cell cycle tutorial

Question 1

cell cycle overview

Answer 1

growth factor eg EGF causes dimerization, which causes auto-phosphorylation, recruiting adapter/accessory proteins eg GRB2

RAS is inactive (has GDP), and is phosphorylated by RAS activating protein (eg SOS) into active RAS (RasA) ((with GTP)- does this by converting ANOTHER GTP to GDP

RasA activates Kinase 1 (MAPKKK), which phosphorylates kinase 2 (MAPKK- has 1 phosphate), which phosphorylates kinase 3 (MAPK- has 2phosphates)- one kinase phosphorylates another kinase by converting ATP to ADP: MAPKKK= Raf, MAPKK= MEK, MAPK= ERK

ERK goes from cytoplasm to nucleus to turn on genes, which activates Myc, which causes a domino effect of CDK’s- Myc protein produces cyclin D, which binds CDK4/6

E2F is a TF bound to Rb (active form of RB)- CDK complex phosphorylates Rb so that E2F no longer bound to Rb (inactive), and E2F activates cyclin E transcription- as one conc of complex goes down, it triggers another one (again through E2F)

Question 2

other sites that are phosphorylates

Answer 2

once dimer formed, PI3K kinase phosphorylates, which phosphorylates PIP 2 to PIP3- this causes PDK1 to activate PKB/AKT- this phosphorylates FOXO (TF) in nucleus, which goes in cytoplasm and CANNOT produces things (eg P27/KIP1) that reduce cell cycle proteins and produce APOPTOTIC protein- FOXO normally produces these inhibitor proteins

BCL 2 is anti-apoptotic: this is associated with BAD, which inactivates BCL2: AKT phosphorylates BAD, inhibiting it, so BCL 2 is free to do its stuff

caspase 9 is apoptotic, and is inactivated by AKT through phosphorylation

thus phosphorylation causes inhibition of the proteins

once liver regenerated ie cell cycles completed, P10 inhibits PIP2 to 3, so less AKT etc

Question 3

oncogenes and TMS

Answer 3

P10 and RB are mutated (normally TMS), or cmyc, cyclin D, Ras, Raf are mutated and become oncongenes