Abstract
The activity of the transcription factor hypoxia-inducible factor 1α (HIF-1α) is increased in response to reduced intracellular oxygen. Enzymes of the protein ubiquitin machinery that signal the destruction or stabilization of HIF-1α 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- 1α 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-1α 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.
| Original language | English |
|---|---|
| Journal | Science Signaling |
| Volume | 1 |
| Issue number | 51 |
| DOIs | |
| State | Published - Dec 23 2008 |
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ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
- Medicine(all)
Cite this
MAKAP compartmentalizes oxygen-dependent control of HIF-1α. / Wong, Wei; Goehring, April S.; Kapiloff, Michael S; Langeberg, Lorene K.; Scott, John D.
In: Science Signaling, Vol. 1, No. 51, 23.12.2008.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MAKAP compartmentalizes oxygen-dependent control of HIF-1α
AU - Wong, Wei
AU - Goehring, April S.
AU - Kapiloff, Michael S
AU - Langeberg, Lorene K.
AU - Scott, John D.
PY - 2008/12/23
Y1 - 2008/12/23
N2 - The activity of the transcription factor hypoxia-inducible factor 1α (HIF-1α) is increased in response to reduced intracellular oxygen. Enzymes of the protein ubiquitin machinery that signal the destruction or stabilization of HIF-1α 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- 1α 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-1α 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.
AB - The activity of the transcription factor hypoxia-inducible factor 1α (HIF-1α) is increased in response to reduced intracellular oxygen. Enzymes of the protein ubiquitin machinery that signal the destruction or stabilization of HIF-1α 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- 1α 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-1α 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=58749099474&partnerID=8YFLogxK
U2 - 10.1126/scisignal.2000026
DO - 10.1126/scisignal.2000026
M3 - Article
C2 - 19109240
AN - SCOPUS:58749099474
VL - 1
JO - Science Signaling
JF - Science Signaling
SN - 1937-9145
IS - 51
ER -