L13- Control of proliferation and differentiation

Question 1

What are the different cyclin/cdk complexes?

Answer 1

M-phase cyclin/cdk
G1-phase cyclin/cdk
G1/s-phase cyclin/cdk
S-phase cyclin/cdk

Question 2

What are all the cyclin/cdk complexes regulated by?

Answer 2

Cyclin synthesis/degradation

Phosphorylation of the cdk subunit

Question 3

If there is no signal to enter cell cycle what does the cell do?

Answer 3

Enters phase G0

Question 4

Which cells spend most of their life in G0?

Answer 4

Neurones and muscle cells

Question 5

What determines cell division rate? (eg liver cells divide once a year, gut stem cells twice a day)

Answer 5

Variation in time spent in G1 or G0

Question 6

What needs to be present after division to enter G1?

Answer 6

Stimulus- growth factor, enough nutrients/atp

Question 7

What’s checked at the G1 checkpoint?

Answer 7

Enough nutrients? Growth factor present? Is cell big enough? Is DNA undamaged?
If these are all yes- ENTER S PHASE, replicate DNA

Question 8

If there isnt enough growth facot, nutrients, if the cell isnt big enough or DNA damaged what does the cell do?

Answer 8

It remains in G1 until it’s fixed. Doesn’t enter S phase

Question 9

What’s checked at G2 checkpoint?

Answer 9

Is Dna replicated?
Is cell big enough?
Is DNA undamaged
If all are yes- couples S phase to M phase— mitotic spindle assembles.

Question 10

How is the cell cycle stopped?

Answer 10

Inhibitor proteins stopping cyclin/cdk complexes

Question 11

How does p53 stop the cell cycle entering S phase?

Answer 11

In the absence of DNA damage p53 is degraded.
If DNA is damaged it activates p21 (activated transcription of p21) which is a cdk inhibitor protein. This binds onto the cyclin/cdk complex and makes it inactive.
Can’t enter S phase.

Question 12

How does DNA damage affect M-Cdk?

Answer 12

It inhibits activating phosphatase (cdc25) so M-Cdk isn’t activated. It can’t enter the cell cycle.

Question 13

What are the mechanisms at the checkpoints?

Answer 13

G1-S- Cdk inhibitors block entry to S phase

G2-M- INhibition of activating phosphatases (cdc25) blocks entry to mitosis

M-G1- Inhibition of APC activation delays exit from mitosis

Question 14

What’s the difference between growth and proliferation?

Answer 14

Growth- cell gets bigger

Proliferation- cells divide, needs growth or cells would get smaller.

Question 15

What are the 3 functions of growth factors?

Answer 15

1. Growth factors to stimulate cell growth
2. Mitogens to stimulate cell division
3. survival factors to promote cell survival, by suppressing apoptosis.

Question 16

Most growth factors stimulate many cell types. Which one doesn’t?

Answer 16

Erythropoeitin- only has receptors on red blood cells

Question 17

How do mitogenic growth factors stimulate cell proliferation?

Answer 17

Growth factors bind to receptor-> causes intracellular signalling pathway–> increases protein synthesis and decreases protein degradation.
So there’s no Rb. Cell cycle enters S phase

Question 18

What is Rb?

Answer 18

Retinoblastoma protein. Rb suppresses transcription. proteins needed for S-phase are not made. Cells cannot enter S phase.

Growth factors phosphorylate Rb. Rb present when there’s no mitogenic growth factor,

Question 19

What is myostatin an example of?

Answer 19

A growth inhibitor protein. Inhibits Cdk in muscle growth and proliferation. Mutation in myostatin causes super muscly cows etc.
Some growth factors inhibit proliferation by activating cdk inhibitor proteins..

Question 20

In summary what are S phase and G1 phase cyclin/cdk complexes regulated by?

Answer 20

• Phosphorylation
• Cyclin synthesis/degradation
• Inhibitor proteins

Question 21

What does p53 do in summary?

Answer 21

Arrests the cell in G1 upon DNA damage

Question 22

What are growth factors needed for?

Answer 22

Mammalian cell growth (can be division, growth or survival)

Question 23

What do growth factors lead to?

Answer 23

Activation of G phase cyclin/cdks, which phosphorylate Rb, leading to transcription of genes needed for S phase

Question 24

What do mitogenic growth factors do?

Answer 24

Increase cell number