<prompt> Retinoblastoma gene regulatesG1-S phaseG2- M phaseG0 - S phaseS- G2 phase  <response>: Tumor suppressor gene types Based on the location in the cell:Cell surface: TGF-beta, E-cadherinInner plasma membrane: NF-1Cytoplasm: NF-2, APCbeta-catenin, PTEN, SMAD 2 and SMAD 4Nucleus: RB1, P53, WT-1, BRCA1, and BRCA2Cell cycle :Four phases of cell cycle in the following order: G1, S, G2, and MThere 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 inhibitorsThere 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 checkpointProteins that enhance cell cycle progression are CDKs which are helped by CyclinsProteins 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, E2uGrowth factors EGF, PDGFuHyperphophorylated RB gene E2F released from RB Factors causing cell cycle arrest at G1-S check point:uHypophosphorylated RB E2F binds to RBuP53uCDK inhibitors- p15,p16,p18,p19 inhibits CyclinD-CDK4uCDK inhibitors - p21,p27,p57 inhibits both CyclinD-CDK6, CyclinE-CDK2Factors causing cell cycle progression at the G2-M checkpoint:uCyclin B-CDK1 B1Factors causing cell cycle arrest at the G2-M checkpoint uCDK inhibitors - p21,p27,p57 inhibits CyclinB-CDK1uIonising radiationFactors causing cell cycle progression at S phase uCyclinA-CDK2 A2Factors 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 8e p284-290 