Cell Cycle Regulation Flashcards
Where are the checkpoints in the cell cycle?
- R point during G1
- G1/S
- G2/M
- Metaphase/ Anaphase checkpoint
What is a cyclin?
Cyclin is a family of proteins that control the progression of cells through the cell cycle by activating cyclin-dependent kinase (CDK) enzymes.
- Cdk regulator
What is Cdk?
Cyclin-dependent kinase
What cyclin and Cdk partner is present in the growth phase?
cyclin D- Cdk 4 and Cdk6
What cyclin and Cdk partner is present in the G1 to S transition?
cyclin E- Cdk 2
What cyclin and Cdk partner is present in the S phase?
cyclin A- Cdk 2, Cdk1
What cyclin and Cdk partner is present during mitosis?
cyclin B- Cdk1
How do you activate Cdk2?
- Cdk has a T loop structure in its inactive form that blocks the active site keeping it inactive
- When cyclin is present, it binds to Cdk, changes the conformation of the T-loop and exposes the active site
- this enables ATP to bind
- becomes partially active - Cdk activator kinase phosphorylates the t-loop area
- this fuly activates Cdk
- now can fully bind to its substrate
When does mitogen-independent late G1 growth start?
- After mitogen-dependent early G1
- when cell goes past the point of no return
- hyperphosphorylation and inactivation of the retinoblastoma tumour suppressor protein (pRb)
- stimulating signals cyclin E & Cdk2
What is the Rb/E2F pathway in cell cycle regulation?
- happens during the R point
1. Rb protein is phosphorylated to a low level - dependent on cdk 4 and 6 and cyclin B - prevents activation of transcription factors E2F and DP
2. Once passes R point, another Cdk cyclin kicks in - Cdk 2 becomes activated when bound to cyclin E
- Once complex comes in, this further phosphorylates Rb
3. Hyper phosphorylation of Rb occurs - Rb becomes inactivated
- Transcription factors E2F/DP can be activated
- Turns on transcription of the genes required for the S phase
- Further activation of cyclin E to move the cell cycle forward
What happens during the G1/S cell cycle check point?
- DNA integrity needs to be checked before DNA replication
- controlled by CDK2 and cyclin A
- p53 pathway
What happens during the p53 pathway?
- double and single stranded DNA break
- Once p53 is activated, it acts on p21 (a Cdk inhibitor)
- Regulates cycle by controlling the cyclin/cdk complexes such as the Cyclin E/Cdk2 complex
- Can either inhibit the complex, therefore G1 arrest occurs as pRB will inhibit the transcription factors
- Or will allow the complex to form, thereby hyper phosphorylating Rb and letting the pathway lead to DNA synthesis
What inhibits p53/ promotes p53 degradation?
MDM2
What happens during the G2/M cell cycle check point?
- assess DNA integrity
- controlled by Cdk1 and Cyclin B
- p53 pathway
Which proteins remove and add inhibitory phosphates to Cdk?
Cdc25a: - phosphatase - removes inhibitory phosphates from Cdk2 Wee1: - kinase - adds inhibitory phosphate onto Cdk1
