PMID- 10446188
OWN - NLM
STAT- MEDLINE
DCOM- 19990909
LR  - 20220408
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 34
DP  - 1999 Aug 20
TI  - Identification of a hypoxia response element in the transferrin receptor gene.
PG  - 24147-52
AB  - Expression of the transferrin receptor, which mediates iron uptake from 
      transferrin, is negatively regulated post-transcriptionally by intracellular iron 
      through iron-responsive elements in the 3'-untranslated region of the transferrin 
      receptor mRNA. Transcriptional mechanisms are also involved in receptor 
      expression, but these are poorly understood. In this study we have characterized 
      the transferrin receptor promoter region and identified a functional hypoxia 
      response element that contains a binding site for hypoxia-inducible factor-1 
      (HIF-1). Exposure of K562 and HeLa cells to hypoxia for 16 h resulted in a 2- to 
      3-fold increase in transferrin receptor mRNA expression. A motif with 
      multipartite organization similar to the hypoxia response element of a number of 
      hypoxia-inducible genes such as erythropoietin was identified within a 100-base 
      pair sequence upstream of the transcriptional start site. Mutation of a site 
      similar to the consensus HIF-binding site (HBS) in this motif attenuated the 
      hypoxic response by 80%. Transient co-expression of the two HIF-1 subunits 
      (HIF-1alpha and HIF-1beta) enhanced the wild type transferrin receptor promoter 
      activity, but that which contained a mutated HBS yielded no such response. 
      Electrophoretic mobility shift assays revealed that HIF-1 was stimulated and 
      bound to the transferrin receptor HBS upon hypoxic challenge. Our results 
      indicate that the transferrin receptor is a target gene for HIF-1.
FAU - Lok, C N
AU  - Lok CN
AD  - The Lady Davis Institute for Medical Research, Jewish General Hospital Department 
      of Physiology, McGill University, Montreal, Quebec, Canada H3T 1E2.
FAU - Ponka, P
AU  - Ponka P
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 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Iron-Regulatory Proteins)
RN  - 0 (Iron-Sulfur Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Receptors, Transferrin)
RN  - 0 (Transcription Factors)
RN  - E1UOL152H7 (Iron)
SB  - IM
MH  - Base Sequence
MH  - Cell Hypoxia/*genetics
MH  - DNA-Binding Proteins/physiology
MH  - Gene Expression Regulation
MH  - HeLa Cells
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Iron/metabolism
MH  - Iron-Regulatory Proteins
MH  - Iron-Sulfur Proteins/metabolism
MH  - K562 Cells
MH  - Molecular Sequence Data
MH  - Nuclear Proteins/physiology
MH  - Promoter Regions, Genetic
MH  - RNA-Binding Proteins/metabolism
MH  - Receptors, Transferrin/*genetics
MH  - *Response Elements
MH  - *Transcription Factors
EDAT- 1999/08/14 00:00
MHDA- 1999/08/14 00:01
CRDT- 1999/08/14 00:00
PHST- 1999/08/14 00:00 [pubmed]
PHST- 1999/08/14 00:01 [medline]
PHST- 1999/08/14 00:00 [entrez]
AID - S0021-9258(19)55541-7 [pii]
AID - 10.1074/jbc.274.34.24147 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Aug 20;274(34):24147-52. doi: 10.1074/jbc.274.34.24147.