The Nobel Prize in Physiology or Medicine 2019 was awarded jointly to William G. Kaelin Jr, Sir Peter J. Ratcliffe and Gregg L. Semenza for their discoveries of how cells sense and adapt to oxygen availability. They discovered that cells employ the hydroxylation of HIF-1α, a subunit of the transcriptional factor HIF-1, to sense the cellular oxygen level, and, consequently, the unhydroxylated HIF-1α under hypoxic conditions will be rapidly accumulated and enter the nucleus to regulate the transcription of over one thousand genes. The hypoxic response is closely related to a number of human diseases, including anemia, polycythemia, cardiovascular disease, stroke, and cancer. This paper reviews the history of the discovery of the cellular hypoxic response pathway, as well as human diseases involved.
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