Lecture on Cyclins, Cyclin-Dependent Kinases, and Cell Cycle Control

Introduction

• Discussion on how cyclins and cyclin-dependent kinases (CDKs) control the cell cycle.
• Connection to mitogen-activated protein signaling and its role in the phosphorylation of CDKs.

Cell Cycle Phases and Checkpoints

• Cell Cycle Phases: G1, S, G2, M (presented in a linear fashion).
• Checkpoints: Critical points for decision-making where the cell is prompted to proceed based on protein signals.
• CDKs: Act as 'passports' allowing progression past checkpoints.

G1 Checkpoint

• Pre-S Phase Check: Ensures DNA is undamaged.
• Role of p53: Holds the cell at the checkpoint if DNA is damaged.
• Checks for Unfavorable Environment:
  • Cell size
  • Nutrient availability
  • Presence of mitogen
• Once past the checkpoint, the cell proceeds through the cycle or dies.

S Phase and G2 Checkpoint

• S Phase: Ensures chromosomes are faithfully duplicated and checks for damage.
• G2 Checkpoint: Ensures no damage before splitting chromosomes in mitosis.

Mitotic Checkpoint

• Metaphase Check: Ensures chromosomes are captured correctly by spindle fibers.

Responsiveness to Mitogens

• Mitogen-Responsive Phase: G1 phase.
• Restriction point: Where the cell decides to proceed based on mitogenic signals.

G0 Phase

• G0 Phase Details:
  • Cells can withdraw from the cycle into a resting state.
  • Neurons typically remain in G0.
  • Other cells may temporarily enter G0.

Cyclins and CDKs Function

• Cyclins: Control expression throughout the cycle (rise and fall in levels).
• CDKs: Constant presence, become active when bound to cyclins.
• Complex Formation:
  • Cyclins and CDKs form complexes to drive cell cycle events.
  • Different cyclins are active in different phases (e.g., Cyclin D in G1, Cyclin E at G1-S transition).

Regulation of CDKs

• Gradual Cyclin Expression: Transition requires a rapid response despite gradual cyclin increase.
• CDK Activation Steps:
  • Cyclin binding to CDK.
  • Phosphorylation: Inhibitory and activating phosphates.
  • Phosphatase removes inhibitory phosphate, activating the CDK.

Importance and Control of CDKs

• CDKs are controlled by multiple enzymes (kinase, phosphatase) due to their crucial role.
• Malfunctioning CDKs can lead to cancer (proto-oncogenes to oncogenes).

Conclusion

• Importance of CDKs and cyclins in cell cycle regulation.
• Link to cancer biology due to potential mutations leading to uncontrolled cell division.