Fig. 1

Main parts of the biochemical regulation of the G1/S restriction point in normal (non-leukemic) cell cycle. The presence of growth factors leads to the constitutive activation of Cyclin D:Cdk4,6 complexes, which in turn favors the hypo-phosphorylation of retinoblastoma protein (pRb) in early G1 phase. The hypo-phosphorylated pRb maintains the ability to inhibit E2F transcription factors. Growth factors also stimulate the metabolic machinery of the cell, leading its mass to gradually grow. When cell growth reaches a critical threshold, the Cyclin E:Cdk2 and Cyclin A:Cdk1,2 complexes are activated resulting in hyper-phosphorylation of pRb in late G1 phase (where the differentiation potential is lost), liberation of E2F transcription factors and increased Cyclin A (and Cyclin E, E2F) expression, whose levels are indicative of the passage to the S-phase