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(Received for publication, March 12, 1997, and in revised form, June 24, 1997)
From the Cardeza Foundation for Hematologic Research, Department of
Medicine, Jefferson Medical College of Thomas Jefferson University,
Philadelphia, Pennsylvania 19107-5099
The hypoxia-inducible factor 1 transcriptional
activator complex (HIF-1) is involved in the activation of the
erythropoietin and several other hypoxia-responsive genes. The HIF-1
complex is composed of two protein subunits: HIF-1
Volume 272, Number 36,
Issue of September 5, 1997
pp. 22642-22647
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
(HIF-1) Protein Is Rapidly
Degraded by the Ubiquitin-Proteasome System under Normoxic
Conditions
ITS STABILIZATION BY HYPOXIA DEPENDS ON REDOX-INDUCED
CHANGES
/ARNT (aryl
hydrocarbon receptor nuclear translocator), which is constitutively
expressed, and HIF-1
, which is not present in normal cells but
induced under hypoxic conditions. The HIF-1 subunit is continuously
synthesized and degraded under normoxic conditions, while it
accumulates rapidly following exposure to low oxygen tensions. The
involvement of the ubiquitin-proteasome system in the proteolytic
destruction of HIF-1 in normoxia was studied by the use of specific
inhibitors of the proteasome system. Lactacystin and MG-132 were found
to protect the degradation of the HIF-1 complex in cells transferred from hypoxia to normoxia. The same inhibitors were able to induce HIF-1
complex formation when added to normoxic cells. Final confirmation of
the involvement of the ubiquitin-proteasome system in the regulated degradation of HIF-1 was obtained by the use of
ts20TGR cells, which contain a
temperature-sensitive mutant of E1, the ubiquitin-activating enzyme.
Exposure of ts20 cells, under normoxic conditions, to the
non-permissive temperature induced a rapid and progressive accumulation
of HIF-1. The effect of proteasome inhibitors on the normoxic induction
of HIF-1 binding activity was mimicked by the thiol reducing agent
N-(2-mercaptopropionyl)-glycine and by the oxygen radical
scavenger 2-acetamidoacrylic acid. Furthermore, N-(2-mercaptopropionyl)-glycine induced gene expression as
measured by the stimulation of a HIF-1-luciferase expression vector and by the induction of erythropoietin mRNA in normoxic Hep 3B cells. These last findings strongly suggest that the hypoxia induced changes
in HIF-1 stability and subsequent gene activation are mediated by
redox-induced changes.
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|
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|
|
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|
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|
|
|
|
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|
|
|
|
|
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|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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