G0 Cell Cycle Outline
Terminally differentiated cells (cell can’t proliferate, continue in cell cycle)
G1 Cell Cycle Outline
All cellular content (excluding chromosomes) are duplicated. Feeds to S
Synthesis Cell Cycle Outline
Duplication of all 46 chromosomes. Feeds to G2
G2 Cell Cycle Outline
Check DNA for damage (proliferation/termination signals). Feeds into mitosis
Effects of cell cycle pathway dysregulation
Uncontrolled proliferation of cells (cancer)
Redundant Signaling Pathways Effect
Multiple pro and anti proliferation signals. Targeting 1 signaling pathway won’t kill cancer
4 possible signals for cells to receive
Death cues, Survival cues, Proliferation cues & Growth inhibition cues
What signals do a cancer cells inherit
Survival and proliferation
Types of Extracellular Signalling
Autocrine, Paracrine & Endocrine
Pro-oncogene Outline
Non-mutated (natural/healthy) version of an oncogene
Mitogens Outline
Promotes cell Division: Inhibits anti-proliferation pathways
Growth Factors Outline
Promotes Cell Division: Stimulates protein synthesis and Inhibits protein degradation
Survival Factors Outline
Promotes Cell Survival: Suppress apoptosis
Cell Cycle Checkpoint Outline
Temporary breaks in cell cycle to assess if progress is viable (ie do we have all necessary materials in necessary amounts, is DNA damaged
Main Cancer Checkpoint
G1-S. Allows to progress to S stage despite DNA damage
Cyclins Levels in Cell Cycle
Expressed at different levels in cell cycle
Cyclin Dependent Kinase
Expressed at same levels throughout cell cycle
G1 Cyclins
Promote passage through G1 Restriction Point
G1-S Cyclins
Binds Cdks at G1 committing cell to DNA Replication
S Cyclins
Binds CdKs during S phase of DNA Replication
M Cyclins
binds Cdks to promote mitosis
CDK Catalytic Subunit Outline
Performs kinase activity when bound to cyclin
Cyclin Substrate
Regulatory subunit, that allows CDK activity when bound
E2F G->S Phase
Rb complex phosphorylated by CDK4/6 / CyclinD & releases E2F. E2F binds genome and activates enzymes for DNA synthesis