26 - Cell cycle regulation

How retinoblastoma protein blocks passage through G₁/S

E2F is a transcription factor that promotes the transcription of S-phase genes. Retinoblastoma protein block E2F from binding to the promoter region

How cyclin-CDK complexes control the G₁/S checkpoint

A signalling molecule, such as epidermal growth factor, binds to its receptor activating it and causing a cascade of reactions which result in increased cyclin D levels. Cyclin D binds and activates CDK which phosphorylates retinoblastoma protein on serine and threonine residues. The phosphorylated blastoma is no longer able to bind E2F and diffuses away allowing E2F to bind to the promoter region

E2F also promotes the transcription of positive regulators which increase cyclin-CDK complex activity (positive feedback) and G₂/M cyclins

G₂/M cyclins lead to degradation of the G₁/S cyclins (negative feedback)

The characteristics of oncogenes vs tumour suppressors

Proto-oncogenes are genes that have the potential to be mutated to oncogenes. Oncogenes code for mutated signalling proteins that cannot be regulated (always activated). Even in the absence if a proper signal the mutated signalling protein initiates cell division

Retinoblastoma and p53 are a tumour suppressors. Mutations in these can cause unregulated cell proliferation.

How p53 stop damaged cells dividing

Proteins detect damaged DNA and send signals to p53 and it is activated. p53 is a transcription factor that promotes the transcription of of p21. p21 binds to the cyclin-CDK complex and inhibits it. This pauses the cell cycle until DNA damage is repaired. If the damaged DNA cannot be repaired than p53 can stimulate apoptosis