Lecture 20: Controlling proliferation and differentiation Flashcards
What is erythropoietin?
Secreted cytokine that stimulates red blood cell production
What are mitogens as an external factor?
Stimulate proliferation by driving the cell cycle
What are growth factors as an external factor?
Stimulate growth
What are survival factors as an external factor?
Suppress apoptosis
What are differentiation factors as an external factor?
Control cell lineage
What is marked by R in the cell cycle?
The restriction point Cells no longer need mitogens Handover from Cdk4/6 to Cdk2 driven by rise of Cyclin E
What is the overall process of mitogens triggering cell cycle entry?
- Mitogens bind bind to receptors and activate RAS-MAPK signalling pathways and turn on transcription factors
- Expression of cyclin D gene and Cyclin D protein activates Cdk4/6
- The complex phosphorylates Rb to let go of E2F
- E2F drives Cyclin E expression which activates Cdk2
- Positive feedback where cdk2-cyclin E phosphorylates Rb and Cyclin E increases
- Drives entry into S phase
What is the process of proliferation restriction?
Restricted in the base of the crypt 1. Paneth cells secrete Wnt signals 2. Stem cells induce cyclin D and proliferate 3. Precursor cells migrate out of crypt away from Wnt signals 4. When out of range they stop proliferating and differentiate