Oxygen sensing and the activation of the hypoxia inducible factor 1 (HIF-1)--invited article.

For mammals, oxygen sensing is fundamental to survive. An adequate response to reduced oxygen tension, herein termed hypoxia, requires an instantaneous adaptation of the respiratory and the circulatory systems. While the glomus caroticum as well as the pulmonary and systemic vasculature and potentially also the airway chemoreceptors enable a corresponding response within seconds, changes in gene expression require minutes to hours. Hypoxia-induced gene expression depends on the activation of several transcription factors. Hypoxia-inducible factor-1 (HIF-1) has been identified as the key transcription factor complex that coordinates gene expression during hypoxia. To understand how abundance and activation of HIF-1 is regulated is of fundamental importance as it may open new therapeutic avenues to treat ischemic diseases or cancer where HIF-1 appears to be a key component of the pathophysiology.