• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of narLink to Publisher's site
Nucleic Acids Res. 2004; 32(4): 1318–1324.
Published online Feb 24, 2004. doi:  10.1093/nar/gkh302
PMCID: PMC390290

Transcriptional regulation of the Drosophila catalase gene by the DRE/DREF system

Abstract

Reactive oxygen species (ROS) cause oxidative stress and aging. The catalase gene is a key component of the cellular antioxidant defense network. However, the molecular mechanisms that regulate catalase gene expression are poorly understood. In this study, we have identified a DNA replication-related element (DRE; 5′-TATCGATA) in the 5′-flanking region of the Drosophila catalase gene. Gel mobility shift assays revealed that a previously identified factor called DREF (DRE- binding factor) binds to the DRE sequence in the Drosophila catalase gene. We used site-directed mutagenesis and in vitro transient transfection assays to establish that expression of the catalase gene is regulated by DREF through the DRE site. To explore the role of DRE/DREF in vivo, we established transgenic flies carrying a catalase–lacZ fusion gene with or without mutation in the DRE. The β-galactosidase expression patterns of these reporter transgenic lines demonstrated that the catalase gene is upregulated by DREF through the DRE sequence. In addition, we observed suppression of the ectopic DREF-induced rough eye phenotype by a catalase amorphic Catn1 allele, indicating that DREF activity is modulated by the intracellular redox state. These results indicate that the DRE/DREF system is a key regulator of catalase gene expression and provide evidence of cross-talk between the DRE/DREF system and the antioxidant defense system.

INTRODUCTION

Reactive oxygen species (ROS) play an important role in cell growth, differentiation, progression and death (1). At low concentration, ROS are indispensable in various biological processes such as intracellular signaling and the immune response (2). However, higher concentrations of ROS are involved in the aging process as well as in human disease states, including cancer, ischemia, and immune and endocrine system deficiencies. As a safeguard against the accumulation of ROS, several non-enzymatic and enzymatic antioxidant activities exist (1,2). The physiological level of ROS is maintained by an antioxidant defense system including the superoxide dismutase (SOD) and catalase enzymes, which convert superoxide anions to H2O2 and oxygen, and H2O2 to water and oxygen, respectively (3,4). Recent studies have shown that the induced over-expression of antioxidant enzymes such as SOD and catalase can extend the lifespan (5,6).

The catalase gene has been isolated from human (7), rat (8), mouse (9), Drosophila (10,11) and yeast (12), and it is likely that regulated expression of the catalase gene is critical for ROS homeostasis in many settings. Several studies have demonstrated tissue-specific expression of the catalase gene in mammals (13,14). Moreover, catalase expression is regulated at the transcriptional level by both Sp1 and CCAAT-recognizing factors in HP100 and mouse muscle cells (15). In Drosophila, expression of the catalase gene during development is responsive to ecdysone and is regulated at both transcriptional and post-transcriptional levels (16), although the molecular mechanisms of this regulation are poorly understood.

The homodimeric transcription factor DNA replication-related element (DRE)-binding factor (DREF) is known to play an important role in regulating DNA replication- and cell proliferation-related genes by binding to the DRE site (5′-TATCGATA) of target genes (1722). The DRE–DREF interaction controls transcription of Drosophila mitochondrial transcription factor A gene (D-mtTFA) (23), and DREF associates with TRF2 to direct promoter-selective gene expression in Drosophila (24). Recently, a homolog of DREF (hDREF) has been identified in humans, where it may regulate genes related to cell proliferation (25).

In the present study, we have identified a DRE sequence located in the 5′-flanking region of the Drosophila catalase gene, and have investigated the role of DREF in transcriptional regulation of this gene. Our results indicate that the DRE/DREF system is a key regulator for Drosophila catalase gene expression.

MATERIALS AND METHODS

Oligonucleotides

All oligonucleotides were chemically synthesized. Sequences containing the DRE sequence or base substitutions in the catalase promoter region were as follows: catalase-DRE wild-type (wt), 5′-gatccGATGGAAATATCGATATCTTCGGCa-3′ and 3′-gCTACCTTTATAGCTATAGAAGCCGtctag-5′; catalase-DRE mutant (mut), 5′-gatccGATGGAAATTAGG ATATCTTCGGCa-3′ and 3′-gCTACCTTTAATCCTATAG AAGCCGtctag-5′. Double-stranded oligonucleotides for site-directed mutagenesis were catalaseDREmut 5′-CTATAA TCGAAATTAGGATATCTTCGGCCC-3′ and 3′-CCCGGC TTCTATAGGATTAAAGCTAATATC-5′. Oligonucleotide primers for RT–PCR were designed as follows: catalase, 5′-ggtaccCTTTGAGGTGACCCACGACA-3′ and 3′-ccatggTT GAAGAACCGGACGAGCAT-5′; DREF, 5′-ctcgagATGAG CGAAGGGGTACCA-3′ and 3′-gaggagAAAAGCCGGAGC AGCATC-5′; ribosomal protein 49 (rp49), 5′-GACAAC AGAGTCGGTCGC-3′ and 3′-CAACACGTGGTCCTT GAA-5′. Mutated bases are underlined, and lower case letters indicate the linker sequences.

Plasmid constructions

The promoter region of the catalase gene was cloned by PCR using Drosophila genomic DNA. The primers employed, containing linker sequences recognized by 5′-KpnI and 3′-XhoI, were as follows: 5′-ggtaccGTTGTGGAGAACT AGGTGCATGATC-3′ and 3′-gagctcACCTTTCATGT CCGAGTATC-3′. An amplified 1756 bp fragment (pGEM-T-catalase) containing an upstream region of the catalase gene (–1030 to +18 with respect to the transcription initiation site) was inserted into pGEM-T vector (Promega). A fragment containing the catalase promoter region excised from pGEM-T-catalase was subcloned into the EcoRI site of pBluescript II KS(–) (pBScat) and sequenced. Plasmid pBScatalase was digested with SacI and XhoI, the DNA fragment containing the catalase gene promoter region was inserted between SacI and XhoI sites of pGL2-Basic (Promega) and the resulting reporter construct was designated as pcatalase-luc. To construct the plasmids pcatalase-lacZ and pcatalaseDREmut-lacZ for transgenic flies, the catalase promoter regions with and without base-substituted mutation in the DRE were inserted into the EcoRI site of the plasmid pCaSpeR-AUG-βgal, respectively.

Site-directed mutagenesis

To obtain the pcatalaseDREmut-luc mutant reporter plasmid carrying base substitution mutations in the DRE in the 5′-flanking region of the Drosophila catalase gene, the mutagenesis reaction was carried out on double-stranded DNA of pcatalase-luc using the QuickChange™ Site-Directed Mutagenesis Kit (Stratagene). The reaction was set up essentially as recommended by the manufacturer. The mutation and the fidelity of the remaining DNA were confirmed by sequencing.

Cell culture and DNA transfection

Drosophila Kc cells (26) were grown at 25°C in M3 (BF) medium (Sigma) supplemented with 2% fetal bovine serum and 0.5% penicillin–streptomycin (Gibco-BRL). All plasmids for transfection were prepared by using the Qiagen Plasmid Kit (Qiagen). Dimethyldioctadecyl ammonium bromide-mediated transfection of Drosophila cultured cells was performed as described previously (27). Luciferase reporter assays were performed with a luminometer (TD-20/20, Turner Designs). Luciferase activities normalized to β-galactosidase activities were calculated by determining the luciferase/β-galactosidase activity ratios and by averaging the values from at least three experiments, from which means and standard errors were calculated.

Preparation of nuclear extracts

Preparation of nuclear extracts from cultured cells was performed as described elsewhere (28). Cultured Drosophila Kc cells were rinsed once with ice-cold phosphate-buffered saline (PBS). The cell pellet was collected by centrifugation at 4000 r.p.m. for 5 min and resuspended in buffer A (10 mM HEPES, 1.5 mM MgCl2, 10 mM NaCl, 0.25% NP-40, pH 7.5) and incubated on ice for 5 min, followed by centrifugation at 4000 r.p.m. for 5 min. The supernatant (cytosolic extract) was removed and the nuclei were extracted with buffer C (20 mM HEPES, 25% glycerol, 1.5 mM MgCl2, 420 mM NaCl, 0.2 mM EDTA, 0.25% NP-40, pH 7.5). The nuclei were vortexed vigorously several times over 20 min, followed by centrifugation at 14 000 r.p.m. for 5 min. The supernatant (nuclear extract) was transferred into fresh tubes, diluted 1:2 with buffer D (20 mM HEPES, 50 mM KCl, 0.2 mM EDTA, 20% glycerol, pH 7.5) and frozen at –80°C until usage.

Electrophoretic mobility shift assay (EMSA)

EMSA was performed as described earlier (22). Kc cell nuclear extracts were incubated for 10 min at room temperature in 20 µl of reaction mixture containing 10 mM HEPES (pH 7.6), 50 mM KCl, 1 mM EDTA, 5% glycerol, 0.5 mM dithiothreitol (DTT), 1 µg of sonicated herring sperm DNA and 500 ng of poly(dI–dC). Unlabeled competitor oligonucleotides or antibody were also added at this step. After that, the 32P-end-labeled catalase-DRE oligonucleotides (1 × 105 c.p.m.) were added and the mixture was further incubated for 20 min at room temperature. The retarded bands were electrophoretically resolved on a 6% non-denaturing Tris-borate-EDTA polyacrylamide gel. The gels were dried and autoradiographed on X-ray film or analyzed with a BAS 2000 imaging analyzer.

Fly stocks and establishment of transgenic flies

Fly stocks were maintained at 25°C on standard food. To establish transgenic flies carrying pcatalase-lacZ or pcatalaseDREmut-lacZ, P element-mediated germline transformation was carried out as described previously (29,30). Four independent lines were obtained with pcatalase-lacZ and pcatalaseDREmut-lacZ constructs, respectively. The line 67 carrying pcatalase-lacZ on the third chromosome and line 64 carrying pcatalaseDREmut-lacZ on the third chromosome were used in this study. The lines carrying the same fusion genes showed the same lacZ expression patterns. For ectopic expression of DREF using the GAL4-UAS system, Hsp70-GAL4 (hs-GAL4), GMR-GAL4 (31) lines and the transgenic flies carrying UAS-DREF on the second chromosome described previously (32) were used. The Catn1/TM3 strain was kindly supplied by the Bloomington Stock Center. Oregon-R was used as wild type. The UAS-DREF/+;hs-GAL4/+ flies were derived from a cross of the homozygous UAS-DREF male flies to the homozygous hs-GAL4 female flies, and +/+;hs-GAL4/+ flies were derived from a cross of the Oregon-R males to the homozygous hs-GAL4 female flies. The GMR-GAL4/+;UAS-DREF/+;Catn1/+ flies were obtained from a cross of the UAS-DREF/UAS-DREF;Catn1/TM6B females (derived from a cross of the +/SM1;Catn1/TM3 female flies to the UAS-DREF/UAS-DREF;Pre/TM6B male flies) to the males carrying pGMR-GAL4 on the X chromosome. The GMR-GAL4/+ flies derived from a cross of the GMR-GAL4/Y males to the Oregon-R females. GMR-GAL4/+;UAS-DREF/+ flies from a cross of the GMR-GAL4/Y males to the UAS-DREF/UAS-DREF females and GMR-GAL4/+;+/+;Catn1/+ flies from a cross of the GMR-GAL4/Y males to the Catn1/TM6B females were used.

RT–PCR

Total RNA from larvae was isolated with Trizol reagent (Molecular Research Center, Inc.) according to the protocol furnished by the manufacturer. cDNAs were synthesized with M-MLV-RT (Promega). The RT–PCR products were analyzed on 1.5% agarose gels stained with ethidium bromide.

X-Gal staining

The tissues were dissected and fixed for 15 min in PBS containing 1% glutaraldehyde, washed in PBS, and immersed in 0.2% 5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside (X-gal) in staining buffer containing 6.1 mM K4Fe(CN)6, 6.1 mM K3Fe(CN)6, 1 mM MgCl2, 150 mM NaCl, 10 mM Na2HPO4 and 10 mM NaH2PO4. Incubation was in the dark at 37°C.

Quantitative measurement of β-galactosidase activity in extracts

Quantitative measurements of β-galactosidase activity in extracts prepared from Drosophila bodies were carried out as described previously (30). The β-galactosidase activity was defined as absorbance units/mg of protein/h. To correct for endogenous β-galactosidase activity, extracts from the host strain (white) were included in each experiment, and this background reading was substrated from readings obtained with each transformant line.

Scanning electron microscopy

Adult flies were sputter-coated with platinum and observed under a Hitachi S-3500N scanning electron microscope in the low-vaccum mode.

RESULTS

DREF binds to the DRE sequence in the 5′-flanking region of the catalase gene

In the region between –85 and –78 with respect to the transcription initiation site of the Drosophila catalase gene, we identified a sequence identical to DRE (5′- TATCGATA) (Fig. (Fig.1A).1A). Because the sequence is located near the transcription initiation site, we considered that DREF may be involved in regulation of the catalase gene promoter. We termed this DRE sequence a catalase-DRE site.

Figure 1Figure 1
Complex formation between the DRE in the 5′-upstream region of the catalase gene and the Kc cell nuclear extract. (A) Structure of the 5′-upstream region of the catalase gene and base substitutions in the DRE. The transcription initiation ...

To examine whether DREF recognizes the putative DRE site located in the catalase promoter, a gel mobility shift assay was performed using Kc cell extracts and labeled catalase-DRE wt oligonucleotides as probe. Protein–DNA complexes were detected, and were efficiently competed by the inclusion of unlabeled catalase-DRE wt oligonucleotides in the binding reaction, but not by the inclusion of catalase-DREmut oligonucleotides carrying a base substitution in the DRE sequence (Fig. (Fig.1B,1B, lanes 3 and 4). Furthermore, the addition of an anti-DREF monoclonal antibody (monoclonal antibody 4) (33) to the binding reaction resulted in a supershift of the protein–DNA complex (Fig. (Fig.1B,1B, lane 5). These results indicate that DREF binds to the catalase-DRE site with sequence specificity.

Role of DRE in catalase gene expression

To examine the role of the DRE in catalase gene promoter activity, we constructed reporter plasmids containing the catalase promoter region (–1030 to +18 with respect to the transcription initiation site) with or without mutation in the DRE fused to a luciferase reporter (Fig. (Fig.1A).1A). The plasmids were then transfected into Drosophila Kc cells and luciferase expression levels were determined. As shown in Figure Figure2,2, mutation in the DRE resulted in extensive reduction (95%) of luciferase expression.

Figure 2
Effect of base substitution mutations in the DRE sequence on catalase gene promoter activity in Kc cells. Wild-type catalase-luc (300 ng) or selected point mutant catalaseDREmut-luc (300 ng) reporter plasmids were transiently transfected into Kc cells. ...

To investigate the role of the DRE in catalase expression in living flies, we established transgenic flies carrying the catalase promoter region with or without base-substituted mutation in the DRE fused to lacZ. Quantitative β-galactosidase activities of the transgenic larvae and adults bearing catalase–lacZ or catalaseDREmut–lacZ fusion genes were examined. The mutation in the DRE reduced the β-galactosidase expression to 85% in larvae and to 84–85% in adults as shown in Figure Figure3A.3A. We examined the expression of catalase–lacZ and catalaseDREmut–lacZ fusion gene in transgenic larvae and adults by X-gal staining. In larval tissues, the β-galactosidase expression was detected in the brain lobes, ganglions, guts and gonads of third instar larvae bearing catalase–lacZ. β-Galactosidase expression in the same tissues bearing catalaseDREmut–lacZ was significantly reduced (data not shown). In adult tissues, β-galactosidase expression was detected in the foregut, hindgut, muscle and reproductive system (Fig. (Fig.3B).3B). β-Galactosidase expression in the same tissues of adult flies carrying catalaseDREmut–lacZ were significantly reduced (Fig. (Fig.3B).3B). These results indicate that the DRE is required for tissue-specific expression of the catalase gene.

Figure 3Figure 3
Effect of the DRE sequence on catalase gene promoter activity in vivo. (A) Quantitative β-galactosidase activities of the transgenic flies bearing two copies of a catalase–lacZ or catalaseDREmut–lacZ fusion gene. Crude extracts ...

DREF over-expression stimulates catalase gene transcription

To investigate a role for DREF in catalase gene expression in vivo, ectopic expression of DREF in living flies was performed with the GAL4-UAS system (34,35). Transgenic flies carrying UAS-DREF (32) were crossed with transgenic flies carrying GAL4 cDNA placed under control of the hsp70 gene promoter (hs-GAL4). Quantitative analysis of β-galactosidase activity in total crude extracts of the larvae of a UAS-DREF/+;catalase-lacZ/hs-GAL4 line was carried out. The level of β-galactosidase activity in the heat-shocked larvae UAS-DREF/+;catalase-lacZ/hs-GAL4 was higher than that of the heat-shocked larvae +/+;catalase-lacZ/hs-GAL4 (Fig. (Fig.4A).4A). This result indicates that DREF can directly stimulate Drosophila catalase gene promoter activity in vivo.

Figure 4Figure 4
DREF over-expression can induce catalase gene expres sion in vivo. (A) β-Galactosidase activities of third instar larvae from +/+;catalase-lacZ/hs-GAL4 or UAS-DREF/+;catalase-lacZ/hs-GAL4 lines. Crude extracts were prepared ...

To confirm the upregulation of catalase expression by DREF, ectopic DREF expression in third instar larvae carrying single copies of both hs-GAL4 and UAS-DREF was examined by RT–PCR (Fig. (Fig.4B).4B). The level of catalase mRNA in the third instar larvae at 6 h after heat shock was higher than that in third instar larvae carrying a single copy of hs-GAL4 (Fig. (Fig.4B).4B). This result suggests that DREF can upregulate catalase gene expression, although we cannot exclude possible post-transcriptional effects on catalase mRNA.

Catalase amorphic Catn1 mutation suppresses the DREF over-expression-induced rough eye phenotype

In a recent study, we found that the DNA binding activity of DREF is directly modulated by elevated ROS through the effect of ROS on two cysteine residues located in the DNA-binding domain of DREF (36). One prediction of a functional relationship between DREF and catalase expression is that reducing catalase expression might suppress a phenotype associated with ectopic DREF over-expression. To test this hypothesis, we investigated whether a catalase amorphic allele Catn1 (11,37) could suppress the rough eye phenotype that results from ectopic expression of DREF in eye imaginal discs (32). Under scanning electron microscopy, all 13 eyes of the GMR-GAL4/+;UAS-DREF/+;+/+ flies examined exhibited a severe rough eye phenotype (Fig. (Fig.5B5B and F). This is consistent with the report that adult flies expressing DREF under a GMR-GAL4 driver exhibit a severe rough eye phenotype (32). Fifteen of 18 eyes of GMR-GAL4/+;UAS-DREF/+;Catn1/+ flies exhibited a suppression of the DREF-induced rough eye phenotype (Fig. (Fig.5C5C and G). This indicates that the rough eye phenotype caused by ectopic expression of DREF is suppressed by the Catn1 mutation.

Figure 5
The Catn1 amorphic allele suppresses the rough eye phenotype caused by ectopic DREF expression Scanning electron microscope images of female eyes: (A) and (E) GMR-GAL4/+;+/+;+/+, (B) and (F) GMR-GAL4/+; ...

DISCUSSION

The catalase gene is a key component of a cellular antioxidant defense network. Several studies have shown that catalase expression is regulated at the transcriptional level by both Sp1 and CCAAT-recognizing factors in mammals (13,15). The 5′-upstream region of the Drosophila catalase gene contains an ecdysone response element (ERE), a TATA-like sequence, as well as CCAAT-like box and GC boxes (38). However, the molecular mechanisms of Drosophila catalase gene regulation is not well defined. In the present study, we identified a DREF-binding sequence (catalase-DRE) in the 5′-flanking region of the Drosophila catalase gene (Fig. (Fig.1A)1A) and demonstrated that this element is required for in vitro and in vivo expression of the catalase gene. We have also shown that DREF binding to the catalase-DRE site positively regulates the catalase gene at the transcriptional level. These findings indicate that the DRE/DREF system is a key regulator of catalase gene expression in Drosophila.

In mammals, it has been reported that the expression of the catalase gene is regulated in a tissue-specific manner (13,14). The catalase mRNAs are found in liver, kidney, heart, brain, spleen, lung and muscle in mice (39). In Drosophila, it has been known that the expression of the catalase gene during development is responsive to ecdysone (16,38). In this study, the expression of catalase–lacZ containing a 1.03 kb 5′-flanking region of the catalase gene (–1030 to +18 with respect to the transcription initiation site) fused to the lacZ reporter showed the highest lacZ signal at the adult stage among various developmental stages (data not shown). This is inconsistent with major peaks of the endogenous catalase mRNA level in late third larvae and pupal stages during development (38), suggesting the existence of a regulatory element(s) in the upper region than 1.03 kb of the 5′-flanking region. Although it is the tissue-specific patterns of catalase expression that need to be confirmed by in situ hybridization, the expression of the catalase–lacZ fusion in transgenic adults was detected in the foregut, hindgut, muscle and reproductive system (Fig. (Fig.3B).3B). In addition, the expression of catalaseDREmut–lacZ in the same tissues indicated that DRE is required for the expression of the catalase gene in the foregut, hindgut, muscle and reproductive system (Fig. (Fig.3B),3B), suggesting a novel function for DREF in ROS homeostasis of these tissues.

It has been well documented that the proliferative potential decreases as the tissues age (40,41). However, the molecular mechanism for the age-related decrease in proliferation remains unknown. Several studies reported that the intracellular ROS level increased with age (42,43). We found that the catalase allele Catn1 mutation suppressed the characteristic rough eye phenotype induced by DREF (Fig. (Fig.5).5). This indicates that DREF function was altered by the Catn1 mutation and that the expression of catalase is required for DREF function. Since DREF is known to play an important role in regulating cell proliferation-related genes (1722), this suggests that expression of catalase enzymes may convey an advantage for cell proliferation. A recent study has reported a significant correlation between expression of an antioxidant enzyme and cell proliferation (44). In addition, it has been reported that the extended longevity phenotypes of Drosophila are correlated with upregulation of the antioxidant defense system genes and enzymes including SOD and catalase (45). The upregulation of catalase expression by DREF and the alteration of DREF function by redox—indicating a cross-talk between the DRE/DREF system and the antioxidant defense system—may contribute to the underlying molecular mechanism for the age-related decrease in proliferation.

ACKNOWLEDGEMENTS

We are grateful to Drs Akio Matsukage and Masamitsu Yamaguchi for DREF antibody, UAS-DREF, pGMR-GAL4 strains and valuable information, and thank the Bloomington Stock Center for hs-GAL4 and Catn1/TM3 strains. We thank Dr Peter Sherwood for valuable comments on the manuscript. This work was supported by the Korea Research Foundation Grant (KRF-2002-015-CP0332). S.Y.P. and D.J.Y. were supported by the Brain Korea 21 Project in 2003.

REFERENCES

1. Mates J.M., Perez-Gomez,C. and Nunez de Castro,I. (1999) Antioxidant enzymes and human diseases. Clin. Biochem., 32, 595–603. [PubMed]
2. Monnier V., Girardot,F., Audin,W. and Tricoire,H. (2002) Control of oxidative stress resistance by IP3 kinase in Drosophila melanogaster. Free Radic. Biol. Med., 33, 1250–1259. [PubMed]
3. Michiels C., Raes,M., Toussaint,O. and Remacle,J. (1994) Importance of Se-glutathione peroxidase, catalase and Cu/Zn-SOD for cell survival against oxidative stress. Free Radic. Biol. Med., 17, 235–248. [PubMed]
4. Aebi H. (1984) Catalase in vitro. Methods Enzymol., 105, 121–126. [PubMed]
5. Orr W.C. and Sohal,R.S. (1994) Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science, 263, 1128–1130. [PubMed]
6. Parkes T.L., Elia,A.J., Dickinson,D., Hilliker,A.J., Phillips,J.P. and Boulianne,G.L. (1998) Extension of Drosophila lifespan by overexpression of human SOD1 in moterneurons. Nature Genet., 19, 171–174. [PubMed]
7. Quan F., Korneluk,R.G., Tropak,M.B. and Gravel,R.A. (1986) Isolation and characterization of the human catalase gene. Nucleic Acids Res., 14, 5321–5335. [PMC free article] [PubMed]
8. Furuta S., Hayashi,H., Hijikata,M., Miyazawa,S., Osumi,T. and Hashimoto,T. (1986) Complete nucleotide sequence of cDNA and deduced amino acid sequence of rat liver catalase. Proc. Natl Acad. Sci. USA, 83, 313–317. [PMC free article] [PubMed]
9. Reimer D.L., Bailley,J. and Singh,S.M. (1994) Complete cDNA and 5′ genomic sequences and multilevel regulation of the mouse catalase gene. Genomics, 21, 325–336. [PubMed]
10. Orr E.C., Bewley,G.C. and Orr,W.C. (1990) cDNA and deduced amino acid sequence of Drosophila catalase. Nucleic Acids Res., 18, 3663. [PMC free article] [PubMed]
11. Griswold C.M., Matthews,A.L., Bewley,K.E. and Mahaffey,J.W. (1993) Molecular characterization and rescue of acatalasemic mutants of Drosophila melanogaster. Genetics, 134, 781–788. [PMC free article] [PubMed]
12. Murray W.W. and Rachubinski,R.A. (1987) The nucleotide sequence of complementary DNA and the deduced amino acid sequence of peroxisomal catalase of the yeast Candida tropicalis pK233. Gene, 61, 401–413. [PubMed]
13. Luo D. and Rando,T.A. (2003) The regulation of catalase gene expression in mouse muscle cells is dependent on the CCAAT-binding factor NF-Y. Biochem. Biophys. Res. Commun., 303, 609–618. [PubMed]
14. Van Remmen H., Williams,M.D., Yang,H., Walter,C.A. and Richardson,A. (1998) Analysis of the transcriptional activity of the 5′-flanking region of the rat catalase gene in transiently transfected cells and in transgenic mice. J. Cell. Physiol., 174, 18–26. [PubMed]
15. Nenoi M., Ichimura,S., Mita,K., Yukawa,O. and Cartwright,I.L. (2001) Regulation of the catalase gene promoter by Sp1, CCAAT-recognizing factors and a WT1/Egr-related factor in hydrogen peroxide-resistant HP100 cells. Cancer Res., 61, 5885–5894. [PubMed]
16. Radyuk S.N., Klichko,V.I. and Orr,W.C. (2000) Catalase expression in Drosophila melanogaster is responsive to ecdysone and exhibits both transcriptional and post-transcriptional regulation. Arch. Insect Biochem. Physiol., 45, 79–93. [PubMed]
17. Hirose F., Yamaguchi,M., Handa,H., Inomata,Y. and Matsukage,A. (1993) Novel 8-base pair sequence (Drosophila DNA replication-related element) and specific binding factor involved in the expression of Drosophila genes for DNA polymerase α and proliferating cell nuclear antigen. J. Biol. Chem., 268, 2092–2099. [PubMed]
18. Takahashi Y., Yamaguchi,M., Hirose,F., Cotterill,S., Kobayashi,J., Miyajima,S. and Matsukage,A. (1996) DNA replication-related elements cooperate to enhance promoter activity of the Drosophila DNA polymerase α 73-kDa subunit gene. J. Biol. Chem., 271, 14541–14547. [PubMed]
19. Ohno K., Hirose,F., Sakaguchi,K., Nishida,Y. and Matsukage,A. (1996) Transcriptional regulation of the Drosophila CycA gene by the DNA replication-related element (DRE) and DRE binding factor (DREF). Nucleic Acids Res., 24, 3942–3946. [PMC free article] [PubMed]
20. Ryu J.R., Choi,T.Y., Kwon,E.J., Lee,W.H., Nishida,Y., Hayashi,Y., Matsukage,A., Yamaguchi,M. and Yoo,M.A. (1997) Transcriptional regulation of the Drosophila-raf proto-oncogene by the DNA replication-related element (DRE)/DRE-binding factor (DREF) system. Nucleic Acids Res., 25, 794–799. [PMC free article] [PubMed]
21. Sawado T., Hirose,F., Takahashi,Y., Sasaki,T., Shinomiya,T., Sakaguchi,K., Matsukage,A. and Yamaguchi,M. (1998) The DNA replication-related element (DRE)/DRE-binding factor system is a transcriptional regulator of the Drosophila E2F gene. J. Biol. Chem., 273, 26042–26051. [PubMed]
22. Choi T., Cho,N., Oh,Y., Yoo,M., Matsukage,A., Ryu,Y., Han,K., Yoon,J. and Baek,K. (2000) The DNA replication-related element (DRE)–DRE-binding factor (DREF) system may be involved in the expression of the Drosophila melanogaster TBP gene. FEBS Lett., 483, 71–77. [PubMed]
23. Takata K., Yoshida,H., Hirose,F., Yamaguchi,M., Kai,M., Oshige,M., Sakimoto,I., Koiwai,O. and Sakaguchi,K. (2001) Drosophila mitochondrial transcription factor A: characterization of its cDNA and expression pattern during development. Biochem. Biophys. Res. Commun., 287, 474–483. [PubMed]
24. Hochheimer A., Zhou,S., Zheng,S., Holmes,M.C. and Tjian,R. (2002) TRF2 associates with DREF and directs promoter-selective gene expression in Drosophila. Nature, 420, 439–445. [PubMed]
25. Ohshima N., Takahashi,M. and Hirose,F. (2003) Identification of a human homologue of the DREF transcription factor with a potential role in regulation of the histone H1 gene. J. Biol. Chem., 278, 22928–22938. [PubMed]
26. Echalier G. and Ohanessian,A. (1970) In vitro culture of Drosophila melanogaster embryonic cells. In Vitro, 6, 162–172. [PubMed]
27. Han K. (1996) An efficient DDAB-mediated transfection of Drosophila S2 cells. Nucleic Acids Res., 24, 4362–4363. [PMC free article] [PubMed]
28. Krejsa C.M., Nadler,S.G., Esselstyn,J.M., Kavanagh,T.J., Ledbetter,J.A. and Schieven,G.L. (1997) Role of oxidative stress in the action of vanadium phosphotyrosine phosphatase inhibitors. Redox independent activation of NF-κB. J. Biol. Chem., 272, 11541–11549. [PubMed]
29. Spradling A.C. (1986) Drosophila: A Practical Approach. IRL Press, Oxford.
30. Ha H.-Y. and Yoo,M.-A. (1997) Transcriptional activation of Drosophila raf proto-oncogene in immune response. Korean J. Genet., 19, 267–276.
31. Takahashi Y., Hirose,F., Matsukage,A. and Yamaguchi,M. (1999) Identification of three conserved regions in the DREF transcription factors from Drosophila melanogaster and Drosophila virilis. Nucleic Acids Res., 27, 510–516. [PMC free article] [PubMed]
32. Hirose F., Ohshima,N., Shiraki,M., Inoue,Y.H., Taguchi,O., Nishi,Y., Matsukage,A. and Yamaguchi,M. (2001) Ectopic expression of DREF induces DNA synthesis, apoptosis and unusual morphogenesis in the Drosophila eye imaginal disc: possible interaction with Polycomb and trithorax group proteins. Mol. Cell. Biol., 21, 7231–7242. [PMC free article] [PubMed]
33. Hirose F., Yamaguchi,M., Kuroda,K., Omori,A., Hachiya,T., Ikeda,M., Nishimoto,Y. and Matsukage,A. (1996) Isolation and characterization of cDNA for DREF, a promoter-activating factor for Drosophila DNA replication-related genes. J. Biol. Chem., 271, 3930–3937. [PubMed]
34. Brand A.H. and Perrimon,N. (1993) Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development, 118, 401–415. [PubMed]
35. Fischer J.A., Giniger,E., Maniatis,T. and Ptashne,M. (1988) GAL4 activates transcription in Drosophila. Nature, 332, 853–856. [PubMed]
36. Choi T.Y., Park,S.Y., Kang,H.S., Cheong,J.H., Kim,H.D., Lee,B.L., Hirose,F., Yamaguchi,M. and Yoo,M.A. (2003) Redox regulation of DNA binding activity of DREF in Drosophila. Biochem. J., in press. [PMC free article] [PubMed]
37. Mackay W.J. and Bewley,G.C. (1989) The genetics of catalase in Drosophila melanogaster: isolation and characterization of acatalasemic mutants. Genetics, 122, 643–652. [PMC free article] [PubMed]
38. Orr W.C., Orr,E.C., Legan,S.K. and Sohal,R.S. (1996) Molecular analysis of the Drosophila catalase gene. Arch. Biochem. Biophys., 330, 251–258. [PubMed]
39. Chen X., Mele,J., Giese,H., Van Remmen,H., Dolle,M.E., Steinhelper,M., Richardson,A. and Vijg,J. (2003) A strategy for the ubiquitous overexpression of human catalase and CuZn superoxide dismutase genes in transgenic mice. Mech. Ageing Dev., 124, 219–227. [PubMed]
40. Iakova P., Awad,S.S. and Timchenko,N.A. (2003) Aging reduces proliferative capacities of liver by switching pathways of C/EBPα growth arrest. Cell, 113, 495–506. [PubMed]
41. Lorenzini A., Tresini,M., Mawal-Dewan,M., Frisoni,L., Zhang,H., Allen,R.G., Sell,C. and Cristofalo,V.J. (2002) Role of the Raf/MEK/ERK and the PI3K/Akt(PKB) pathways in fibroblast senescence. Exp. Gerontol., 37, 1149–1156. [PubMed]
42. Yen T.C., Chen,Y.S., King,K.L., Yeh,S.H. and Wei,Y.H. (1989) Liver mitochondrial respiratory functions decline with age. Biochem. Biophys. Res. Commun., 165, 944–1003. [PubMed]
43. Stadtman E.R. (1992) Protein oxidation and aging. Science, 257, 1220–1224. [PubMed]
44. Soini Y., Kaarteenaho-Wiik,R., Paakko,P. and Kinnula,V. (2003) Expression of antioxidant enzymes in bronchial metaplastic and dysplastic epithelium. Lung Cancer, 39, 15–22. [PubMed]
45. Arking R. (2001) Gene expression and regulation in the extended longevity phenotypes of Drosophila. Ann. N. Y. Acad. Sci., 928, 157–167. [PubMed]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press
PubReader format: click here to try

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links