Melanoma Molecular Maps Projects



Title: Cell cycle key regulators
Legend: Cell cycle progression is driven by the sequential activation/inactivation of cyclin dependent kinases (CDK), which are active when bound to regulatory proteins (cyclins). If complexed with cyclin D, CDK drive entry into the cell cycle by phosphorylating the retinoblastoma protein (RB), which causes the release of the E2F family of transcription factors, allowing progression from G1 to S phase. This process is negatively regulated by CDK inhibitors (CDKI) and is also under control at a number of checkpoints found in at least four stages: G1, G1/S transition, G2/M transition and at the metaphase/anaphase transition. p53 (the "genome guardian") is one of the most important cell cycle proteins. Under normal circumstances p53 is dormant until activated by DNA damage. p53 then activates the p21 protein to arrest the cell cycle in G1 to allow DNA repair or to induce apoptosis if the DNA damage is too severe. APAF1 (apoptotic peptidase activating factor 1, CED4); ATM (ataxia telangiectasia mutated, TELO1); BAX (BCL2-associated X protein); Cdc25 (cell division cycle 25 C, CDC25C); CDK1 (cyclin dependent kinase 1, Cdc2); CDK2; CDK4; CDK6; CHK1, CHK2 (checkpoint kinase 1, -2); Cyclin A; Cyclin B; Cyclin D; Cyclin E; DNA-PK (DNA damage induced protein kinase, a heterodimer of the PRKDC and G22P1 gene products); E2F1 (belongs to the E2F family of transcription factors); FOXO1 (forkhead box class O [FOXO]member 1, FKHR); GADD45 (growth arrest and DNA damage inducible alpha, GADD45A); HDM2 (human homolog of mouse double minute 2 [MDM2]); mTOR (mammalian target of rapamycin); p14 (ARF, p14 alternative reading frame, one of the two products of the CDKN2A locus); p16 (p16INK4A, one of the two products of the CDKN2A locus); p21 (CDKN1A, CDK inhibitor 1A, CIP1, WAF1); p27 (CDK inhibitor 1B, KIP1); PCNA (proliferating cell nuclear antigen); PLK1 (polo like kinase 1); Proteasome (multiprotein organelle); Puma (p53 upregulated modulator of apoptosis; BCL2 binding component 3 [BBC3]); RB (retinoblastoma protein, pRB, RB1); SGK (serum/glucocorticoid regulated kinase 1). Figure #38
Author: The MMMP Team (updated: August 2008)

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