MAKAP compartmentalizes oxygen-dependent control of HIF-1α

Wei Wong, April S. Goehring, Michael S Kapiloff, Lorene K. Langeberg, John D. Scott

Research output: Contribution to journalArticle

39 Citations (Scopus)

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 languageEnglish
JournalScience Signaling
Volume1
Issue number51
DOIs
StatePublished - Dec 23 2008

Fingerprint

Hypoxia-Inducible Factor 1
Oxygen
Muscle
Phosphotransferases
Muscles
Ubiquitin-Protein Ligases
Ubiquitin
Cardiac Myocytes
Protein Kinases
Transcriptional Activation
Machinery
Proteins
Transcription Factors
Stabilization
Genes
Chemical activation
Enzymes
Experiments

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Wong, W., Goehring, A. S., Kapiloff, M. S., Langeberg, L. K., & Scott, J. D. (2008). MAKAP compartmentalizes oxygen-dependent control of HIF-1α. Science Signaling, 1(51). https://doi.org/10.1126/scisignal.2000026

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 journalArticle

Wong, W, Goehring, AS, Kapiloff, MS, Langeberg, LK & Scott, JD 2008, 'MAKAP compartmentalizes oxygen-dependent control of HIF-1α', Science Signaling, vol. 1, no. 51. https://doi.org/10.1126/scisignal.2000026
Wong W, Goehring AS, Kapiloff MS, Langeberg LK, Scott JD. MAKAP compartmentalizes oxygen-dependent control of HIF-1α. Science Signaling. 2008 Dec 23;1(51). https://doi.org/10.1126/scisignal.2000026
Wong, Wei ; Goehring, April S. ; Kapiloff, Michael S ; Langeberg, Lorene K. ; Scott, John D. / MAKAP compartmentalizes oxygen-dependent control of HIF-1α. In: Science Signaling. 2008 ; Vol. 1, No. 51.
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