Dual Functions of Transcription Factors, Transforming Growth Factor-β-inducible Early Gene (TIEG)2 and Sp3, Are Mediated by CACCC Element and Sp1 Sites of Human Monoamine Oxidase (MAO) B Gene

Ou, Xiao-Ming; Chen, Kevin; Shih, Jean C.

doi:10.1074/jbc.m312638200

Cited by 64 publications

(93 citation statements)

References 32 publications

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“…Inhibition of insulin gene expression by KLF11 overexpression, glucose-induced insulin secretion and regulation of endogenous KLF11 mRNA expression by glucose Although a dosedependent KLF11 overexpression-induced increase in MAOB mRNA levels was described in both SH-SY5Y and HepG2 cells [12], we did not observe significant regulation of MAOB gene expression in INS-1E beta cells (not shown). However, qPCR analysis revealed that hKLF11 overexpression significantly reduced Ins2 gene expression while Ins1 mRNA levels remained unaffected (Fig.…”

Section: Resultscontrasting

confidence: 56%

“…However, KLF11 seems to be expendable for globin gene expression since KLF11 −/− mice display normal haematopoiesis at all stages of development [18]. Interestingly, Ou et al [12] confirmed binding of KLF11 to both Sp1/GC and CACCC sites, thereby influencing the human MAOB promoter as an activator via its Sp1/ GC site or as a repressor via its CACCC site. In contrast, we could not detect binding of in vitro translated hKLF11 to the CACCC box sequence within hInsP.…”

Section: Discussionmentioning

confidence: 99%

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Human Krüppel-like factor 11 inhibits human proinsulin promoter activity in pancreatic beta cells

et al. 2007

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Aims/hypothesis The Krüppel-like factor 11 (KLF11; TIEG2), a pancreas-enriched Sp1-like transcription factor, is a known negative regulator of pancreatic exocrine cell growth. A recent study indicated KLF11-induced activation of the human proinsulin promoter (hInsP). Materials and methods We investigated the functional role of KLF11 in pancreatic beta cells. Results Endogenous KLF11 mRNA expression was found in whole rat pancreas, human pancreatic islets and INS-1E beta cells and was profoundly reduced by high glucose in INS-1E. Cotransfections of INS-1E and beta-TC3 beta cells with a human (h)KLF11 expression plasmid and an hInsP-driven reporter plasmid resulted in a substantial dose-dependent and glucose-independent inhibition of proinsulin promoter activity. 5′-deletion of hInsP demonstrated that hKLF11 acts via DNA sequences upstream of −173 and requires the beta cellspecific transcription machinery, since hKLF11-mediated inhibition of promoter activity was abolished in HEK293

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Section: Resultscontrasting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Human Krüppel-like factor 11 inhibits human proinsulin promoter activity in pancreatic beta cells

et al. 2007

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“…In generating the R1-stable cell line, SK-N-BE(2)-C cells were plated at a density of 5 ϫ 10 6 cells in a 10-cm dish. The next day the R1 expression vector or pcDNA3.1 was transfected into cells with a superfect transfection reagent (25). After 24 h, cells were replated onto 5-cm dishes, and Geneticin (G418; 600 g͞ml) was added.…”

Section: Withdrawal Of Growth Factors (Serum Starvation) and Treatmentsmentioning

confidence: 99%

“…The real-time PCR was performed with a SYBR supermix kit (Bio-Rad), and the GAPDH mRNA primer was included in every plate to avoid sample variations. A ⌬C T value was then calculated as described (25).…”

Section: Withdrawal Of Growth Factors (Serum Starvation) and Treatmentsmentioning

confidence: 99%

Monoamine oxidase A and repressor R1 are involved in apoptotic signaling pathway

Ou¹,

Chen²,

Shih

2006

Proc. Natl. Acad. Sci. U.S.A.

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147

145

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Monoamine oxidase A (MAO A) degrades serotonin, norepinephrine, and dopamine and produces reactive oxygen that may cause neuronal cell death. We have previously reported that a novel transcription factor R1 (RAM2͞CDCA7L͞JPO2) inhibits the MAO A promoter and enzymatic activities. This study reports the roles of MAO A and R1 in apoptosis and proliferation. We have found that in serum starvation-induced apoptosis, p38 kinase, MAO A, and caspase-3 were increased, whereas Bcl-2 and R1 were reduced. Using a p38 kinase inhibitor, R1 overexpression, and MAO A inhibitor, we have shown that MAO A and R1 are downstream of p38 kinase and Bcl-2, but upstream of caspase-3. Inhibition of MAO A prevents cell apoptosis. This notion was further supported by the finding that serum starvation-induced apoptosis is reduced in cortical brain cells from MAO A-deficient mice compared with WT. In addition, we found that MAO A and R1 are involved in the c-Myc-induced proliferative signaling pathway in the presence of serum. Immunoprecipitation and immunohistochemistry experiments indicate that the oncogene c-Myc colocalizes with R1 and induces R1 gene expression. Using R1 overexpression, R1 small interfering RNA, and a MAO A inhibitor, we found that R1 and MAO A act upstream of cyclin D1 and E2F1. In summary, this study demonstrates the functions of MAO A and its repressor R1 in apoptotic signaling pathways.c-Myc ͉ caspase-3 ͉ p38 kinase ͉ proliferation ͉ transcription factor M onoamine oxidases (MAOs) A and B, located on the outer mitochondria membrane with a 70% amino acid sequence identity (1, 2), catalyze the oxidative deamination of biogenic and dietary amines including monoamine neurotransmitters serotonin, norepinephrine, dopamine, and phenylethylamine. MAO plays important roles in several psychiatric and neurological disorders (3). MAO exists in two forms, MAO A and MAO B. Their catalytic activity generates H 2 O 2 and nitrogen species, which are toxic products and may cause oxidative damage to mtDNA and have potential implications for apoptosis, aging, and neurodegenerative processes (4).The in vivo function of MAO A and MAO B has been studied extensively in MAO A and MAO B knockout (KO) mice (5-7). The regulation of MAO A and MAO B gene expression by extracellular stimulation, phorbol 12-myristate 13-acetate (PMA), has also been examined. PMA selectively increases MAO B but not MAO A gene expression by activation of protein kinase C and mitogen-activated protein kinase (MAPK) signaling pathways (8).Ample evidence has indicated an important role for MAO A in apoptosis. MAO A expression has been shown to increase after the depletion of neurotrophic factor mediated by p38 kinase in PC12 cells (9). A MAO A inhibitor, clorgyline, was able to protect cells from apoptosis induced by serum starvation in human melanoma m14 cells (10). More recently, MAO A has been found to be a target of a dopaminergic neurotoxin, N-methyl-(R)-salsolinol, which leads to apoptosis in a human neuroblastoma SH-SY5Y cell line (11). This apoptotic activity co...

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“…The substrate and inhibitor specificities are influenced by a single amino acid (10). The regulations of these two genes are different (11)(12)(13). MAO inhibitors have long been used as antidepressant drugs (14), and MAO B inhibitors are used to treat Parkinson's disease (15).…”

mentioning

confidence: 99%

A Spontaneous Point Mutation Produces Monoamine Oxidase A/B Knock-out Mice with Greatly Elevated Monoamines and Anxiety-like Behavior

Chen

Holschneider

et al. 2004

Journal of Biological Chemistry

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133

126

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A spontaneous monoamine oxidase A (MAO A) mutation (A863T) in exon 8 introduced a premature stop codon, which produced MAO A/B double knock-out (KO) mice in a MAO B KO mouse colony. This mutation caused a nonsense-mediated mRNA decay and resulted in the absence of MAO A transcript, protein, and catalytic activity and abrogates a DraI restriction site. The MAO A/B KO mice showed reduced body weight compared with wild type mice. Brain levels of serotonin, norepinephrine, dopamine, and phenylethylamine increased, and serotonin metabolite 5-hydroxyindoleacetic acid levels decreased, to a much greater degree than in either MAO A or B single KO mice. Observed chase/ escape and anxiety-like behavior in the MAO A/B KO mice, different from MAO A or B single KO mice, suggest that varying monoamine levels result in both a unique biochemical and behavioral phenotype. These mice will be useful models for studying the molecular basis of disorders associated with abnormal monoamine neurotransmitters. (21), indicating that the increase in 5-HT, a preferred substrate for MAO A, and concomitant decrease in 5-HIAA may form the basis for increased aggression, consistent with the association of low 5-HIAA levels in the cerebrospinal fluid of men who exhibit aggressive behavior (22,23). Although increased aggressive behavior has not been observed in MAO B KO mice (21), low platelet MAO B activity in humans is associated with, and considered a marker for, criminal or impulsive behavior (24), although whether this is accompanied in human subjects by a concomitant decrease in MAO A activity or other related genetic or biochemical aberration is not known.MAO A/B KO mice cannot be generated through the breeding of MAO A KO and MAO B KO mice, due to the close proximity of the isoenzyme genes on the X chromosomes, where the two genes are next to each other at their 3Ј tails, organized in opposite orientations with their last exons being less than 24 kb apart (determined by blat analysis of human and mouse MAO A and B

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Dual Functions of Transcription Factors, Transforming Growth Factor-β-inducible Early Gene (TIEG)2 and Sp3, Are Mediated by CACCC Element and Sp1 Sites of Human Monoamine Oxidase (MAO) B Gene

Cited by 64 publications

References 32 publications

Human Krüppel-like factor 11 inhibits human proinsulin promoter activity in pancreatic beta cells

Human Krüppel-like factor 11 inhibits human proinsulin promoter activity in pancreatic beta cells

Monoamine oxidase A and repressor R1 are involved in apoptotic signaling pathway

A Spontaneous Point Mutation Produces Monoamine Oxidase A/B Knock-out Mice with Greatly Elevated Monoamines and Anxiety-like Behavior

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