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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-1107

Görlach, A; Camenisch, G; Kvietikova, I; Vogt, L; Wenger, R H; Gassmann, M (2000). Efficient translation of mouse hypoxia-inducible factor-1alpha under normoxic and hypoxic conditions. Biochimica et Biophysica Acta, 1493(1-2):125-134.

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Abstract

The heterodimeric hypoxia-inducible factor-1 (HIF-1), consisting of the subunits HIF-1alpha and HIF-1beta/ARNT, is a master transcriptional regulator of oxygen homeostasis. Under hypoxic conditions, HIF-1alpha levels very rapidly increase, mostly due to protein stabilization. However, translational regulation of HIF-1alpha has not been directly analyzed so far. Mouse HIF-1alpha exists as two mRNA isoforms (termed mHIF-1alphaI.1 and mHIF-1alphaI. 2) containing structurally different 5'-termini which might modulate translation initiation. Whereas the in vitro translation efficiency of these two mRNA isoforms was about equal, the mHIF-1alphaI.2 5'-untranslated region (5'-UTR) conferred significantly higher in vivo luciferase reporter gene activity than the mHIF-1alphaI.1 5'-UTR. Similar corresponding luciferase mRNA levels indicate translational rather than transcriptional alterations. Reporter gene expression was not affected upon exposure of transiently transfected cells to hypoxia (1% oxygen). Direct assessment of translational regulation by polysomal profile analysis of HeLaS3 cells showed that HIF-1alpha (and to a lower extent ARNT) mRNA was found mainly in the translationally active polyribosomal fractions under both normoxic and hypoxic conditions. In contrast, the association of mRNAs for beta-actin and ribosomal protein L28 with the polyribosomal fractions was substantially reduced under hypoxic conditions, suggesting decreased overall protein synthesis. Thus, efficient translation of mouse HIF-1alpha in a situation where the general translation efficiency is reduced represents a prerequisite for the very rapid accumulation of HIF-1alpha protein upon exposure to hypoxia.

Item Type:Journal Article, refereed
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
DDC:570 Life sciences; biology
Language:English
Date:2000
Deposited On:11 Feb 2008 12:20
Last Modified:27 Nov 2013 17:15
Publisher:Elsevier
ISSN:0006-3002
Publisher DOI:10.1016/S0167-4781(00)00172-X
PubMed ID:10978514
Citations:Web of Science®. Times Cited: 62
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