PMID- 10978514
OWN - NLM
STAT- MEDLINE
DCOM- 20001207
LR  - 20190610
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1493
IP  - 1-2
DP  - 2000 Sep 7
TI  - Efficient translation of mouse hypoxia-inducible factor-1alpha under normoxic and 
      hypoxic conditions.
PG  - 125-34
AB  - 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.
FAU - Gorlach, A
AU  - Gorlach A
AD  - Institute of Physiology, University of Zurich-Irchel, Winterthurerstrasse 190, 
      CH-8057 Zurich, Switzerland.
FAU - Camenisch, G
AU  - Camenisch G
FAU - Kvietikova, I
AU  - Kvietikova I
FAU - Vogt, L
AU  - Vogt L
FAU - Wenger, R H
AU  - Wenger RH
FAU - Gassmann, M
AU  - Gassmann M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (ARNT protein, human)
RN  - 0 (Arnt protein, mouse)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Transcription Factors)
RN  - 138391-32-9 (Aryl Hydrocarbon Receptor Nuclear Translocator)
SB  - IM
MH  - Animals
MH  - Aryl Hydrocarbon Receptor Nuclear Translocator
MH  - Cell Hypoxia
MH  - DNA-Binding Proteins/*biosynthesis/chemistry/genetics
MH  - Dimerization
MH  - Exons
MH  - Gene Expression Regulation
MH  - Genes, Reporter
MH  - HeLa Cells
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Mice
MH  - Nuclear Proteins/*biosynthesis/genetics
MH  - Plasmids
MH  - Protein Biosynthesis
MH  - Protein Isoforms/biosynthesis/genetics
MH  - RNA, Messenger/biosynthesis
MH  - *Receptors, Aryl Hydrocarbon
MH  - Transcription Factors/genetics
MH  - Transfection
EDAT- 2000/09/09 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/09/09 11:00
PHST- 2000/09/09 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/09/09 11:00 [entrez]
AID - S0167-4781(00)00172-X [pii]
AID - 10.1016/s0167-4781(00)00172-x [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2000 Sep 7;1493(1-2):125-34. doi: 
      10.1016/s0167-4781(00)00172-x.