Cell growth and proliferation Flashcards
How do normal cells respond to the body needing them?
They divide when needed
Give examples of when cell proliferation is needed
Tissue maintenance Embryogenesis Repairing wounds Adapting to the environment Fighting infection
What happens when cell proliferation controls are lost?
Cancer
Do all cells in the body have the ability to divide?
No
What are stem cells?
Present in small numbers in tissues
Responsible for re-seeding proliferating precursor cells which differentiate to replace dying cells to maintain the tissue
Give an example of stem cells
Intestinal stem cells
Found in the intestinal crypt
Cells divide in the proliferation zone and move out of the crypt
Cells die by apoptosis and are replaced
What stimulates cell proliferation?
Mitogenic signals
Growth factors
What is the equation for cell proliferation?
Cell growth + cell division
Define cell growth
Increase in cell size
Increase in cytoplasmic organelles
Define cell division
Chromosome duplication
Mitosis
Cytokinesis
What happens in interphase?
G1, S and G2
Cell grows
Nuclear DNA duplicated
What happens in mitosis and cytokinesis?
Nucleus and cytoplasm divide to form two daughter cells
What regulates the cell cycle?
Cyclin-dependent kinases
Describe a cyclin dependent kinase
Cyclin binds to, and activates, cyclin-dependent kinase
What do cyclin dependent kinases do?
Phosphorylate proteins that are important during specific cell cycle phases
What regulates the different phases of the cell cycle?
Different cyclin-CDK dimers e.g. G1/S-Cdk S-Cdk M-Cdk
Which subunits are generally present throughout?
Cdk catalytic subunits 1,2,4,6
Which subunits have fluctuating levels?
Cyclin regulatory subunits
A,B,D,E
What is essential in the cell cycle?
Increase the cell size and cytoplasmic organelles Overcome restriction point Replicate the chromosomes once Fully duplicate the chromosomes Separate the duplicated chromosomes Separate the two daughter cells
What is the restriction point in G1?
The R point is a checkpoint through which cells can only progress if appropriately stimulated by mitogens
What is needed to get through the restriction point?
Mitogenic growth factor signalling
What do mitogenic growth factors signal for?
Transcription factors of immediate early genes
What do the immediate early genes code for?
Transcription of cyclinD which binds to Cdk 4 or 6 to form G1-Cdk
What does G1-Cdk do?
Binds to the retinoblastoma protein to enable progression through the R point
What is require to inactivate pRb?
G1-Cdk and G1/S-Cdk
What does pRb repress?
Transcription of cell cycle genes
Binds to E2F
Prevents transcription of genes for Cyclin E and A
How do the cyclin dependent kinases inactive pRb?
By phosphorylation
What triggers the replication of chromosomes in the S phase?
S-Cdk
What is the G2 checkpoint?
Cells cannot enter mitosis until they have completely replicated their chromosomes in S phase
What is inactive until the S phase has been completed?
M-Cdk
What is required for entry into mitosis?
M-Cdk activation
How is M-Cdk inactivated and activated?
Inactived by Wee1
Phosphorylation
This stops once all chromosomes have been replicated
What are the four stages of mitosis?
Prophase
Metaphase
Anaphase
Telophase
What happens in prophase?
Chromosome condensation
Nuclear envelope breakdown
Spindle formation and connection to kinetochores
What happens in metaphase?
Chromosomes align between two spindle poles
What happens in anaphase?
Chromosome separation
What happens in telophase?
Nuclear envelope reformation
Chromosome decondensation
What is the kinetochore?
Forms from the central region of the chromatids known as the centromere
Where mitotic spindles attach
Where do mitotic spindles form from?
Two spindle poles outside of the nucleus
When will chromosome separation occur?
In anaphase
Once all kinetochores are attached to spindle poles by mitotic spindles
What prevents the onset of anaphase?
Chromosomes with an unattached kinetochore send out a stop signal
What is the anaphase promoting complex?
When all kinetochores are attached
What results from the anaphase promoting complex?
Destruction of proteins holding sister chromatids together
How does cytokinesis occur?
A cleavage furrow forms by the action of a contractile ring
Contracts further to separate the daughter cells
What is aneuploidy?
Altered chromosome number
What does DNA damage activate?
P53
A tumour suppressor protein
What does p53 induce?
p21
A Cdk inhibitor
What does p21 do?
Inhibits G1/S-Cdk, S-Cdk, M-Cdk
Cell cycle cannot pass through checkpoints
Damaged DNA is not replicated
When is apoptosis necessary?
In development
(Fingers and toes)
When cells are no longer required
When cells are damaged
What are the stages of apoptosis?
Initiatior caspases
Executioner caspases
Cell breaks up into membrane bound fragments called apoptotic bodies
Dead cells are removed by phagocytosis
How is apoptosis different from necrosis?
Necrosis provokes an inflammatory response
What are caspases?
Enzymes required for apoptosis
Activated by death stimuli
How are caspases activated?
Inactive form is procaspases
Cleaved of pro domains and combined
What do initiator caspases activate?
Executioner caspases
What do executioner caspases do?
Degrade nuclear and cytosolic proteins
What avoids apoptosis?
Survival signals from neighbouring cells
