© 2002 AAAS
Normoxia prompts two negative regulatory hydroxylation events on the transcription factor HIF-1α: Prolyl hydroxylation in the oxygen dependent domain and asparagyl hydroxylation in the C-terminal transactivation domain. (Reprinted from R.K. Bruick, S.L. McKnight,
Like Sting's omnipresent voyeur, specialized mechanisms in the cells of higher organisms carefully monitor oxygen intake. A decrease in molecular oxygen levels (hypoxia) triggers a cascade of responses in mammalian cells, upregulating genes involved in the production of new blood vessels and red blood cells, for example. These responses are mediated by the hypoxia-inducible transcription factors (HIFs), a family of proteins containing two subunits, HIF-α and HIF-β. Under normoxic conditions, the α subunit is degraded and inactive, but when hypoxia sets in it becomes stable and active.
A revelation about HIF regulation came in 2000, when ...