Tutorial 1: Cell cycle

Question 1

What stimulates hepatocyte proliferation after damage by alcohol, hepatitis viral infection or partial hepatectomy?

Answer 1

Hepatocyte growth factor (HGF) and epidermal growth factor (EGF) that activate Tyrosine Kinase receptors

Question 2

How do tyrosine kinase-mediated signals trigger cell cycle entry from G0 in mammalian cells (e.g. regenerating the liver)?

Answer 2

Progression through phases is controlled by cyclical activation of Cdk protein kinases

Cdks activate gene transcription (partly by retinoblastoma gene pRb)

Question 3

How is the cyclical activation of the Cdks via pRb proteins achieved?

Answer 3

pRb bound to E2F (inactive)
pRb is PHOSPHORYLATED by Cdk4/6-cyclinD
Releases E2F which acts as a transcription factor that upregulates transcription of cyclins required for cell cycle (i.e. cyclin E)