A nuclear factor other than Sp1 binds the GC-rich promoter of the gene encoding rat poly(ADP-ribose) polymerase in vitro

Laniel, Marc-André; Bergeron, Marie-Josée; Poirier, Guy G.; Guérin, Sylvain L.

doi:10.1139/bcb-75-4-427

Cited by 18 publications

(22 citation statements)

References 27 publications

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“…A detailed examination of the DNA sequence from the ␣ 5 FRE indeed revealed the presence of a perfect half-palindromic site for NF1 (TGGCA; see Figs. 2B and 10) that has been previously reported to bind this transcription factor (44,45).…”

Section: Methodsmentioning

confidence: 86%

Expression of the α5 Integrin Subunit Gene Promoter Is Positively Regulated by the Extracellular Matrix Component Fibronectin through the Transcription Factor Sp1 in Corneal Epithelial Cells in Vitro

Larouche

Leclerc

Salesse³

et al. 2000

Journal of Biological Chemistry

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The accumulation of fibronectin (FN) in response to corneal epithelium injury has been postulated to turn on expression of the FN-binding integrin ␣ 5 ␤ 1 . In this work, we determined whether the activity directed by the ␣ 5 gene promoter can be modulated by FN in rabbit corneal epithelial cells (RCEC). The activity driven by chloramphenicol acetyltransferase/␣ 5 promoter-bearing plasmids was drastically increased when transfected into RCEC grown on FN-coated culture dishes. The promoter sequence mediating FN responsiveness was shown to bear a perfect inverted repeat that we designated the fibronectin-responsive element (FRE). Analyses in electrophoretic mobility shift assays provided evidence that Sp1 is the predominant transcription factor binding the FRE. Its DNA binding affinity was found to be increased when RCEC are grown on FN-coated dishes. The addition of the MEK kinase inhibitor PD98059 abolished FN responsiveness suggesting that alteration in the state of phosphorylation of Sp1 likely accounts for its increased binding to the ␣ 5 FRE. The FRE also proved sufficient to confer FN responsiveness to an otherwise unresponsive heterologous promoter. However, site-directed mutagenesis indicated that only the 3 half-site of the FRE was required to direct FN responsiveness. Collectively, binding of FN to its ␣ 5 ␤ 1 integrin activates a signal transduction pathway that results in the transcriptional activation of the ␣ 5 gene likely through altering the phosphorylation state of Sp1.Corneal wounds account for a substantial proportion of all visual disabilities and medical consultations for ocular problems in North America. They can be superficial with damage limited to the epithelium or associated with a deeper involvement of the epithelial basement membrane and of the stromal lamella. Severe recurrent and persistent corneal wounds are most commonly secondary to ocular diseases and damage such as recurrent erosion, mild chemical burns, superficial herpetic infections, neuroparalytic cornea, autoimmune diseases, and stromal ulcerations due to viral or bacterial infections or to severe burns (1). Despite currently available treatments, many of these corneal wounds persist for weeks and months or else recur frequently and can progress to corneal perforation.Tissue repair requires cell migration, proliferation, and adhesion. Cell adhesion and migration in turn require extracellular matrix (ECM) 1 synthesis and assembly. ECM is a complex, cross-linked structure of proteins and polysaccharides. It organizes the geometry of normal tissues. Fibronectin (FN) is an ECM adhesion protein identified as a potential wound healing agent because of its cell attachment, migration, differentiation, and orientation properties (for a review see Refs. 2-4). In the unwounded rat eye, FN is observed by immunohistological staining at the level of the corneal epithelium basement membrane (5-7). Shortly after corneal injury, the basal cells that border the injured area and stromal keratocytes start producing massive amounts of FN (5,[8]...

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Section: Methodsmentioning

confidence: 86%

Expression of the α5 Integrin Subunit Gene Promoter Is Positively Regulated by the Extracellular Matrix Component Fibronectin through the Transcription Factor Sp1 in Corneal Epithelial Cells in Vitro

Larouche

Leclerc

Salesse³

et al. 2000

Journal of Biological Chemistry

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“…Mean AE SD of three independent experiments. transcription factors such as Sp1, Sp3 (32), and NF1 (33). However, the increase in PARP1 protein in nasopharyngeal carcinoma was unlikely to be due to an increase in transcription because no significant variation in PARP1 mRNA between nasopharyngeal carcinoma and nasopharyngeal epithelial cell lines was observed (Fig.…”

Section: Discussionmentioning

confidence: 92%

PARP1 Is Overexpressed in Nasopharyngeal Carcinoma and Its Inhibition Enhances Radiotherapy

Chow

Man

Mao

et al. 2013

Molecular Cancer Therapeutics

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Nasopharyngeal carcinoma is a rare but highly invasive cancer. As options of agents for effective combination chemoradiotherapy for advanced nasopharyngeal carcinoma are limited, novel therapeutic approaches are desperately needed. The ubiquitin ligase CHFR is known to target PARP1 for degradation and is epigenetically inactivated in nasopharyngeal carcinoma. We present evidence that PARP1 protein is indeed overexpressed in nasopharyngeal carcinoma cells in comparison with immortalized normal nasopharyngeal epithelial cells. Tissue microarray analysis also indicated that PARP1 protein is significantly elevated in primary nasopharyngeal carcinoma tissues, with strong correlation with all stages of nasopharyngeal carcinoma development. We found that the PARP inhibitor AZD2281 (olaparib) increased DNA damage, cell-cycle arrest, and apoptosis in nasopharyngeal carcinoma cells challenged with ionizing radiation or temozolomide. Isobologram analysis confirmed that the cytotoxicity triggered by AZD2281 and DNAdamaging agents was synergistic. Finally, AZD2281 also enhanced the tumor-inhibitory effects of ionizing radiation in animal xenograft models. These observations implicate that PARP1 overexpression is an early event in nasopharyngeal carcinoma development and provide a molecular basis of using PARP inhibitors to potentiate treatment of nasopharyngeal carcinoma with radio-and chemotherapy.

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“…37) or the target sequence for human HeLa CTF/NF-I (5Ј-GATCTTATTTTGGATGAAGCCAATATG-AG-3Ј; Ref. 42) were 5Ј-32 P-end-labeled as described previously (43) and used as probes.…”

Section: Methodsmentioning

confidence: 99%

“…3 The human promoter has been shown to contain binding sites for transcription factors Sp1, AP-2 (30), YY1 (32), and Ets (33), whereas the mouse promoter was recently shown to be down-regulated by a complex of adenovirus E1A protein and pRb (34). In the case of the rat PARP-1 (rPARP) proximal promoter, we have shown that it is highly but not completely dependent on five Sp1 binding sites (35,36), and that other nuclear proteins, including one likely belonging to the nuclear factor 1 (NF1) family of transcription factors (37), bind to and potentially regulate rPARP promoter transcription.…”

mentioning

confidence: 92%

Nuclear Factor 1 Interferes with Sp1 Binding through a Composite Element on the Rat Poly(ADP-ribose) Polymerase Promoter to Modulate Its Activity in Vitro

Laniel

Poirier

Guérin

2001

Journal of Biological Chemistry

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Poly(ADP-ribose) polymerase-1 (PARP-1) catalyzes the rapid and extensive poly(ADP-ribosyl)ation of nuclear proteins in response to DNA strand breaks, and its expression, although ubiquitous, is modulated from tissue to tissue and during cellular differentiation. PARP-1 gene promoters from human, rat, and mouse have been cloned, and they share a structure common to housekeeping genes, as they lack a functional TATA box and contain multiple GC boxes, which bind the transcriptional activator Sp1. We have previously shown that, although Sp1 is important for rat PARP1 (rPARP) promoter activity, its finely tuned modulation is likely dependent on other transcription factors that bind the rPARP proximal promoter in vitro. In this study, we identified one such factor as NF1-L, a rat liver isoform of the nuclear factor 1 family of transcription factors. The NF1-L site on the rPARP promoter overlaps one of the Sp1 binding sites previously identified, and we demonstrated that binding of both factors to this composite element is mutually exclusive. Furthermore, we provide evidence that NF1-L has no effect by itself on rPARP promoter activity, but rather down-regulates the Sp1 activity by interfering with its ability to bind the rPARP promoter in order to modulate transcription of the rPARP gene.Poly(ADP-ribose) polymerase-1 (PARP-1) 1 is a nuclear enzyme which catalyzes the addition of ADP-ribose units from nicotinamide adenine dinucleotide (NAD ϩ ) onto itself and other nuclear proteins such as histones and topoisomerases (reviewed in Refs. 1 and 2). It is made up of three functional domains, namely the amino-terminal DNA-binding domain, the central automodification domain, and the carboxyl-terminal catalytic domain (3). Although PARP-1 is often associated with DNA repair, because of its rapid and extensive activation following DNA damage (4, 5), it has also been implicated in other major nuclear functions such as transcription (6, 7), DNA replication (8, 9) and recombination (10). PARP-1 is also important for cell differentiation (11-13) and is involved in cell death, likely acting as a molecular switch between apoptosis and necrosis (14).PARP-1 is expressed in all organs, albeit at varying degrees, with highest mRNA expression found in brain, thymus, heart, and testis (15, 16). PARP-1 mRNA level is regulated at the cell cycle level, reaching its peak at either the G 1 (17-20) or the S phases (21, 22). It has also been shown that a decrease in PARP-1 mRNA levels is associated with cellular differentiation (23-26) and senescence (27), whereas an increase is observed upon activation of lymphocytes (17, 28) or peripheral blood mononuclear cells (18). All these studies show that, although PARP-1 is ubiquitously expressed, its modulation, likely through complex transcriptional regulation, is critical to major cellular functions.In order to better understand the transcriptional mechanisms regulating PARP-1 expression, the PARP-1 gene promoter has been identified and cloned from three mammalian species, human (29, 30), rat (31), ...

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A nuclear factor other than Sp1 binds the GC-rich promoter of the gene encoding rat poly(ADP-ribose) polymerase in vitro

Cited by 18 publications

References 27 publications

Expression of the α5 Integrin Subunit Gene Promoter Is Positively Regulated by the Extracellular Matrix Component Fibronectin through the Transcription Factor Sp1 in Corneal Epithelial Cells in Vitro

Expression of the α5 Integrin Subunit Gene Promoter Is Positively Regulated by the Extracellular Matrix Component Fibronectin through the Transcription Factor Sp1 in Corneal Epithelial Cells in Vitro

PARP1 Is Overexpressed in Nasopharyngeal Carcinoma and Its Inhibition Enhances Radiotherapy

Nuclear Factor 1 Interferes with Sp1 Binding through a Composite Element on the Rat Poly(ADP-ribose) Polymerase Promoter to Modulate Its Activity in Vitro

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