Figure 2

Proposed oxygen-sensing mechanisms for the regulation of gene transcription and the involvement of HIF-1 as a hypoxia-mediated transcription factor. See main text for further details. The thick 'down' arrows indicate a reduction in the amount of the molecule shown. [AQ18] CO might affect oxygen sensing by locking the sensor (shown as Oxy/De-oxy in the plasma membrane and the inset) in an oxy conformation. Co²⁺/Ni²⁺ might affect oxygen sensing by locking the sensor in a de-oxy conformation. AA, arachidonic acid; ARNT, aryl hydrocarbon receptor nuclear translocator; CREB, cAMP-responsive element binding protein; CBP, CREB-binding protein; DAG, diacyl glycerol; ECF, extracellular fluid; HIF-1, hypoxia-inducible factor-1; ICF, intracellular fluid; IP₃, inositol triphosphate; MAPK, mitogen-activated protein kinase; O₂ ^-•, superoxide anion; P, phosphorylation; PKC, protein kinase C; ROS, reactive oxygen species; SAPK, stress-activated protein kinase; T_0.5, half-life.