Cell cycle: Revision session topics Flashcards
What are Mitogens?
Proteins which binds to a receptor which tells it to be poliferated
growth stimulate to initiate cell cycle and the upregulation of Cyclin D
How do you tell a cell to poliferate?
Must induce cell cycle progression
1) What is the first step in upregulation of Cycline D? (cell cycle)
Mitogen (ligand) binds to the receptor, causing conformational change and autophosphorylation on the tyrosine kinase
2) What happens to the receptor when autophosphorylated?
Receptor binds to the adaptor protein on the SH2 domain with a phosphate
3) What happens to the SH2 adaptor protein after it binds to the receptor?
SH2 adapter protein binds to Ras-GEF (Guansine exchange factor) Exchanges GDP for GTP into RAS to activate it, leading to signalling cascade.
4) What happens to the RAS when it begins to the signalling cascade?
Since RAS is a kinase it binds to MAP (Mitogen adaptor protein) Kinase, Kinase, Kinase.
MAP KKK (Raf) is phosphorylated to MAPKK (Mek) (ATP to ADP)
MAP KK (Mek) is phosphorylated to MAPK (Erk) (ATP to ADP)
5) What happens after MAPK (Erk) is formed?
MAPK (Erk) is phosphorylated to activate multiple proteins
including transcription factors which switch on Cyclin D and Cyclin E:
C-myc, C-jun, C-fos
6) What happens to C-myc when its activated?
C-myc activates and binds to the promoter region of cyclin D gene
Cyclin D RNA produced and then coverts to Cyclin D protein production
7) Whats the first thing Cyclin D does?
Cyclin-dependent kinase 4 and 6 are always around in the cell
Binds to Cyclin D in order to activate it
Also phosphorylates RB (retinal blastoma)
8) What does Rb protein do when its phosphorylated?
Active Rb protein binds to transcription factor E2F which inhibits it
When phosphorylated by CD and CDK it is partically inactivated and release protein
9) What does the transfactor do when released?
Transfactors binds to the promoter of Cyclin E, leading to an increase in cyclin E
Cyclin E binds to CDK2
When bound completely inactivates Rb protein
E2F protein increase with Cyclin E release
10) When E2F is increased, what happens?
E2F binds to promoter of cyclin A
Cyclin A binds to CDK1 or CDK2
Triggering S-phase (DNA replication)
How do you reduce E?
When you have loads of E2F it can activate p27 by the E2F binding to p27 gene promoter
p27 inhibits cyclin e and cdk2 activety
Rb reactivates and E2F is inhibited
Any remaining cyclin E is removed by the proteosome following ubiquitination by the SCF complex
