L2 - Mechanisms of Disease: Cell growth + differentiation Flashcards
What is cell growth?
division of cells by mitosis to produce a bigger organism
What is cell differentiation?
the transition of a cell from one type to another to produce a complex, multi-function organism.
Exit from the cell cycle are called post-mitotic.
Begins to express cell-specific genes, and therefore its morphology and function changes.
Describe Hypertrophy in terms of cell growth?
When cell become bigger:
cells make more macro-molecules (proteins, more membrane etc)
Caused by elevated protein synthesis
The heart is a good example
Describe Hyperplasia in terms of cell growth?
When number of cells increases due to proliferation
Caused by the cell cycle
What signals govern cell growth and differentiation and give examples of each?
Intracellular signals - checks on cellular physiology.
Extracellular signals - growth factors and cell adhesion
Where do intracellular and extracellular signals integrate/converge?
on the promoters of key genes
Describe extracellular signalling including the 3 types?
Ligand binds to a receptor and causes intracellular cascade.
3 classes of signalling: paracrine, autocrine, and endocrine
Describe the role of extracellular signalling in cell growth and differentiation?
They are proteins that:
- stimulate proliferation and promote survival (growth factors and interleukins)
- induce differentiation and inhibit proliferation
- can do both (Wnt ligands)
- induce apoptosis (TNF family)
What are the phases of the cell cycle?
Mitosis
Interphase: G1, S, G2
What happens during Interphase of the cell cycle?
Cells grow larger in size and essential macromolecules are synthesised.
In S phase - the DNA is replicated.
What are quiescent cells and what happens to them?
They are cells that leave the mitotic phase and enter the G0 phase. They either are stagnant in this stage until they rejoin the cell cycle in G1.
Or they begin the process of differentiation - and become terminally differentiated (post-mitotic).
May go onto cell death - apoptosis.
How does the amount of DNA in the cell change throughout cell cycle?
G1 - 2N ploidy
G2 - Tetraploidy - 4N
What is FACS and what is it used for?
Flourescence activated cell sorting.
Analyses the DNA content of cells in a population.
DNA stain is applied and FACS can measure the DNA content of every cell.
How is fluorescence microscopy used to detect DNA?
Blue shows DNA
Red shows gamma tubulin
Green shows CHEK2
Yellow shows that Red and green are in the same place: centrioles.
Throughout the cell cycle the colour intensity and amount change and DNA can be measured.
What do the cell cycle checkpoints involve and what are their roles?
Specific protein kinases and phosphatases.
Kinases add phosphate groups and phosphatases remove the phosphates.
They ensure that cells have duplicated correctly before entering mitosis and that cells have proliferated correctly before entering S phase.
What is the purpose of the restriction point in the cell cycle and where is it located?
Located at the end of G1 phase.
Ensures that there is no DNA damage/errors in the DNA which would be copied in the S phase.
Also checks the nutrient/metabolite stores and the cell size.
What is the purpose the G2 checkpoint?
Located at the end of G2
Ensures that the DNA has replicated correctly and is ready for mitosis.
What is the purpose of the metaphase checkpoint?
Checks that the chromosomes have aligned on the spindle correctly
What are CDKs and how many do we have?
Cyclin-dependant kinases - important kinases involved in regulating the cell cycle.
10 genes encode for CDK catalytic subunit
More than 20 genes encode for cyclin - the regulatory subunit
What do growth factors induce the expression of and how does this help the cell cycle?
induce expression of cyclin genes, which allows it to forma complex with CDK. Active Cyclin-CDK phosphorylates substrates, which alows for progression of the cell cycle.
How is Cyclin-CDK activity regulated?
cyclin proteins have a high rate of turnover. Continuously synthesised and destroyed.
Post translational modification of cyclins can result in activation, inhibition or destruction of kinase activity.
CDKIs also bind to cyclin complexes and inhibit them.
Describe the events that occur if damage is detected in the DNA?
1) The cycle is stopped (CDK Inhibitors, CHEK2)
2) Attempt to repair the DNA damage (nucleotide or base excision, mismatch repair)
3) If repair is impossible - the cell enters apoptosis (capsases)
Explain the role of TP53?
Tumor suppressor protein 53.
Made by the cell and destroyed by the proteosome.
However when a mutagen binds to DNA and causes damage to the DNA, it activated kinases that convert TP53 TO PHOSPHORYLATED TP53, which cannot be destroyed by the proteosome.
- Expresses CKIs which cause cell cycle arrest.
- Activation of DNA repair
- Activates cell death
What are the effects of TP53 losing its function?
CANCER
- nothing to prevent cell cycle arrest - so faster growth of cells
- nothing to induce apoptosis - cells do not die
- prevents DNA repair - more mutations, more adaptation and cancer progression.
