Retinoblastoma gene regulates

Tumor suppressor gene types (Based on the location in the cell):*Cell surface: TGF-beta, E-cadherin*Inner plasma membrane: NF-1*Cytoplasm: NF-2, APC/beta-catenin, PTEN, SMAD 2 and SMAD 4*Nucleus: RB1, P53, WT-1, BRCA1, and BRCA2Cell cycle :*Four phases of cell cycle in the following order: G1, S, G2, and M*There are classes of proteins that stimulates or suppresses cell cycle progression from one phase to another which are CDK (Cyclin dependent kinases), Cyclins and CDK inhibitors*There are 4 CDKs (CDK1, CDK2, CDK4, CDK6) and 4 cyclins (Cyclin D, Cyclin E, Cyclin A and Cyclin B) involved in regulation of cell cycle.*2 Checkpoints in the cell cycle: G1-S checkpoint and G2-M checkpoint*Proteins that enhance cell cycle progression are CDKs which are helped by Cyclins*Proteins that cause cell cycle arrest are CDK inhibitorsFactors causing cell cycle progression at the G1-S checkpoint:uCyclinD-CDK4, CyclinD-CDK6, Cyclin E-CDK2. (Sholy D4, D6, E2)uGrowth factors (EGF, PDGF)uHyperphophorylated RB gene (E2F released from RB )Factors causing cell cycle arrest at G1-S check point:uHypophosphorylated RB (E2F binds to RB)uP53uCDK inhibitors- p15,p16,p18,p19 ( inhibits CyclinD-CDK4)uCDK inhibitors - p21,p27,p57 (inhibits both CyclinD-CDK6, CyclinE-CDK2)Factors causing cell cycle progression at the G2-M checkpoint:uCyclin B-CDK1 (B1)Factors causing cell cycle arrest at the G2-M checkpoint uCDK inhibitors - p21,p27,p57 (inhibits CyclinB-CDK1)uIonising radiationFactors causing cell cycle progression at S phase uCyclinA-CDK2 (A2)Factors causing cell cycle arrest at S phase uCDK inhibitors - p21,p27,p57 (inhibits CyclinA-CDK2) Note: D4 inhibited by p15, 16, 18 and 19 D6, E2, A2 and B1 inhibited by p21, 27 and 57.Key regulators of the cell cycle: Cyclin D, CDK4, RB, and p16.(Ref: Robbins 8/e p284-290)