Proliferation & Differentiation

Question 1

What does Erythropoietin (EPO) stimulate?

Answer 1

Red blood cell production

Question 2

What are the four factors that can control proliferation?

Answer 2

• Extrinsic factors
• Tissue specific factors
• Mitogens
• Growth factors

Question 3

How does EPO affect the cell cycle?

Answer 3

Activates the JAK/STAT pathway

Question 4

What is the biological response to external signals in cell proliferation?

Answer 4

Change in gene expression

Question 5

What is a key characteristic of highly proliferative tissues?

Answer 5

They include embryogenesis, skin, and intestine

Question 6

What is ‘Quiescence’ in the context of cell proliferation?

Answer 6

A state where cells are not actively dividing

Question 7

What are some diseases associated with uncontrolled cell proliferation?

Answer 7

• Gingival hyperplasia
• Colon cancer
• Leukemia

Question 8

What is the Restriction Point in the cell cycle?

Answer 8

A point of no return beyond which cells no longer need mitogens to continue the cycle

This is towards the end of the G1 phase

Question 9

What triggers the rise of Cyclin D in early G1?

Answer 9

Mitogens induce expression of Cyclin D

Question 10

What is the role of Cyclin D in the cell cycle?

Answer 10

It binds Cdk4/6 to form an active complex

Question 11

What happens when Cyclin D-Cdk4/6 phosphorylates Rb?

Answer 11

Rb lets go of E2F

Question 12

What does activated E2F drive the synthesis of?

Answer 12

Cyclin E

Question 13

What is the relationship between Cyclin E and Cdk2?

Answer 13

Cyclin E activates Cdk2

Cdk2 phosphorylates Rb

Question 14

How does the surge in Cyclin E levels affect the cell cycle?

Answer 14

It drives the G1/S transition

Question 15

What is the effect of mitogens on the cell cycle?

Answer 15

They bind receptors and activate RAS-MAPK signalling pathways

Question 16

What are the different types of external factors that regulate proliferation?

Answer 16

• Mitogens
• Growth factors
• Survival factors
• Differentiation factors

Question 17

What is the significance of positive feedback in the cell cycle?

Answer 17

It amplifies the rise in Cyclin E levels, driving entry into S-phase

Question 18

What is the role of Paneth cells in the small intestine?

Answer 18

They secrete Wnt signals that induce Cyclin D in stem cells

Question 19

What happens to precursor cells after they migrate out of the crypt?

Answer 19

They stop proliferating and differentiate

Question 20

What are embryonic stem cells characterized by?

Answer 20

Pluripotency, the potential to give rise to all cells in the adult organism

Question 21

Fill in the blank: The burst in Cdk2-Cyclin E activity triggers _______.

Answer 21

[DNA synthesis]

Question 22

True or False: Growth and proliferation are necessarily the same thing.

Answer 22

False

Question 23

What are the learning objectives regarding cell signaling mentioned in the lecture?

Answer 23

• Basics of cell signaling
• Basics of transcription and translation
• Basics of Cdks & Cyclins

Question 24

What are mitogens?

Answer 24

Stimulate proliferation by driving the cell cycle

Question 25

What are growth factors?

Answer 25

Stimulate growth

Question 26

What are survival factors?

Answer 26

Suppress apoptosis (death pathways)

Question 27

What are differentiation factors?

Answer 27

Control cell lineage = what subtype a cell will become

Question 28

What does the restriction point mark?

Answer 28

The hand over from Cdk4/6 to Cdk2 driven by the rise in cyclin E

Question 29

How do mitogens induce the expression of Cyclin D?

Answer 29

- Mitogens activate RTKs which then activate RAS GTPase which activates the MAP kinase pathway - MAPK pathway controls transcription factors involved in the transcription and translation of cyclin D protein - Cyclin D forms a complex with cdk4/6 to become active

Question 30

How does E2F drive its own synthesis?

Answer 30

Binds to its own promoter and stimulates more synthesis of E2F

Question 31

Describe the process of activating cyclin E

Answer 31

1. Mitogens bind their cognate receptors and activate RAS-MAPK signalling pathways = activates specific transcription factors 2. This drives expression of the cyclin D gene, giving rise to new cyclin D proteins which binds and activates Cdk4/6 3. Active Cdk4/6-cyclin D complexes then phosphorylate Rb, causing it to let go of a transcription factor E2F 4. Activated E2F drives the expression of the cyclin E gene, giving rise to new cyclin E protein which binds and activates Cdk2 5. Positive feedback occurs where active Cdk2-cyclin E also phosphorylates Rb = surge in cyclin E levels 6. The burst in Cdk2-cyclin E activity drives entry into S phase e.g. by phosphorylating replication origins thus triggering DNA synthesis