The heterodimeric HIF (hypoxia-inducible factor)-1 is a transcriptional master regulator of several genes involved in mammalian oxygen homoeostasis. Besides the well described regulation of the HIF-1α subunit via hydroxylation-mediated protein stability in hypoxia, there are several indications of an additional translational control of the HIF-1α mRNA, especially after growth factor stimulation. We identified an interaction of CPEB (cytoplasmic polyadenylation-element-binding protein) 1 and CPEB2 with the 3′-UTR (untranslated region) of HIF-1α mRNA. Overexpression of CPEB1 and CPEB2 affected HIF-1α protein levels mediated by the 3′-UTR of HIF-1α mRNA. Stimulation of neuroblastoma SK-N-MC cells with insulin and thus activation of endogenous CPEBs increased the expression of a luciferase reporter gene fused to the 3′-UTR of HIF-1α as well as endogenous HIF-1α protein levels. This could be abrogated by treating the cells with CPEB1 or CPEB2 siRNAs (short interfering RNAs). Injection of HIF-1α cRNA into Xenopus oocytes verified the elongation of the poly(A)+ (polyadenylated) tail by cytoplasmic polyadenylation. Thus CPEB1 and CPEB2 are involved in the regulation of HIF-1α following insulin stimulation.
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Research Article|
December 12 2008
Cytoplasmic polyadenylation-element-binding protein (CPEB)1 and 2 bind to the HIF-1α mRNA 3′-UTR and modulate HIF-1α protein expression
Sonja Hägele;
Sonja Hägele
*Department of Cardiovascular Physiology, Georg-August University Göttingen, Humboldtallee 23, D-37073, Göttingen, Germany
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Uwe Kühn;
Uwe Kühn
†Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes Str. 3, D-06120 Halle, Germany
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Melanie Böning;
Melanie Böning
*Department of Cardiovascular Physiology, Georg-August University Göttingen, Humboldtallee 23, D-37073, Göttingen, Germany
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Dörthe M. Katschinski
Dörthe M. Katschinski
1
*Department of Cardiovascular Physiology, Georg-August University Göttingen, Humboldtallee 23, D-37073, Göttingen, Germany
1To whom correspondence should be addressed (email katschinski@physiol.med.uni-goettingen.de).
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Publisher: Portland Press Ltd
Received:
July 03 2008
Revision Received:
August 22 2008
Accepted:
August 27 2008
Accepted Manuscript online:
August 27 2008
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem J (2009) 417 (1): 235–246.
Article history
Received:
July 03 2008
Revision Received:
August 22 2008
Accepted:
August 27 2008
Accepted Manuscript online:
August 27 2008
Citation
Sonja Hägele, Uwe Kühn, Melanie Böning, Dörthe M. Katschinski; Cytoplasmic polyadenylation-element-binding protein (CPEB)1 and 2 bind to the HIF-1α mRNA 3′-UTR and modulate HIF-1α protein expression. Biochem J 1 January 2009; 417 (1): 235–246. doi: https://doi.org/10.1042/BJ20081353
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