HIF-1 and HIF-2: working alone or together in hypoxia?
Peter J. Ratcliffe
Peter J. Ratcliffe
View: Text | PDF
Commentary

HIF-1 and HIF-2: working alone or together in hypoxia?

Abstract

Erythropoietin (EPO) is the hormonal regulator of red cell production and provided the paradigm for oxygen-regulated gene expression that led to the discovery of hypoxia-inducible factor (HIF). In this issue of the JCI, Rankin and colleagues show, using targeted gene inactivation, that induction of Epo expression in murine liver is dependent on the integrity of HIF-2α, and not HIF-1α (see the related article beginning on page 1068). These results demonstrate distinct functions for different HIF-α isoforms that could potentially be exploited in therapeutic approaches to anemia.

Authors

Peter J. Ratcliffe

×

Figure 1

HIF activity under hypoxic and normoxic conditions.

Options: View larger image (or click on image) Download as PowerPoint
HIF activity under hypoxic and normoxic conditions. In normoxia, hydroxy...
In normoxia, hydroxylation at 2 proline residues promotes HIF-α association with pVHL and HIF-α destruction via the ubiquitin/proteasome pathway, while hydroxylation of an asparagine residue blocks association with coactivators. In hypoxia, these processes are suppressed, allowing HIF-α subunits (both HIF-1α and HIF-2α) to escape proteolysis, dimerize with HIF-1β, recruit coactivators, and activate transcription via HREs. N, asparagine; P, proline; OH, hydroxyl group; Ub, ubiquitin.