mAKAP compartmentalizes oxygen-dependent control of HIF-1alpha.

Abstract:

:The activity of the transcription factor hypoxia-inducible factor 1alpha (HIF-1alpha) is increased in response to reduced intracellular oxygen. Enzymes of the protein ubiquitin machinery that signal the destruction or stabilization of HIF-1alpha tightly control this transcriptional response. Here, we show that muscle A kinase-anchoring protein (mAKAP) organized ubiquitin E3 ligases that managed the stability of HIF-1alpha and optimally positioned it close to its site of action inside the nucleus. Functional experiments in cardiomyocytes showed that depletion of mAKAP or disruption of its targeting to the perinuclear region altered the stability of HIF-1alpha and transcriptional activation of genes associated with hypoxia. Thus, we propose that compartmentalization of oxygen-sensitive signaling components may influence the fidelity and magnitude of the hypoxic response.

journal_name

Sci Signal

journal_title

Science signaling

authors

Wong W,Goehring AS,Kapiloff MS,Langeberg LK,Scott JD

doi

10.1126/scisignal.2000026

subject

Has Abstract

pub_date

2008-12-23 00:00:00

pages

ra18

issue

51

eissn

1945-0877

issn

1937-9145

pii

1/51/ra18

journal_volume

1

pub_type

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