Cell cycle regulation Flashcards
What is a CDK? What other protein is required to bind to it for activity?
Cyclin- dependent kinases
- family of protein kinases
Activity of the kinase activity is cyclical (regulates the proteins that carry out cyclical cellular functions)
Are heavily regulated
Require binding to a cyclin for activity
Stable protein levels across cell cycle
How many CDK’s and cyclins do animals have?
Animals have 8 CDK’s and 10 cyclins
The activity of CDKs cycles with the cell cycle
The activity of cyclins cycles with the cell cycle
What is the T loop and what does it do during regulation of CDK activity?
Phosphorylation of Thr160 in the T-loop activates the CDK by allowing target binding
Phosphorylation of Tyr15, near the amino terminus, inactivates CDK2 by blocking the ATP binding site with its negatively charged
It’s important that they all become active
Car at a traffic light - you keep the engine running but you have your foot on the break (phosphorylation of Tyr15) - they can all be activated very quickly when required and it is much faster
First you get the phosphorylation of Tyr15 but it blocks the ATP binding site, still inactive (break analogy)
- phosphorylation of Thr160 - T loop and removal of Tyr15 phosphoryl group activates cyclin-CDK manifold (the engine is ready but the break is on)
- phosphatase (remove the Tyr15 so takes the brake off - you now get activation of the CDK)
- phosphorylates targets
- phosphorylates the phosphatase that is removing the Tyr15 (more and more of the molecules become active) - feedback loop that is positive - takes the break off all the CDK’s
- phosphorylate the DBRP - triggers the degradation of the cyclin (add ubiquiton)
Big peak of activity and then it drops
CDK won’t become activated until the next round
What is the importance of the destruction box? What recognises this sequence and what happens to it?
9 amino acid sequence near the amino terminus
Ubiquitous - small protein covalently attached to proteins as a markers of degradation (or can be signalling something else)
Proteasome - large protein complex that degrades proteins back into amino acids
does the binding of p21 activate or inhibit the activity of CDK?
Inhibitors
Give three examples of target proteins of CDK’s. Which phase of the cell cycle is phosphorylated and what happens when it is?
Mitosis - nuclear lamins
- the lamins are phosphorylated (that breaks down the mesh structure)
- causes the lamins to be repulsed
- breakdown of the nuclear envelope (so the chromosomes can be accessed)
- the nuclear envelope then reforms
Mitosis - condensins
- lock around the DNA
- responsible for condensing the DNA
G1 to S checkpoint release
The CDK will be inhibited until the damage is repaired (inhibited by p21)
What is the role of the protein RB?
The RB protein is a tumour suppressor which plays a vital role in the negative control of the cell cycle and in tumour progression
What is a checkpoint?
One of several points in the cell cycle at which the progression of a cell to the next stage can be halted until conditions are favourable.
- Start of G1, G2 and M
What is Knudon’s two hit hypothesis?
Rare autosomal disease in which cancers forms in retinal cells in both eyes - the retinoblasts fail to differentiate - cells contribute to dive and form tumours
Hypothesises that cancer is the result of accumulated mutations to a cells DNA
Hereditary - have a higher chance of developing cancer due to already having a hit when they are born
Non-hereditary - have a lower chance
What controls this orderly process?
- protein protein interaction
- protein phosphorylation
- protein degradation
- protein synthesis
