in cancer development, as it can lead to unchecked cell proliferation. In many cancers, mutations or overexpression of cyclin D or CDK4 result in increased kinase activity, bypassing normal regulatory mechanisms. This abnormal activation can disable tumor suppressor pathways, particularly those involving RB protein, leading to uncontrolled growth and potential tumor formation.
• Evaluate the role of cyclin D-CDK4 in cellular responses to external growth signals and its potential as a therapeutic target in cancer treatment.
  • Cyclin D-CDK4 plays a pivotal role in how cells respond to external growth signals by integrating those signals into pathways that promote cell cycle progression. Targeting this complex with specific inhibitors offers a promising therapeutic strategy in cancer treatment. By inhibiting cyclin D-CDK4 activity, it may be possible to slow down or halt the proliferation of cancer cells that have become reliant on this pathway for growth, thus providing a more effective approach to managing certain malignancies.

Related terms

Cell Cycle: The series of events that a cell goes through as it grows and divides, including phases G1, S, G2, and M.

Cyclins:

A family of proteins that regulate the cell cycle by activating cyclin-dependent kinases (CDKs) through binding.

RB Protein: Retinoblastoma protein, a key regulator of the cell cycle that inhibits progression from G1 to S phase by binding to transcription factors.