3 - Cyclins & Cdks Intro Flashcards
Describe the development of a malignant tumour?
A tumour first grows duue to uncontrollable cell proliferation. This is followed by the gain of more mutations which attain the ten hallmarks of cancer including the metastatic phenotype, where the cell can spread, adhere to new surfaces and proliferate.
What is the cell cycle restriction checkpoint?
A checkpoint in G1 where the cell either continue growing if conditions are correct, or enter G0, quiescence.
What are the master regulators of the cell cycle?
Cdk/Cyclin complexes
How were Cdks/Cyclins discovered?
Fission yeast & Xenopus oocytes
Structural changes are imposed on Cdks when cyclins bind. Describe this?
When cyclins bind the Cdk’s PSTAIRE/activation loop moves, and ATP is reorientated. This exposes residues for phosphorylation. T14 & Y15 = inhibitory phosphorylation, activating phosphorylation is on the activation loop
Cyclins are what kind of activator?
Allosteric
Which Cdk-cyclin complexes regulate which stages of mitosis?
G1 - Cdk4/6, Cyclin D; S - Cdk 2, Cyclin E & Cdk2, Cyclin A; G2 Cdk1, Cyclin A & Cdk1, Cyclin B
Who identified in yeast the network of genes required for mitotic entry
Lee Hartwell, Paul Nurse
Wee 1 is a
Kinase
Cdc25 is a
Phosphatase
Cdc2 is a
Kinase/Cdk
Cdc 13 is a
Cyclin
Cdks-cyclin complexes are phosphorylated at the activating residue by?
CAK; Cdk activating protein
The pattern of expression of Cyclins was defined by Tim Hunt in Sea Urchins. What was this?
Cyclins are periodically expressed and destroyed throughout the cell cycle
How are cyclins degraded?
They are degraded by ubiquitin ligase, which in the case of Cyclin is APC/C. This polyubiquinates cyclins for recognitions and destruction by proteasomes
