Proliferation & Differentiation Flashcards
What does Erythropoietin (EPO) stimulate?
Red blood cell production
What are the four factors that can control proliferation?
- Extrinsic factors
- Tissue specific factors
- Mitogens
- Growth factors
How does EPO affect the cell cycle?
Activates the JAK/STAT pathway
What is the biological response to external signals in cell proliferation?
Change in gene expression
What is a key characteristic of highly proliferative tissues?
They include embryogenesis, skin, and intestine
What is ‘Quiescence’ in the context of cell proliferation?
A state where cells are not actively dividing
What are some diseases associated with uncontrolled cell proliferation?
- Gingival hyperplasia
- Colon cancer
- Leukemia
What is the Restriction Point in the cell cycle?
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
What triggers the rise of Cyclin D in early G1?
Mitogens induce expression of Cyclin D
What is the role of Cyclin D in the cell cycle?
It binds Cdk4/6 to form an active complex
What happens when Cyclin D-Cdk4/6 phosphorylates Rb?
Rb lets go of E2F
What does activated E2F drive the synthesis of?
Cyclin E
What is the relationship between Cyclin E and Cdk2?
Cyclin E activates Cdk2
Cdk2 phosphorylates Rb
How does the surge in Cyclin E levels affect the cell cycle?
It drives the G1/S transition
What is the effect of mitogens on the cell cycle?
They bind receptors and activate RAS-MAPK signalling pathways
What are the different types of external factors that regulate proliferation?
- Mitogens
- Growth factors
- Survival factors
- Differentiation factors
What is the significance of positive feedback in the cell cycle?
It amplifies the rise in Cyclin E levels, driving entry into S-phase
What is the role of Paneth cells in the small intestine?
They secrete Wnt signals that induce Cyclin D in stem cells
What happens to precursor cells after they migrate out of the crypt?
They stop proliferating and differentiate
What are embryonic stem cells characterized by?
Pluripotency, the potential to give rise to all cells in the adult organism
Fill in the blank: The burst in Cdk2-Cyclin E activity triggers _______.
[DNA synthesis]
True or False: Growth and proliferation are necessarily the same thing.
False
What are the learning objectives regarding cell signaling mentioned in the lecture?
- Basics of cell signaling
- Basics of transcription and translation
- Basics of Cdks & Cyclins
What are mitogens?
Stimulate proliferation by driving the cell cycle
What are growth factors?
Stimulate growth
What are survival factors?
Suppress apoptosis (death pathways)
What are differentiation factors?
Control cell lineage = what subtype a cell will become
What does the restriction point mark?
The hand over from Cdk4/6 to Cdk2 driven by the rise in cyclin E
How do mitogens induce the expression of Cyclin D?
- 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
How does E2F drive its own synthesis?
Binds to its own promoter and stimulates more synthesis of E2F
Describe the process of activating cyclin E
- Mitogens bind their cognate receptors and activate RAS-MAPK signalling pathways = activates specific transcription factors
- This drives expression of the cyclin D gene, giving rise to new cyclin D proteins which binds and activates Cdk4/6
- Active Cdk4/6-cyclin D complexes then phosphorylate Rb, causing it to let go of a transcription factor E2F
- Activated E2F drives the expression of the cyclin E gene, giving rise to new cyclin E protein which binds and activates Cdk2
- Positive feedback occurs where active Cdk2-cyclin E also phosphorylates Rb = surge in cyclin E levels
- The burst in Cdk2-cyclin E activity drives entry into S phase e.g. by phosphorylating replication origins thus triggering DNA synthesis
