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 Signaljournal_title
Science signalingauthors
Wong W,Goehring AS,Kapiloff MS,Langeberg LK,Scott JDdoi
10.1126/scisignal.2000026subject
Has Abstractpub_date
2008-12-23 00:00:00pages
ra18issue
51eissn
1945-0877issn
1937-9145pii
1/51/ra18journal_volume
1pub_type
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