Quiescence and Senescence Flashcards
What is free living cell growth regulated by?
What about cell growth in multicellular animals?
Environmental cues e.g. nutrient supply
Extracellular signals
What is apoptosis?
Programmed cell death
- avoids further damage to surrounding cells + tissues
What is necrosis?
Unplanned cell death
- response to damage/infection
- can cause further damage to surrounding cells + tissues
Why are the cell cycle checkpoints needed?
i.e. what are the bad things that could happen in each stage?
G1 - DNA damage
- unfavourable extracellular environment
S - incomplete replication
G2 - insufficient cell growth
M - chromosome incorrectly attached to mitotic spindle
What regulates the cell cycle checkpoints?
Cyclin/CDK complexes
How are cyclin/CDK complexes dynamic?
CDK = present throughout cell cycle
Regulatory cyclins oscillate between synthesised state + destructed state
What happens when S-cyclin binds to CDK?
What happens when M-cyclin binds to CDK?
At G1/S checkpoint
-> triggers DNA replication machinery
At G2/M checkpoint
-> triggers mitosis machinery
What does a peak in CDK activity result from?
What happens at this point?
What happens after this?
Steady accumulation of cyclin
Mitosis occurs
Rapid destruction of cyclin
-> decrease in M-CDK activity
= interphase
Explain how cyclin accumulates
- Inhibitory kinase (Wee1) phosphorylates cyclin
= keeps it inactive - Activating phosphatase (Cdc25)removes inhibitory phosphates
- Active cylinder/CDL phosphorylates Cdc25
(+ve feedback)
How can you identify mutants that have passed through the cell cycle too quickly?
V small
Explain how cyclin levels decrease
APC (anaphase promoting complex) adds chains of ubiquitin molecules to cyclin proteins
= tags them for rapid destruction at proteosomes
What does the G1/S phase checkpoint prevent?
Replication of damaged DNA
How does the G1/S checkpoint prevent replication of damaged DNA?
- X-rays damage DNA
- Activates protein kinases
-> phosphorylate + activate p53 - p53 acts as a TF
-> binds to regulatory region of p21 gene - p21 transcribed + translated
- p21 binds to CDK complexes
= inactivates them - Allows time for cell to repair damaged DNA or undergo apoptosis
What are the 2 roles of p53?
Transcription factor
Tumour suppressor
What happens if there is no DNA damage?
p53 is degraded in proteosomes
What happens in cell cycle withdrawal?
Cells instructed to exit cell cycle and…:
> undergo apoptosis
> enter G0
How are cells instructed to enter G0?
Absence of proliferation signals
Presence of -ve regulators
What is quiescence?
Cells in G0 phase but have the capacity to re-enter the cell cycle when appropriate
How does Rb control cell proliferation in resting cells?
Rb sequesters TFs essential for initiating DNA replication + nucleotide metabolism at the start of S phase
How does Rb control cell proliferation in proliferating cells?
Mitogen signals simulate synthesis of G1 cyclin
-> active G1/S cyclin/CDK complex accumulates
- > phosphorylates Rb
- > alters Rb conformation
- > promotes release of TFs that promotes initiation of S phase
- > cell proliferation
What are the 2 roles of mitogen signals in cell proliferation?
> Promote cyclin synthesis
> Promote degradation of kinase inhibitory proteins e.g. Cdc25
What are terminally differentiated cells?
Give examples
Specialised cells unable to proliferate
Neurons
Keratinocytes in skin
Goblet + enterocytes
What is senescence?
Which cells evade this?
What are they known as?
Cells that have lost the capacity to proliferate
- can only divide a finite no. of times
Cancer cells
Immortalised/Transformed
What are the contributing factors to senescence?
> accumulation of KIPs/CIPs w/ successive divisions
> shortening of telomeres
