Carcinogenesis
uncontrolled cell growth and cell spreading
Hyperplasia
cells resemble those in normal tissue
Dysplasia
cells are cytologically abnormal
Cancer
malignant tumours
Cdks
cyclin dependent kinases
~ protein kinases that phosphorylate specific serine/threonine residues
Cyclin D
G1 cyclin
activates Cdk4 or CDK6
Cyclin E
G1/S cyclin
activates Cdk2
Cyclin A
S cyclin
activates Cdk2
Cyclin B
M cycline
activate Cdk1
Each cyclin-cdk complex activates…
~ events in their cell cycle phase
~ cyclin-cdk in the next cell phase e.g. by promoting expression
Name the mechanisms used to regulate Cdk activity
when bound to cyclin, the Cdk active site becomes unburied (active) and available to bind to
activation - phosphorylation of a threonine residue by cdk-activating kinases (CAK)
~ occurs after cyclin binding
phosphorylation inactivates cdk by blocking ATP binding site controlled by: Wee1 kinase (G1, S, G2) Cdc25 phosphatase (G2) ~ creates a positive feedback loop
Two types:
~ bind to cyclin-cdk complex - distorts structure and prevents ATP binding
~ bind to cdk only - alter the structure and prevent binding with cyclin