Fig. 1

Assumed simplified mechanisms for the effects of hypoxia on cell cycle commitment. Hypoxia varies the active amount of Hif1α and Hif2α proteins, through which cell cycle regulating proteins are regulated. The variation in cell cycle regulators positively (cyclin D, cyclin E, Myc) or negatively (p21/p27 and Rb) controls the downstream protein level of E2F. The progression of cell cycle G1-phase into S-phase commitment is controlled by the accumulation of E2F protein exceeding a set threshold level. Different biological interactions are shown in the figure