40. Life and Death of the Cell Flashcards
What are 3 methods of cell signalling?
Endocrine (distant target cell)
Autocrine (target on the same cell)
Paracrine (adjacent target cell)
What do mitogens do?
Stimulate cell division
Relieve intracellular controls that block cell cycle progress
What do growth factors do?
Stimulate cell growth
Promote synthesis of proteins
Inhibiting degradation
What do survival factors do?
Promote cell survival
Suppress apoptosis
What regulates transition through the cell cycle?
Cyclin-Cyclin dependent kinase complexes
What do G-1 cyclins do?
Help promote passage through the restriction point in late G1
What do G2/S cyclins do?
Bind CDKs at the end of G1 Commit the cell to DNA replication
What do S-cyclins do?
Bind CDKs during S phase
Required for the initiation of DNA replication
What do M-cyclins do?
Promote the events of mitosis
Levels of what in circulation control the cell cycle?
Cyclins fluctuate (control) Levels of CDK are steady
What is p53?
Transcription factor/ tumour suppressor
Key regulator of cell proliferation
Mutations common in cancer
What is p53 activated by?
DNA damage
What is the p53 response to DNA damage?
- Induces p21
- p21 inhibits kinase activity of cyclin-CDK complex
- Rb is not phosphorylated, stays bound to E2F
- S-phase genes aren’t turned on
- If damaged not repaired p53 remains high
- Cell undergoes cell death
What are some characteristics of apoptosis?
Affects single cells
No inflammatory response
Non-random DNA fragmentation
How is apoptosis regulated by extrinsic signals?
Cells receive signals to commit suicide from other cells
Initiated by formation of death-inducing cell surface receptor signalling complex (DISC)
Leads to activation of caspase 8
How is apoptosis regulated by intrinsic signals?
Cell senses damage and initiates its own death
Mediated by changes in mitochondrial function
Regulated by anti-apoptotic Bcl2 family members
Activates caspase 9
How are death receptors activated?
- Ligand binds
- Receptor trimerises
- Activation of pro-caspase 8
- Activates other caspases ultimately leading to apoptosis
What antagonises the anti-apoptotic effect of Bcl2?
Cytoplasmic p53
Mitochondrial outer-membrane permeabilisation
Release of Cytochrome C into cytosol
What happens why Cyt C leaks into the cytoplasm?
Binds to Apaf1
Binds to and activates caspase 9
These 3 things form the apoptosome
Apoptosome activates other caspases leading to apoptosis
What do caspases do?
DNA fragmentation by endonuclease
Loss of cell shape
Organelle breakdown
Cell fragmentation into apoptotic bodies, phagocytosed by macrophages
How can the intrinsic pathway be overridden by cancer cells?
p53 mutation
Overexpression of BCL2
