PMID- 10702253
OWN - NLM
STAT- MEDLINE
DCOM- 20000403
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 10
DP  - 2000 Mar 10
TI  - Identification of alternative spliced variants of human hypoxia-inducible 
      factor-1alpha.
PG  - 6922-7
AB  - Mammalian cells are able to sense oxygen and regulate a number of genes in 
      response to hypoxia. The transcription factor Hypoxia Inducible Factor-1 (HIF-1) 
      was identified as an important key component of the hypoxia signaling pathway. 
      HIF-1 is a heterodimer composed of two members of the basic helix-loop-helix 
      transcription factor superfamily containing a PAS (PER-ARNT-SIM) domain: 
      HIF-1alpha and HIF-1beta/ARNT. During the cloning by reverse 
      transcriptase-polymerase chain reaction of the human HIF-1alpha subunit, we 
      isolated two cDNA clones which corresponded to alternative splicing of the 
      HIF-1alpha gene. Polymerase chain reaction analysis and sequencing revealed that 
      both clones possessed three additional base pairs between exons 1 and 2. Also, 
      one of them lacked 127 base pairs corresponding to exon 14. We demonstrate that 
      the mRNA of this truncated form is expressed in several human cells lines and 
      human skin but apparently not in rodents. When transfected in HEK 293 cells, the 
      corresponding 736 amino acid protein (HIF-1alpha(736)) is regulated by hypoxia in 
      a similar manner as the full-length HIF-1alpha (HIF-1alpha(FL)). In luciferase 
      transfection assays, both recombinant proteins HIF-1alpha(736) and HIF-1alpha(FL) 
      dimerize with HIF-1beta/ARNT and activate the VEGF promoter upon hypoxia. 
      However, the shorter HIF-1alpha isoform is 3-fold less active than 
      HIF-1alpha(FL), a result consistent with the lack of the C-terminal 
      transactivation domain. As expected, this small isoform can compete with the 
      endogenous and transfected full-length HIF-1alpha. Altogether, these results 
      suggest that the HIF-1alpha(736) isoform modulates gene expression upon hypoxia.
FAU - Gothie, E
AU  - Gothie E
AD  - Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, 
      Centre Antoine Lacassagne, 33 Avenue Valombrose, 06189 Nice, France. 
      gothie@unice.fr
FAU - Richard, D E
AU  - Richard DE
FAU - Berra, E
AU  - Berra E
FAU - Pages, G
AU  - Pages G
FAU - Pouyssegur, J
AU  - Pouyssegur J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Lymphokines)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
SB  - IM
MH  - *Alternative Splicing
MH  - Cell Line
MH  - DNA-Binding Proteins/*analysis/chemistry/genetics
MH  - Endothelial Growth Factors/genetics
MH  - Exons
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Lymphokines/genetics
MH  - Nuclear Proteins/*analysis/chemistry/genetics
MH  - Promoter Regions, Genetic
MH  - Protein Isoforms/analysis/chemistry/genetics
MH  - RNA, Messenger/analysis
MH  - Transcription Factors/*analysis
MH  - Transcription, Genetic
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
EDAT- 2000/03/04 00:00
MHDA- 2000/03/04 00:01
CRDT- 2000/03/04 00:00
PHST- 2000/03/04 00:00 [pubmed]
PHST- 2000/03/04 00:01 [medline]
PHST- 2000/03/04 00:00 [entrez]
AID - S0021-9258(18)30377-6 [pii]
AID - 10.1074/jbc.275.10.6922 [doi]
PST - ppublish
SO  - J Biol Chem. 2000 Mar 10;275(10):6922-7. doi: 10.1074/jbc.275.10.6922.