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Sci. Signal., 23 December 2008
Vol. 1, Issue 51, p. ra18
[DOI: 10.1126/scisignal.2000026]

RESEARCH

Editor's Summary

Anchor’s a Way to Regulate HIF-1{alpha}
Under conditions in which oxygen concentrations are normal (normoxia), the transcription factor hypoxia-inducible factor 1{alpha} (HIF-1{alpha}) is ubiquitinated and undergoes proteasome-dependent degradation. When oxygen becomes scarce (hypoxia), such as occurs in tumors and during myocardial infarction, HIF-1{alpha} is no longer degraded; it forms a heterodimer with the constitutively expressed HIF-1β subunit and induces the expression of hypoxia-associated genes. The products of these genes, including proteins such as vascular endothelial growth factor and glucose transporter 1, help the cell to adapt to conditions of low oxygen concentration. Wong et al. now provide evidence that the scaffolding protein muscle A kinase–anchoring protein (mAKAP), best known for its role in organizing protein kinase A and other signaling molecules, binds to HIF-1{alpha} and components of the ubiquitin machinery to regulate the stability of HIF-1{alpha} in a bidirectional fashion. Under normoxia, components of the mAKAP complex target HIF-1{alpha} for degradation; under hypoxia, however, mAKAP organizes factors that stabilize HIF-1{alpha}. In addition, the perinuclear localization of mAKAP is required to position HIF-1{alpha} close to its target genes. Together, these results suggest that mAKAP functions as an important regulatory component of the hypoxic response in cardiomyocytes.

Citation: W. Wong, A. S. Goehring, M. S. Kapiloff, L. K. Langeberg, J. D. Scott, mAKAP Compartmentalizes Oxygen-Dependent Control of HIF-1{alpha}. Sci. Signal. 1, ra18 (2008).

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