Hypertension. 2001;37:419-424
(Hypertension. 2001;37:419.)
© 2001 American Heart Association, Inc.
Nuclear Factor 1 Is a Negative Regulator of gadd153 Gene Expression in Vascular Smooth Muscle Cells
Michitsugu Nakamura;
Takafumi Okura;
Yutaka Kitami;
Kunio Hiwada
From The Second Department of Internal Medicine, Ehime University School
of Medicine, Ehime, Japan.
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Abstract
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Growth
arrest and DNA damage inducible gene 153 (
gadd153) is
expressed at very low levels in growing cells but is markedly
induced
in response to cellular stresses, including glucose
deprivation, exposure to genotoxic agents, and other
growth-arresting
situations. Forced expression of GADD153 can
induce cell cycle
arrest and/or apoptosis in many types of
cells. Recently, we
reported that GADD153 was induced in vascular
smooth muscle
cells (VSMCs) in neointimal lesions of
balloon-injured carotid
arteries. To investigate the underlying
molecular mechanisms
of
gadd153 gene expression in
VSMCs, we isolated and characterized
a promoter region of the rat
gadd153 gene. Sequence alignments
of this region
revealed 1 TATA-like sequence and several well-known
cis elements. The 5'-deletion
analysis for this region showed
that a domain spanning -447
through -368 drastically reduced
the promoter activity to almost
equal levels of promoterless
control. Because this domain contained a
consensus sequence
for the nuclear factor 1 family of proteins (NF1),
DNA-binding
studies were performed by use of 2 types of NF1 consensus
probes.
Both probes were specifically shifted by nuclear extracts from
proliferating VSMCs and were supershifted by antiserum against
CCAAT
transcription factor/NF1. In addition, promoter activity
of a mutant
luciferase vector, which was generated by a point
mutation at the NF1
binding motif of the gadd153 gene, was
14-fold higher than that of a
wild-type one. These results
suggest that
gadd153 gene
expression in VSMCs is negatively
regulated by an NF1-binding motif,
and NF1 may act as an antiapoptotic
factor by continuously
suppressing
gadd153 gene expression
in growing
VSMCs.
Key Words: gadd153 gene expression apoptosis carotid arteries nuclear factor 1
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Introduction
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Growth arrest and
DNA damage inducible gene 153 (
gadd153) protein
(GADD153) is a member of the CCAAT/enhancer-binding protein
(C/EBP)
family of transcriptional
factors.
1 The expression
levels of GADD153 are very low in normal growing cells but
are highly
induced in response to a variety of cellular stresses,
including
glucose deprivation, exposure to alkylating agents,
and
other growth-arresting
situations.
2 3 4
Microinjection
of GADD153 into NIH-3T3 fibroblasts induces
G
1
arrest,
5 and
the transient
expression of GADD153 into different tumor cell
lines also leads to
growth arrest.
6 Genes
involved in cell
differentiation and growth arrest are also potential
candidates
for apoptosis
regulation.
7
In atherosclerotic and restenotic lesions, the major
cause of disease progression is believed to be excessive accumulation
of cells.8 9 This
accumulation is attributed to increased migration and/or proliferation
of cells, including vascular smooth muscle cells (VSMCs),
monocytes/macrophages, and T
lymphocytes.10 11
Recent studies have demonstrated that dysregulated apoptosis
plays an important role in the pathogenesis and progression of
cardiovascular
diseases.12 These
observations indicate that cell growth and apoptosis are 2
tightly linked processes in cardiovascular diseases,
including atherosclerosis and restenosis.
Recently, we have demonstrated that GADD153 plays an important role in
VSMC apoptosis. In a balloon-injured carotid artery, GADD153
expression was highly induced in the apoptotic VSMCs that are
often observed in neointimal
lesions.13
In the present study, to investigate underlying
molecular mechanisms of gadd153 gene expression in
VSMCs, we isolated and characterized its 5'-flanking region, which
contained a putative promoter of the gene, and showed that nuclear
factor 1 (NF1) family proteins mainly repress a basal transcriptional
activity of the gadd153 gene through binding to a
negative regulatory element (NRE) seen in its promoter
region.
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Methods
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Cloning of the Rat gadd153
Gene
A lambda DASH II rat genomic library originating from
the testes
of male Sprague-Dawley rats (Stratagene) was screened by a
rat
gadd153 cDNA as a
probe.
13 One genomic clone
containing a
12-kbp sequence of the rat
gadd153 gene
was obtained, and a
1574-bp fragment that contained the
nucleotide sequences spanning
-1480 through +94 was
excised by restriction enzyme digestion.
This fragment was subcloned
into the
SacI/
KpnI
sites of the
Bluescript II KS (+) vector (Stratagene). The resultant
plasmid
was designated as pKS-1,480, and an entire sequence of the
inserted
DNA fragment was determined on both
strands.
Cell Culture
All surgical treatments conformed to the Guide for
the Care and Use of Laboratory Animals published by the US National
Institutes of Health (NIH Publication No. 85-23, revised 1985). VSMCs
were isolated from 2 thoracic aortas of 10-week-old male Sprague-Dawley
rats (Charles River Japan Inc, Kanagawa, Japan) as described
previously.14 Cells
(passages 3 to 10) were cultured in DMEM supplemented with 10%
heat-inactivated FCS and were maintained at 37°C in a
humidified atmosphere of 95% air/5%
CO2.
Plasmid Construction Used for Promoter
Assay
Serial 5' deletions of the gadd153
gene promoter were prepared by standard methods by using a
Kilo-Sequence Deletion Kit (Takara). Seven 5' deletions, which had the
nucleotide sequences starting at the positions -1000,
-447, -367, -273, -191, -100, and -50, were selected.
Inserted DNA fragments were excised from pKS-1,480 and these 5'
deletions, and they were ligated back into the promoterless firefly
luciferase vector, pGL3-Basic (pGLB, Promega). Resultant plasmids were
designated as Luc-1,480, Luc-1,000, Luc-447, Luc-367, Luc-273, Luc-191,
Luc-100, and Luc-50. In addition, site-directed mutagenesis for an NF1
binding motif, which was located at the nucleotide
positions between -438 and -427, was performed by a recombinant
polymerase chain reaction (PCR) technique with use of Luc-447 as a
template. The mutated NF1 primer used for PCR was generated by the
sequential 3-oligonucleotide mutation at -429 to
-427 as shown in
Figure 5A, and the PCR product was sequenced and ligated
into pGLB (designated Luc-447 MT).

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Figure 5. Effect of a site-directed mutation disrupting a consensus sequence for NF1 on gadd153 gene transcription. A, Wild-type nucleotide sequence for NF1 binding motif and its point-mutated sequence (underlining). B, Relative luciferase activity of a wild-type (Luc-447) or point-mutated (Luc-447 MT) plasmid in VSMCs. Luciferase assay was performed as shown in Figure 2. Promoter activity was expressed as a relative activity to the value of Luc-447 that was set to unity. All data are expressed as mean±SE from 4 separated assays.
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Transient DNA Transfection and Luciferase
Assay
VSMCs were seeded in 60-mm dishes at a density of
5x105 cells per dish 24 hours before
transfection. Transient transfection was performed by Lipofectamine
Plus (GIBCO-BRL) as described
previously.15 Each
gadd153 promoter/firefly luciferase fusion vector (2
µg per dish) was cotransfected into VSMCs together with 0.5 µg of
pRL-CMV vector (Promega), which had a cytomegalovirus promoter in front
of a renilla luciferase cDNA. After transfection, cells were incubated
for an additional 48 hours. Luciferase assay was carried out according
to the manufacturers specifications for the Dual-Luciferase Reporter
Assay System (Promega), and the activity of renilla luciferase was used
to correct for the variation of transfection efficiency. After
sequential quantification of firefly and renilla luciferase activities
in cell lysates, the promoter activity of each plasmid was calculated
as a firefly/renilla luciferase activity ratio to obtain a relative
activity.
EMSA and Supershift Assays
Nuclear protein extraction from proliferating VSMCs,
electrophoretic mobility shift assay (EMSA), and supershift assay were
carried out as described
previously.16 The sequence
spanning -447 through -358 was divided into five 30-bp segments,
and double-stranded oligonucleotide probes (P1 to P5)
were synthesized for these segments, as shown in
Figure 3A. Two types of consensus sequences for NF1 were
prepared as probes. One is a P1 probe containing an NF1 consensus
sequence of the gadd153 gene. The other is a 25-bp double-stranded
oligonucleotide probe containing an NF1 consensus
sequence of the adenovirus 2 gene (aNF1,
5'-TTTTGGATTGAAGCCAATATGATAA-3'). Antiserum raised against recombinant
CAAT-binding transcription factor (CTF)-2, which was readily interacted
with CTF/NF1 proteins, was used for a supershift
assay.

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Figure 3. Sequences of oligonucleotide probes used for EMSA and results of EMSA with use of nuclear extracts from VSMCs. A, Sequence spanning -447 through -358 of the gadd153 gene was divided into five 30-bp segments, and double-stranded oligonucleotide probes (P1 to P5) were synthesized for these segments. B, End-labeled probes (P1 to P5) were incubated with nuclear extracts (2 µg) prepared from proliferating VSMCs, and each reaction mixture was analyzed on a 6% polyacrylamide gel (lanes 1 to 5). Lane 6 indicated only a 32P-labeled P1 probe. B1 indicates positions of specifically retarded bands; free, those of free probe.
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Results
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Isolation of the 5'-Flanking Region of the Rat
gadd153 Gene
One 12-kbp rat
gadd153 genomic clone
isolated from

1
x10
7 clones
of the rat
genomic library is shown in
Figure 1
. (The nucleotide
sequence of the rat
gadd153 gene reported in this study has
been submitted to GenBank with
accession No.
AF314033.) A 1574-bp
segment of the genomic sequence
contained a 1480-bp 5'-flanking
region and a 94-bp coding region of the
gadd153 gene. Two transcription
start sites were
identified by the primer extension method
from
poly(A)
+ RNAs (data not shown). The major
start site
with an adenine residue (A) and minor one with a thymidine
residue
(T) are indicated by asterisks. These data were completely
identical
to previous data of the hamster and human
gadd153
genes.
17 18
Hence, residue A was numbered as the nucleotide position
+1
as shown in
Figure 1
.

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Figure 1. Sequence alignments for a promoter region and its upstream cis-acting elements of the rat gadd153 gene (the nucleotide sequence of the rat gadd153 gene reported in this study has been submitted to GenBank with accession No. AF314033). Transcriptional start sites determined by primer extension analysis are indicated by asterisks, and major start site A is represented as the nucleotide position +1. A part of exon 1 is represented in boldfaced letters, and underlined sequences show notable cis-acting elements found in the 5'-flanking region. SP-1 indicates SP-1 element; AP-1, AP-1 element; ATF, activating transcription factor; GC, GC box; NF1, NF1 element; and TATA-like, variant of the TATA box.
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Putative
cis-Acting Elements Seen in
5'-Flanking Region of the Rat gadd153 Gene
A computer-assisted search for an exact match with
well-defined transcriptional
cis-acting elements revealed
the presence of a TATA-like box at -32 bp, a GC box at -153 bp, an
activator protein (AP)-1 element at -245 bp, 2
stimulatory protein (SP)-1 elements at -299 and -1480, a binding
site for the nuclear factor for interleukin (IL)-6 (NF-IL6), which
overlapped the activating transcription factor at -323 bp, 1 binding
site for NF1 at -438 bp, 2 additional sites for NF-IL6 at -478 and
-670 bp, and 1 enhancer core sequence for C/EBP, which overlapped
with another NF-IL6 at -1113 bp.
Promoter Activity of the Rat
gadd153 Gene in VSMCs
To assess a basal promoter activity of the rat
gadd153 gene in VSMCs, luciferase assay was performed
for the 8 plasmids, Luc-1,480 through Luc-50
(Figure 2). The deletion mutant Luc-367 showed the highest
promoter activity, whereas the presence of the sequence spanning -447
and -368 drastically reduced the promoter activity to the level of
promoterless plasmid, pGLB. In addition, promoter activity was markedly
reduced between Luc-273 and Luc-191.

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Figure 2. Plasmids used for luciferase assay and their relative promoter activity in VSMCs. Progressive 5' deletions, Luc-1,480 through Luc-50, had the nucleotide sequence starting at positions -1480, -1000, -447, -367, -273, -191, -100, and -50, respectively. Each plasmid (2 µg per dish) was cotransfected into VSMCs together with pRL-CMV vector (0.5 µg per dish) with use of Lipofectamine Plus. After 48 hours, luciferase assay was carried out by using the Dual-Luciferase Reporter Assay System, and the activity of renilla luciferase was used to correct for the variation of transfection efficiency. After sequential quantification of firefly and renilla luciferase activities in cell lysates, promoter activity of each plasmid was determined by the firefly/renilla luciferase ratio and was expressed as a relative activity to the value of Luc-1,480, which was set to 100%. All data are expressed as mean±SE from 4 separated assays.
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Nuclear Factors That Bind to NRE of the
gadd153 Promoter Region
A luciferase assay using 5' deletions indicated that an
80-bp segment between -447 and -368 negatively regulated a basal
promoter activity of the gadd153 gene as an NRE. To
identify the nuclear factors that actually bind to the NRE, EMSA was
performed with the use of P1 to P5 probes
(Figure 3B). Only P1 was shifted by nuclear extracts,
generating a single band (lane 1). Because P1 contained a consensus
sequence for NF1, an NF1-binding consensus probe, aNF1, was used for
EMSA as a control probe
(Figure 4). The aNF1 was also shifted by nuclear extracts,
generating a single band (lane 5) to a position almost identical with
that of P1 (lane 1). Competition experiments demonstrated that a
100-molar excess of either unlabeled P1 (lane 2) or aNF1 (lane 6)
completely competed out each shifted band. To further determine the
nature of DNA-binding proteins for P1 or aNF1, a supershift assay was
performed by using antiserum against a recombinant CTF/NF1. The P1 and
nuclear factor complex was markedly supershifted (lane 3) and the aNF1
complex was partially supershifted (lane 7) by antiserum, whereas both
bands were not supershifted by preimmune rabbit serum (lanes 4 and
8).

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Figure 4. Supershift assay using 2 types of consensus probe for NF1. Two types of NF1 consensus probe were used for the EMSA. These are P1 and aNF1 probes containing NF1 consensus sequence of the gadd153 and the adenovirus 2 gene, respectively. End-labeled P1 (lanes 1 to 4 and 9) or aNF1 (lanes 5 to 8) probe was incubated with nuclear extracts (2 µg) prepared from proliferating VSMCs. For competition experiments, a 100-molar excess of unlabeled P1 (lane 2) or aNF1 (lane 6) was incubated with nuclear extracts for 15 minutes before adding the corresponding labeled probe. Lanes 1 and 5 included no competitor, and lane 9 included no nuclear extracts. For supershift assay, 1 µL of specific antiserum against CTF/NF1 (lanes 3 and 7) or preimmune serum (lanes 4 and 8) was added to nuclear extracts before adding the labeled probe. Asterisk indicates supershifted bands; free, free probe. These data are representative of 3 separate experiments.
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Effect of Site-Directed Mutagenesis for NF1
Binding Motif on Promoter Activity
To further clarify that gadd153 gene
transcription was suppressed by an NRE, promoter activities were
compared between a wild-type (Luc-447) and a point-mutated (Luc-447 MT)
luciferase vector in VSMCs
(Figure 5). Promoter activity of Luc-447 MT was markedly
higher (14-fold) than that of Luc-447.
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Discussion
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In the present study, we isolated a 5'-flanking
region of the
rat
gadd153 gene to investigate the
transcription regulatory
mechanisms of the
gadd153
gene in growing VSMCs and identified
a specific transcriptional
repressor, NF1, which mainly regulated
a basal promoter activity of the
gene via an NRE.
Comparison of promoter activity between Luc-273 and Luc-191
indicated that the region spanning -273 and -192 acted as a basal
promoter or transcriptional activator of the
gadd153 gene
(Figure 2). Because this region has an AP-1 binding motif,
AP-1 could drive a basal promoter activity of gadd153
gene expression in growing VSMCs. Indeed, Guyton et
al19 have already
demonstrated that oxidative stresses, including
H2O2 and UV irradiation,
rapidly induce gadd153 gene expression, which is mainly mediated by an
AP-1 site in the hamster gadd153 gene. On the other
hand, promoter activity was drastically decreased by the presence of an
NRE spanning -447 and -368, which contained an NF1-binding motif.
NF1 is a family of transcription factors encoded by at least 4
different genes: NF1-A, NF1-B, NF1-C (or CTF/NF1), and NF1-X. All
isoforms share a highly conserved DNA-binding domain that recognizes a
TTGGCN5GCCAA sequence or single half sites
(TTGGC or GCCAA).20 NF1 can
either activate or repress the initiation of various gene
transcriptions. Whereas NF1 acts as a transcriptional silencer for the
genes including GLUT4,21
growth hormone,22 and
peripherin,23 it acts as a
transcriptional activator for the genes including
elastin24 and collagen
1
(I).25 In the present
study, we have reported that NF1 acted as a negative regulator for
gadd153 gene transcription via binding to an NRE seen in its promoter
region. GADD153 proteins were originally isolated on the basis of its
rapid induction by UV radiation in Chinese hamster ovary
cells,26 27 and
this expression was subsequently found to be inducible by a wide
variety of DNA damaging agents and growth arrest
treatments.6 7 8
GADD153, also known as C/EBP homologous protein-10 (CHOP-10), belongs
to the family of basic regionleucine zipper class transcriptional
factors, the C/EBP family.1
The C/EBP family participates in the process of terminal
differentiation and growth arrest in adipose
tissue.1 Recently, we
reported that the C/EBP family is also involved in cell proliferation
and apoptosis of
VSMCs.13 15
Several studies have indicated that GADD153 is directly associated with
the apoptosis induced by anticancer agents in many types of
tumor cell lines, including ovarian
cancer,28
leukemia,29 and prostatic
cancer.30 A direct
relationship between GADD153 expression and apoptosis has been
proven by the study of mice carrying null mutations in the
gadd153/CHOP-10 gene. Mouse embryonic fibroblasts
derived from CHOP-10-/- animals exhibited significantly less
apoptosis on exposure to agents that perturb cellular functions
of endoplasmic reticulum, such as tunicamycin and calcium ionophore
A23187, compared with that of wild-type
animals.31 The critical
importance of GADD153 function is observed in the signaling cascade of
apoptotic cells exposed to endoplasmic reticular stress. In
response to endoplasmic reticular stress, GADD153 is induced and
phosphorylated via a pathway involving p38
mitogen-activated protein kinase, and the
phosphorylated protein can enhance the function or gene
transcription of gadd153
itself.32 Furthermore,
Brenner et al33 have
reported that Fas-induced apoptosis in human leukemic Jurkat
cells is directly mediated by phosphorylation of
GADD153 via p38 mitogen-activated protein kinase. Very
recently, we determined that GADD153 expression was highly induced in
the apoptotic VSMCs that were frequently observed in
neointimal lesions of the balloon-injured carotid
artery.13 All these
observations indicate that the NF1 family acts as a transcriptional
repressor of the gadd153 gene in VSMCs and probably
acts as an antiapoptotic factor by continuing suppression of
gadd153 gene expression in growing
VSMCs.
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Acknowledgments
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This work was supported in part by
Grant-in-Aid for Scientific
Research from the Ministry of Education,
Science, Sports, and
Culture of Japan (Nos. 11838012 and 12470155),
from a Japanese
Heart Foundation Grant for Research on Hypertension and
Vascular
Metabolism, and from the Takeda Medical
Foundation. Antiserum
raised against recombinant CTF-2 was generously
provided by
Dr Naoko Tanese, Department of Microbiology, New York
University,
NY.
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Footnotes
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Reprint requests to Takafumi Okura, MD, The Second Department
of Internal Medicine, Ehime University School of Medicine, Onsen-gun,
Ehime 791-0295, Japan.
Received October 24, 2000;
first decision November 30, 2000;
accepted December 14, 2000.
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References
|
|---|
-
Cao Z,
Umek RM, McKnight SL. Regulated expression of three C/EBP isoforms
during adipose conversion of 3T3-L1 cells.
Genes Dev. 1991;5:15381552.[Abstract/Free Full Text]
-
Carlson SG, Fawcett
TW, Bartlett JD, Bernier M, Holbrook NJ. Regulation of the
C/EBP-related gene gadd153 by glucose deprivation.
Mol Cell Biol. 1993;13:47364744.[Abstract/Free Full Text]
-
Eizirik DL,
Bjàrklund A, Cagliero E. Genotoxic agents increase expression of
growth arrest and DNA damage-inducible genes gadd 153 and gadd 45 in
rat pancreatic islets.
Diabetes. 1993;42:738745.[Abstract]
-
Price BD,
Calderwood SK. Gadd45 and gadd153 messenger RNA levels are increased
during hypoxia and after exposure of cells to agents which
elevate the levels of the glucose-regulated proteins.
Cancer Res. 1992;52:38143817.[Abstract/Free Full Text]
-
Barone MV, Crozat
A, Tabaee A, Philipson L, Ron D. CHOP (GADD153) and its oncogenic
variant, TLS-CHOP, have opposing effects on the induction of G1/S
arrest. Genes Dev. 1994;8:453464.[Abstract/Free Full Text]
-
Zhan Q, Lord K A,
Alamo I Jr, Hollander MC, Carrier F, Ron D, Kohn KW, Hoffman B,
Liebermann DA, Fornace AJ Jr. The gadd and MyD genes define a novel set
of mammalian genes encoding acidic proteins that synergistically
suppress cell growth. Mol Cell
Biol. 1994;14:23612371.[Abstract/Free Full Text]
-
Selvakumaran M, Lin
H-K, Sjin R-T, Reed JC, Liebermann DA, Hoffman B. The novel primary
response gene MyD118 and the proto-oncogenes myb, myc, and bcl-2
modulate transforming growth factor ß1-induced apoptosis of
myeloid leukemia cells. Mol Cell
Biol. 1994;14:23522360.[Abstract/Free Full Text]
-
Barrett TB, Benditt
EP. Platelet-derived growth factor gene expression in human
atherosclerotic plaques and normal artery wall.
Proc Natl Acad Sci
U S A. 1988;85:28102814.[Abstract/Free Full Text]
-
Wilcox JN, Smith
KM, Williams LT, Schwartz SM Gordon D. Platelet-derived growth
factor mRNA detection in human atherosclerotic plaques by in situ
hybridization. J Clin
Invest. 1988;82:11341143.
-
Ross R. The
pathogenesis of atherosclerosis: a perspective for the
1990s. Nature. 1993;362:801809.[Medline]
[Order article via Infotrieve]
-
Fuster V, Badimon
L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery
disease and the acute coronary syndromes.
N Engl J Med. 1992;326:242250.[Medline]
[Order article via Infotrieve]
-
deBlois D, Tea
B-S, Dam T-V, Tremblay J, Hamet P. Smooth muscle apoptosis
during vascular regression in spontaneously hypertensive rats.
Hypertension. 1997;29:340349.[Abstract/Free Full Text]
-
Igase M, Okura T,
Nakamura M, Takata Y, Kitami Y, Hiwada K. The role of GADD153 in
vascular smooth muscle cell apoptosis.
Clin Sci. In
press.
-
Okura T, Kitami
Y, Iwata T, Hiwada K. Quantitative measurement of extra-renal renin
mRNA by polymerase chain reaction. Biochem
Biophys Res Commun. 1991;179:2531.[Medline]
[Order article via Infotrieve]
-
Fukuoka T, Kitami
Y, Okura T, Hiwada K. Transcriptional regulation of the
platelet-derived growth factor a receptor gene via
CCAAT/enhance-binding protein-
in vascular smooth muscle cells.
J Biol Chem. 1999;274:2557625582.[Abstract/Free Full Text]
-
Takata Y, Kitami
Y, Fukuoka T, Okura T, Hiwada K. Novel
cis element for tissue-specific
transcription of rat platelet-derived growth factor ß-receptor
gene. Hypertension. 1999;33:298302.[Abstract/Free Full Text]
-
Luethy JD,
Fargnoli J, Park JS, Fornace AJ Jr, Holbrook NJ. Isolation and
characterization of the hamster gadd153 gene: activation of promoter
activity by agents that damage DNA. J
Biol Chem. 1990;265:1652116526.[Abstract/Free Full Text]
-
Park JS, Luethy
JD, Wang MG, Fargnoli J, Fornace AJ Jr, McBride OW, Holbrook NJ.
Isolation, characterization and chromosomal localization of human
GADD153 gene. Gene. 1992;116:259267.[Medline]
[Order article via Infotrieve]
-
Guyton KZ, Xu Q,
Holbrook HJ. Induction of the mammalian stress response gene
GADD153 by oxidative stress: role of AP-1 element.
Biochem J. 1996;314:547554.
-
Gronostajski RM.
Roles of the NF1/CTF gene family in transcription and development.
Gene. 2000;249:3145.[Medline]
[Order article via Infotrieve]
-
Cooke DW, Lane
MD. The transcription factor nuclear factor I mediates repression of
the GLUT4 promoter by insulin. J Biol
Chem. 1999;274:1291712924.[Abstract/Free Full Text]
-
Roy RL, Guérin
SL. The 30-kDa rat liver transcription factor nuclear factor 1 binds
the rat growth-hormone proximal silencer.
Eur J Biochem. 1994;219:799806.[Medline]
[Order article via Infotrieve]
-
Adams AD, Choate
DM, Thompson MA. NF1-L is the DNA-binding component of the protein
complex at the peripherin negative regulatory element.
J Biol Chem. 1995;270:69756983.[Abstract/Free Full Text]
-
Degterev A,
Foster JA. The role of NF-1 factors in regulation of elastin gene
transcription. Matrix Biol. 1999;18:295307.[Medline]
[Order article via Infotrieve]
-
Nehls MC, Rippe
RA, Veloz L, Brenner DA. Transcription factors nuclear factor I and Sp1
interact with the murine collagen
1 (I) promoter.
Mol Cell Biol. 1991;11:40654073.[Abstract/Free Full Text]
-
Fornace AJ Jr,
Alamo I Jr, Hollander MC. DNA damage-inducible transcripts in mammalian
cells. Proc Natl Acad Sci
U S A. 1988;85:88008804.[Abstract/Free Full Text]
-
Fornace AJ Jr,
Nebert DW, Hollander MC, Luethy JD, Papathanasiou M, Fargnoli J,
Holbrook NJ. Mammalian genes coordinately regulated by growth arrest
signals and DNA-damaging agents. Mol Cell
Biol. 1989;9:41964203.[Abstract/Free Full Text]
-
Delmastro DA, Li
J, Vaisman A, Solle M, Chaney SG. DNA damage inducible-gene expression
following platinum treatment in human ovarian carcinoma cell
lines. Cancer Chemother
Pharmacol. 1997;39:245253.[Medline]
[Order article via Infotrieve]
-
Eymin B, Dubrez
L, Allouche M, Solary E. Increased gadd153 messenger RNA level is
associated with apoptosis in human leukemic cells treated with
etoposide. Cancer Res. 1997;57:686695.[Abstract/Free Full Text]
-
Lin XS, Denmeade
SR, Cisek L, Issacs JT. Mechanism and role of growth arrest in
programmed (apoptotic) death of prostatic cancer cells induced
by thapsigargin. Prostate. 1997;33:201207.[Medline]
[Order article via Infotrieve]
-
Zinszner H,
Kuroda M, Wang X, Batchvarova N, Lightfoot RT, Remotti H, Atevens JL,
Ron D. CHOP is implicated in programmed cell death in response to
impaired function of the endoplasmic reticulum.
Genes Dev. 1998;12:982995.[Abstract/Free Full Text]
-
Wang X, Ron D.
Stress-induced phosphorylation and activation of the
transcription factor CHOP (GADD153) by p38 MAP kinase.
Science. 1996;272:13471349.[Abstract]
-
Brenner B,
Koppenhoefer U, Weinstock C, Linderkamp O, Lang F, Gulbins E. Fas- or
ceramide-induced apoptosis is mediated by a Rac1-regulated
activation of Jun N-terminal kinase/p38 kinases and GADD153.
J Biol Chem. 1997;272:2217322181.[Abstract/Free Full Text]
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