Mechanisms Of Disease 1

Question 1

Define cell growth

Answer 1

A bigger organism would need more cells

Question 2

Define differentiation

Answer 2

Cells become complex and usually there’s a end to growth
A program of cell type-specific gene expression
Cell morphology and function changes

Question 3

What are 3 main groups of diseases related to cell growth and differentiation?

Answer 3

Developmental conditions
- can be cell growth or differentiation
- eg. Neural tube defects like spina bifida

Neoplasia
- cancer and tumours

Others
- eg. Cardio hypertrophy

Question 4

What the two main forms of cell growth?

Answer 4

Hypertrophy - bigger cells
Hyperplasia - more cells (most common)

Controlled by cell death

Question 5

What is hypertrophy?

Answer 5

• cells grow bigger
• more proteins, more membrane etc
• elevated protein synthesis is a big driver of increased cell size

Question 6

How is cell growth and differentiation governed?

Answer 6

• intracellular signals and extracellular signals
• signals converge on the promoters of key genes
• promoters act as “coincidence detectors”

Question 7

What is paracrine signalling?

Answer 7

Produced locally to stimulate proliferation of a different cell type that has the appropriate cell surface receptor

Question 8

What is autocrine signalling?

Answer 8

Produced by a cell that also expresses the appropriate cell surface receptor

Question 9

What is endocrine signalling?

Answer 9

Conventional hormones, released systemically for distant effects.

Question 10

What are mitogens?

Answer 10

Proteins that stimulate and promote survival
Eg. Growth factors and interleukins (EGF, FGF, NGF, IL2, IL4)

Question 11

What is the function of TGF(beta)?

Answer 11

Induce differentiation and inhibit proliferation

Question 12

Describe and name the phases of the cell cycle

Answer 12

M phase - cells divide by mitosis
G1- has diploid number of chromosomes
S phase - DNA replication
G2 - tetraploid chromosomes

Question 13

What is the G0 phase of the cell cycle?

Answer 13

Cells that have left the cell cycle are in this phase
Quiescent cells undergo terminal differentiation

Question 14

How can FACS be used to analyse cell DNA content?

Answer 14

• if DNA stain is applied
• FACS machine can measure the DNA content of every cell in a population
• Data is used to plot a graph
• if the rate of division is high the number of cells in each stage of the cell cycle should be closer in proximity

Question 15

How can fluorescent microscopy be used to observe the stages of the cell cycle?

Answer 15

The fluorescent stains allow us to see the cells.
Blue = DNA
Red = Y-Tubulidentata
Green = CHEK2
Yellow = centrioles

Question 16

What are cell cycle checkpoints?

Answer 16

Controls involving protein kinases and phosphatase to ensure the strict alteration of mitosis and DNA replication.

Question 17

What is the checkpoint between G1 and S phase?

Answer 17

Restriction point
- DNA not damaged
- cell size big enough
- metabolite/nutrient stores

Question 18

What checkpoint occurs between G2 and M phase?

Answer 18

• DNA completely replicated
• DNA not damaged

Question 19

What is the checkpoint during mitosis?

Answer 19

Position of chromosomes aligned on spindle

Question 20

What is CDK?

Answer 20

Catalytic subunit
10 genes

Question 21

What is cyclin?

Answer 21

Regulatory subunit
> 20 genes
Expression induced by growth factors

Question 22

What happens when cyclin binds to CDK?

Answer 22

Active cyclin-CDK complex forms
Phosphorylates specific substrates

Question 23

How is cyclin-CDK activity regulated?

Answer 23

• cycles of synthesis (gene expression) and destruction (by proteasome)
• post translational modifications by phosphorylation
• Dephosphorylation
• binding of cyclin-dependent kinase inhibitors (CDKIs)

Question 24

What is retinoblastoma (RB) protein?

Answer 24

A key substrate of cyclin-dependent kinases of G1 and G1/s

Question 25

How does RB usually function?

Answer 25

Unphosphorylated RB binds to E2F transcription factor

Preventing its stimulation of S-phase protein expression

But in the presence of Cyclin D-CDK4 + Cyclin E-CDK2

RB gets phosphorylated and detaches from E2F

Allowing E2F to stimulate the expression of more cyclin E (positive feedback) and S-phase proteins

Question 26

What 3 things occur when DNA damage is detected?

Answer 26

Stop the cell cycle (by expression of cyclin dependent kinase inhibitors)

Attempt DNA repair (nucleotide or base excision enzymes, mismatch repair)

Programmed cell death (BCL2 family, caspases)

Question 27

What is the role of TP53 or P53?

Answer 27

In cells with healthy DNA TP53 is destroyed by proteasome and there would be barley any of it in the cell.

In damaged DNA cells kinases are activated which phosphorylate TP53.

Phosphorylated TP53 expresses CDKI where it will cause cell cycle arrest. It also leads to DNA repair.

If repair isn’t possible apoptosis occurs.

Question 28

How can mutations in TP53 cause cancer?

Answer 28

• prevent cell cycle arrest (FASTER GROWTH)
• prevent apoptosis (DO NOT DIE)
• prevent DNA repair (MORE MUTATIONS)

Question 29

What are chemotherapeutic drugs?

Answer 29

Drugs that act on the cell cycle
Objective: stop proliferation, induce apoptosis
eg. S-phase drugs and M-phase drugs

Question 30

What are ways S-phase drugs can cause DNA damage?

Answer 30

• 5-flurouracil (PREVENTS SYNTHESIS IF THYMIDINE)
• Cisplatin. (BINDS TO DNA CAUSING DAMAGE OR BLOCK REPAIR)

Question 31

What are 2 examples of M-Phase drugs?

Answer 31

Vinca alkaloids and paclitaxel (Taxol)

Question 32

What is the function of Vinca Alchaloids?

Answer 32

• stabilise free Tubulin
• prevent microtubule polymerisation
• arrest cells in mitosis

Question 33

What is the function of Palcitaxel (Taxol) drugs?

Answer 33

• stabilises microtubules
• preventing de-polymerisation
• arrests cell in mitosis