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Cellular response to cancer chemopreventive agents: Contribution of the antioxidant responsive element to the adaptive response to oxidative and chemical stress
Abstract
Cancer chemopreventive agents can act by inhibiting either the acquisition of mutations or the neoplastic processes that occur subsequent to mutagenesis. Compounds that reduce the rate at which mutations arise, referred to as blocking agents, exert their effects largely through their ability to induce the expression of antioxidant and detoxification proteins. This is achieved by the transcriptional activation of a small number of genes that are co-regulated through the presence of an antioxidant responsive element (ARE) in their promoters. Blocking agents can cause gene induction by producing oxidative and/or chemical stress within the cell and, as the inducible proteins act to ameliorate the metabolic insult, the process represents a form of adaptive response. The transcription factors which mediate this response through the ARE are members of the basic leucine zipper superfamily. The mechanism whereby cells sense and respond to the chemical signal(s) generated by chemopreventive blocking agents is discussed.
... Different MAPK can affect the activation of Nrf2 and thus affect the expression of heme oxygenase 1 (HO-1). Previous studies [15] have found, by analyzing amino acid sequences, that the interaction between MAPK and Nrf2 may be related to the presence of MAPK protein phosphorylation sites in the reverse activation domain of Nrf2. The possible mechanism by which p38 promotes Nrf2/HO-1 activation and expression is that p38 phosphorylates Nrf2 and separates it from Keap1 in the cytosol, thereby promoting the activation of Nrf2 [16,17]. ...
The purpose of this study was to establish the relationship between mitogen-activated protein kinase (MAPK) and Nrf2 signaling pathways in Echinococcus granulosus (E. granulosus). E. granulosus protoscoleces (PSCs) cultured in vitro were divided into different groups: a control group, PSCs were pretreated with various concentrations of propofol followed by exposure to hydrogen peroxide (H2O2), and PSCs were pretreated with MAPK inhibitors, then co-treated with propofol and incubated in the presence of H2O2. PSCs activity was observed under an inverted microscope and survival rate was calculated. Reactive oxygen species (ROS) was detected by fluorescence microscopy, western blotting was used to detect the expression of Nrf2, Bcl-2, and heme oxygenase 1 (HO-1) in the PSCs among different groups. Pretreatment of PSCs with 0–1 mM propofol for 8 h prevented PSCs death after exposure to 0.5 mM H2O2. PSCs were pretreated with PD98059, SB202190, or SP600125 for 2 h, co-treated with propofol for an additional 8 h, and then exposed to 0.5 mM H2O2 for 6 h. On day 6, the PSCs viability was 42% and 39% in the p38 and JNK inhibitor groups, respectively. Additionally, pretreatment with propofol significantly attenuated the generation of ROS following H2O2 treatment. Propofol increased the expression of Nrf2, HO-1, and BCL2 compared with that of the control group. Pretreatment PSCs with SP600125 or SB202190, co-incubation with propofol and H2O2, can reduce the expression of Nrf2, HO-1, and BCL2 (p < 0.05). These results suggest that propofol induces an upregulated expression of HO-1 and Nrf2 by activation of the JNK and p38 MAPK signaling pathways. This study highlights the cross role of metabolic regulation of ROS signaling and targeting signalling pathways that may provide a promising strategy for the treatment of E. granulosus disease.
... The GSTP1 gene has been demonstrated to harbor a regulatory antioxidant response element 47 that may be indirectly activated by PAH. 48 However, tissue-specific factors may be involved in the regulation of GSTP1 transcription. The fact that this enzyme shows a high level of constitutive expression may also be a reason why no changes were observed. ...
Studies suggest that resveratrol (trans‐3,4′,5‐trihydroxystilbene), which is a diphenolic antioxidant found in plants and foods, has cancer chemopreventive and chemotherapeutic potential. A lower risk of lung cancer among consumers of wine compared with consumers of other beverages has been observed, which may be partly attributed to the high content of resveratrol particularly in red wine. We have studied the effect of resveratrol on the expression of genes involved in the metabolism of polycyclic aromatic hydrocarbons in the human bronchial epithelial cell line BEP2D. Expression of the cytochrome P450 1A1 (CYP1A1) and 1B1 (CYP1B1), microsomal epoxide hydrolase (mEH), and glutathione S‐transferase P1 (GSTP1) genes was measured by quantitative reverse transcriptase‐polymerase chain reaction. The cells were treated either with benzo[a]pyrene or 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin in the presence or absence of resveratrol. Resveratrol inhibited both the constitutive and the induced expression of CYP1A1 and CYP1B1 in a dose‐dependent manner. In contrast, the expression of the mEH gene was increased in response to resveratrol and no change in the expression of GSTP1 was found. The altered gene expression in response to resveratrol was reflected in a reduced overall level of benzo[a]pyrene metabolism. These data indicate that resveratrol may exert lung cancer chemopreventive activity through altering the expression of genes involved in the metabolism of polycyclic aromatic hydrocarbons, resulting in altered formation of carcinogenic benzo[a]pyrene metabolites in human bronchial epithelial cells. © 2001 Wiley‐Liss, Inc.
... It has been shown that ZER induced phase II detoxification enzymes in cultured rat normal liver epithelial cell lines . There is a large body of evidence that phase II detoxification enzymes play a major role in the cellular detoxification of oxidative damaging, genotoxic and carcinogenic chemicals (Hayes et al., 1999) and associated with significantly reduced risk of several cancers (Zhao et al., 2001;Fowke et al., 2003). However, the aim of this study was to evaluate for the first time, the clastogenic effects of ZER on human PBL in vitro. ...
Objective: Several natural products are being increasingly used in the treatment of cancer to minimize the adverse side effects of cancer chemotherapy. Zerumbone (ZER), the sesquiterpene derived from Zingiber zerumbet Smith, has been reported to have an in vitro anticancer effects against various human tumour cells as well as in vivo against a number of induced malignancies in mice. Previously we have reported the genotoxic effects of ZER in vitro against CHO cell lines. Material and Method: The aim of this study was to investigate the genotoxic effects of the combination of ZER along with cisplatin in CHO cells. Two cytogenetic endpoints were used, namely Chromosomal Aberrations assay (CA) and Micronucleus test (MN). Both cytogenetic endpoints were performed without any metabolic activation. Result: ZER treated cultures showed the significant increase in the frequency of the chromosome aberrations and MN induction. In CA assay, marked changes have been observed after co-treatment of CHO cell lines with different concentration of ZER along with 5 µM Cisplatin when compared to ZER treatment alone, suggesting a possible synergistic genetoxic effects. Whereas, treatment of CHO cell lines with different concentrations of ZER along with 2.5 µM Cisplatin was found to reduce chromosomal aberrations, suggesting an antagonistic genotoxic effect. On the other hand, in MN induction test, co-treatment of CHO cell lines with both 2.5 µM and 5 µM Cisplatin and different concentration of ZER found to reduce the genotoxic effects compared to the 2.5 µM and 5 µM Cisplatin alone suggesting an antagonistic genotoxic effect.Conclusion: The genotoxic effects of combined low concentrations of Cisplatin with different concentrations of ZER could have an antagonist genotoxic potential in vitro in CHO cell lines.
... GSH can be reproduced from glutathione disulfide (GSSG) via the glutathione reductase (GSR) enzyme. It has been shown to be effective against ROS and to defend neuronal toxic insults [9][10][11]. A deficiency of glutathione in the brain is associated with Parkinson's disease, Alzheimer's disease, seizures, and other neurodegenerative diseases [12,13]. ...
Protocatechuic acid (PCA) is a type of phenolic acid found in green tea and has been shown to have potent antioxidant and anti-inflammatory properties. However, the effect of PCA on pilocarpine seizure-induced neuronal death in the hippocampus has not been evaluated. In the present study, we investigated the potential therapeutic effects of PCA on seizure-induced brain injury. Epileptic seizure was induced by intraperitoneal (i.p.) injection of pilocarpine (25 mg/kg) in adult male rats, and PCA (30 mg/kg) was injected into the intraperitoneal space for three consecutive days after the seizure. Neuronal injury and oxidative stress were evaluated three days after a seizure. To confirm whether PCA increases neuronal survival and reduced oxidative injury in the hippocampus, we performed Fluoro-Jade-B (FJB) staining to detect neuronal death and 4-hydroxynonenal (4HNE) staining to detect oxidative stress after the seizure. In the present study, we found that, compared to the seizure vehicle-treated group, PCA administration reduced neuronal death and oxidative stress in the hippocampus. To verify whether a decrease of neuronal death by PCA treatment was due to reduced glutathione (GSH) concentration, we measured glutathione with N-ethylmaleimide (GS-NEM) levels in hippocampal neurons. A seizure-induced reduction in the hippocampal neuronal GSH concentration was preserved by PCA treatment. We also examined whether microglia activation was affected by the PCA treatment after a seizure, using CD11b staining. Here, we found that seizure-induced microglia activation was significantly reduced by the PCA treatment. Therefore, the present study demonstrates that PCA deserves further investigation as a therapeutic agent for reducing hippocampal neuronal death after epileptic seizures.
... Treatment with ECT induced an increase in HO-1 (Fig. 4A) and GCLC (Fig. 4B) protein expressions in a dose-dependent manner. Induction of phase II and antioxidant enzymes is known to be essential for protecting cells from oxidative insults (34). Nrf2 is a transcription factor that responds to oxidative stress by activating antioxidant genes, including HO-1 and GCLC. ...
This study was conducted to investigate the anti-adipogenic activity of esculetin (ECT) which is reported to be attributable to the modulation of antioxidant enzymes during adipogenesis. After six days of ECT treatment of 3T3-L1 cells, lipid accumulation was determined by Oil red O staining. The levels of glutathione (GSH) and reactive oxygen species (ROS), and the activities of antioxidant enzymes including glutathione reductase, glutathione peroxidase (GPx), and catalase were examined. In addition, the protein expression of glutamate-cysteine ligase catalytic subunit (GCLC) and heme oxygenase-1 (HO-1) was measured by Western blot. ECT significantly inhibited lipid accumulation by approximately 80% and ROS production in a concentration-dependent manner. GSH level and GPx activity were increased by ECT by approximately 1.3-fold and 1.7-fold compared to the control group, respectively. GCLC and HO-1 expression were elevated by ECT. These results showed that ECT treatments strongly inhibit adipogenesis, increase GSH level, and upregulate the expression of GCLC and HO-1, possibly by decreasing ROS production in 3T3-L1 cells during adipogenesis.
... They are considered as an attractive target to the treatment of brain problem. The antioxidant reagents could capture the free radicals directly, and so they show a great activity as neuro-protective agents [3,4] and chemo-protective agents [5][6][7][8][9][10][11]. Moreover, the spirocyclic compounds have nonplanar chiral structure, and so they have been considered as multifunctional agents in biomolecules. ...
The regioselective spiroindoline derivatives were afforded via multi-componant reaction. Its process was one of the green chemistry (simplicity, mild conditions, and atomic economy). The electron repelling and attracting groups affected on reactivity of the azomethine ylides (increase EHOMO value). All compound structures were confirmed by spectroscopic data and elemental analysis. The antibacterial and antioxidant activities for these synthesized compounds could be investigated; the highly antioxidant activity was observed with compounds, which proved to possess high HOMO values, and the highly antibacterial activity was observed against S. aureus, B. cereus, S. marcesens, and P. mirabilis, which proved to possess low HOMO values.
... The reduced form of glutathione, GSH, is a tripeptide that exists interchangeably with the oxidized form, GSSG (Noctor and Foyer 1998). Glutathione provides the cell with multiple defenses, not only against reactive species, but also against other toxic insults, like xenobiotics (Hayes et al. 1999). Į-Tocopherol is another important molecule, which prevents lipid peroxidation (Bartoli et al. 1999). ...
Small quantities of reactive species of oxygen and nitrogen are produced in physiological processes occurring in all organisms. However, when they are formed in excess or when the antioxidant defence system is depleted, homeostasis is disrupted favouring pro-oxidants. Loss of oxidative status has been linked to several diseases. Thus, antioxidants compounds may assist the prevention and therapeutics of diseases in which oxidative phenomena are involved, e.g. cancer, chronic inflammatory disease, cardiovascular disorders and aging. There are several synthetic compounds with antioxidant properties, although their use has been restricted due to their toxicity. So, there is a growing interest on the search of natural compounds with antioxidant potential, which may exhibit improved tolerability. Natural matrices have proven antioxidant activity, which is due to their chemical composition. These matrices present a wide range of low molecular weight phytochemicals, like alkaloids, carotenoids and organic acids, which constitute the basis of their antioxidant capacity. Phenolic compounds are among those with more interest, because they are largely distributed in nature and can exert their antioxidant activity at several levels. As different natural matrices have distinct compounds contents, with several structures, they offer different protective mechanisms. In this chapter we describe different vegetable matrices, like Catharanthus roseus, Passiflora edulis, Rumex induratus and insect-plant system considerations, involving Pieris brassicae. All refered matrices display antioxidant activity, with special attention being given to their phenolic compounds. Because no single method is able to provide exact information about antioxidant potential, some methods currently used to assess this capacity will be referred.
The freshwater red-eared slider turtle, Trachemys scripta elegans, experiences weeks to months of anoxia at the bottom of ice-locked bodies of water in the winter. While this introduces anoxia-reoxygenation cycles similar to the ischemia-reperfusion events that mammals experience, T. s. elegans does not suffer any apparent tissue damage. To survive prolonged anoxia and prevent cellular damage associated with reactive oxygen species, these turtles have developed numerous adaptions, including highly effective antioxidant defenses. Herein, we examined the subcellular localization and protein expression of nuclear factor erythroid-2-related factor 2 (Nrf2), a central transcription factor responsible for modulating cellular antioxidant responses, that was found to be upregulated and localized to the nucleus in anoxic turtles. Additionally, we examined protein levels of glutathione S-transferases (GSTs) and manganese superoxide dismutase (MnSOD) antioxidant enzymes in anoxic liver, kidney, heart, and skeletal muscle tissues. MnSOD levels were significantly higher in heart and muscle during anoxia, and the four GST isozymes (GSTK1, GSTT1, GSTP1, and GSTM3) were elevated in a tissue-specific manner during anoxia and/or aerobic recovery. Together, these results indicate that Nrf2 is likely involved in activating downstream antioxidant genes in response to anoxic stress. These results provide a possible Nrf2-mediated transcriptional mechanism that supports existing findings of enhanced antioxidant defenses that allow T. s. elegans to cope with anoxia-reoxygenation cycles, and subsequent oxidative stress.
It is becoming increasingly clear that neurological disorders are multifactorial, involving disruptions in multiple cellular systems. Thus, while each disease has its own initiating mechanisms and pathologies, certain common pathways appear to be involved in most, if not all, neurological disorders described to date. These include alterations in redox homeostasis, gene transcription, protein modification and processing, neurotrophic factor signaling, mitochondrial function, and the immune response. Therefore, it is unlikely that hitting a single target will result in significant benefits to patients with a neurological disorder.1,2 However, current drug research efforts are almost exclusively focused on single protein targets and the identification of small molecules that can modulate these targets with high affinity.³ Thus, for the treatment of neurological disorders, it may be necessary to use combinations of drugs directed against different targets. However, this approach is subject to a number of potential problems, including pharmacokinetic and bioavailability challenges, which in central nervous system (CNS) disorders are exacerbated by the difficulty of getting multiple compounds across the blood-brain barrier and the potential for drug-drug interactions. An alternative approach is to identify small molecules that have multiple biological activities that are relevant to neurological disorders.
Aging comes about not as the result of any genetic program but rather as the consequence of the fact that there is no selective pressure not to age. Thus, the age of onset consequence , the rate of senescence, and the length of the life span are inherently modifiable, as it has been shown by recent basic biogerontologic research. The main, but not the exclusive, mechanism underlying the loss of function characteristic of aging is oxidative stress. When laboratory animal models are caused by selection, mutation, or transgenes to live long, they almost always do so because of changes in gene expression patterns that give them an enhanced resistance to oxidative stress. Application of the basic knowledge gained by bioerontologic research should soon lead pharmaceutical interventions into the aging process.
A number of studies have demonstrated that the proliferative capacity of cells declines with aging. In particular, epidermal growth factor (EGF)-stimulated DNA synthesis is reduced in hepatocytes from aged rats relative to young rats. Growth factor stimulation activates a genetic program in large part regulated by a family of mitogen-activated protein kinases (MAPK) that phosphorylate and thereby activate transcription factors involved in controlling the expression of proliferation-associated genes. In the present study, we compared the activation of the extracellular signal-regulated kinase 2 (ERK2) and c-Jun N-terminal kinase 1 (JNK1) MAPK in EGF-stimulated hepatocytes derived from young (6-month) and aged (24-month) rats. JNK activity was not appreciably altered by EGF treatment of cells from either age group. In contrast, ERK2 was highly activated by EGF treatment, but the magnitude of activation was significantly lower in hepatocytes of aged animals compared to those of young animals (7-fold versus 20-fold, respectively). The reduced ERK2 activity in response to EGF was associated with decreased c-fos and c-jun mRNA expression and lower levels of AP-1 transcription factor DNA binding activity in the aged hepatocytes. Finally, the basal expression of MAPK phosphatase 1, a MAPK-regulated gene involved in regulating MAPK activity, was higher in aged hepatocytes. Taken together, these findings suggest that an alteration in the balance between MAP kinase-phosphatase activities could contribute to the age-related decline in proliferative capacity.
Thioredoxin (TRX) is a pleiotropic cellular factor that has thiol-mediated redox activity and is important in regulation of
cellular processes, including proliferation, apoptosis, and gene expression. The activity of several transcription factors
is posttranslationally altered by redox modification(s) of specific cysteine residue(s). One such factor is nuclear factor
(NF)-κB, whose DNA-binding activity is markedly augmented by TRX treatment in vitro. Similarly, the DNA-binding activity of activator protein 1 (AP-1) is modified by a DNA repair enzyme, redox factor 1 (Ref-1),
which is identical to a DNA repair enzyme, AP endonuclease. Ref-1 activity is in turn modulated by various redox-active compounds,
including TRX. We here report the molecular cascade of redox regulation of AP-1 mediated by TRX and Ref-1. Phorbol 12-myristate
13 acetate efficiently translocated TRX into the HeLa cell nucleus where Ref-1 preexists. This process seems to be essential
for AP-1 activation by redox modification because co-overexpression of TRX and Ref-1 in COS-7 cells potentiated AP-1 activity
only after TRX was transported into the nucleus by phorbol 12-myristate 13 acetate treatment. To prove the direct active site-mediated
association between TRX and Ref-1, we generated a series of substitution-mutant cysteine residues of TRX. In both an in vitro diamide-induced cross-linking study and an in vivo mammalian two-hybrid assay we proved that TRX can associate directly with Ref-1 in the nucleus; also, we demonstrated the
requirement of cysteine residues in the TRX catalytic center for the potentiation of AP-1 activity. This report presents an
example of a cascade in cellular redox regulation.
Activation of the transcription factor NF-κB by tumor necrosis factor (TNF) and interleukin-1 (IL-1) requires the NF-κB-inducing kinase (NIK). In a yeast two-hybrid screen for NIK-interacting proteins, we have identified a protein kinase previously known as CHUK. Overexpression of CHUK activates a NF-κB-dependent reporter gene. A catalytically inactive mutant of CHUK is a dominant-negative inhibitor of TNF-, IL-1-, TRAF-, and NIK-induced NF-κB activation. CHUK associates with the NF-κB inhibitory protein, IκB-α, in mammalian cells. CHUK specifically phosphorylates IκB-α on both serine 32 and serine 36, modifications that are required for targeted degradation of IκB-α via the ubiquitin-proteasome pathway. This phosphorylation of IκB-α is greatly enhanced by NIK costimulation. Thus, CHUK is a NIK-activated IκB-α kinase that links TNF- and IL-1-induced kinase cascades to NF-κB activation.
The induction of phase II detoxifying enzymes is an important defense mechanism against intake of xenobiotics. While this group of enzymes is believed to be under the transcriptional control of antioxidant response elements (AREs), this contention is experimentally unconfirmed. Since the ARE resembles the binding sequence of erythroid transcription factor NF-E2, we investigated the possibility that the phase II enzyme genes might be regulated by transcription factors that also bind to the NF-E2 sequence. The expression profiles of a number of transcription factors suggest that an Nrf2/small Maf heterodimer is the most likely candidate to fulfill this rolein vivo.To directly test these questions, we disrupted the murinenrf2 genein vivo.While the expression of phase II enzymes (e.g., glutathione S-transferase and NAD(P)H: quinone oxidoreductase) was markedly induced by a phenolic antioxidantin vivoin both wild type and heterozygous mutant mice, the induction was largely eliminated in the liver and intestine of homozygousnrf2-mutant mice. Nrf2 was found to bind to the ARE with high affinity only as a heterodimer with a small Maf protein, suggesting that Nrf2/small Maf activates gene expression directly through the ARE. These results demonstrate that Nrf2 is essential for the transcriptional induction of phase II enzymes and the presence of a coordinate transcriptional regulatory mechanism for phase II enzyme genes. Thenrf2-deficient mice may prove to be a very useful model for thein vivoanalysis of chemical carcinogenesis and resistance to anti-cancer drugs.
Chemical carcinogens play a very significant role in the etiology of cancer in man. This chapter describes a number of compounds that have the capacity to inhibit the neoplastic effects of chemical carcinogens when administered either prior to exposure to the carcinogen or at the same time. The carcinogens have a common reactive form—namely, a positively charged electrophilic species that binds to macromolecules. Most of the inhibitors are synthetic compounds and exhibit great diversity of chemical structures. The chapter emphasizes on two groups of inhibitors that have relatively low toxicity. The first group includes antioxidants and some related compounds. These were initially selected for investigation because of the possibility that they can have a scavenging effect on reactive carcinogenic species. This group of inhibitors exerts an inhibitory effect when administered shortly before the carcinogen around 2-4 hours. The second group includes compounds that have as a common property the capacity to alter the activity of the microsomal mixed-function oxidase system. Most of these compounds induce an increase in mixed function oxidase activity and have a maximum effectiveness when administered 24 -48 hours prior to challenge by the carcinogen. The chapter also discusses test systems used for studying the inhibitors of chemical carcinogenesis and outlines their mechanism of action.
The human NAD(P)H:quinone oxidoreductase (NQO1) gene, 1850 base pairs (bp) of the 5' flanking region, and 67 bp of the 3' flanking region have been sequenced. The human NQO1 gene is approximately 20 kb in length and has six exons interrupted by five introns. The start site of transcription was determined by primer extension analysis. The first exon is 118 bp in length and codes for two amino acids including the initiating methionine and one G for the first codon of the second exon. The sixth exon is the largest among the exons and is 1833 bp in length. The sequence analysis of the sixth exon revealed the presence of four potential polyadenylation signal sequences (AATAAA) and a single copy of human Alu repetitive sequence. The second intron is the smallest of all the introns (116 bp). Nuclear run-on experiments performed using nuclei isolated from 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treated and untreated human hepatoblastoma (Hep-G2) cells demonstrated that TCDD treatment increases the rate of transcription of endogenous NQO1 gene by 3-fold.(ABSTRACT TRUNCATED AT 250 WORDS)
NAD(P)H:quinone oxidoreductases (NQOs) are flavoproteins that catalyze the oxidation of NADH or NADPH by various quinones and oxidation-reduction dyes. We have previously described a complementary DNA that encodes a dioxin-inducible cytosolic form of human NAD(P)H:quinone oxidoreductase (NQO1). In the present report we describe the nucleotide sequence and deduced amino acid sequence for a cDNA clone that is likely to encode a second form of NAD(P)H:quinone oxidoreductase (NQO2) which was isolated by screening a human liver cDNA library by hybridization with a NQO1 cDNA probe. The NQO2 cDNA is 976 nucleotides long and encodes a protein of 231 amino acids (Mr = 25,956). The human NQO2 cDNA and protein are 54% and 49% similar to human liver cytosolic NQO1 cDNA and protein, respectively. COS1 cells transfected with NQO2 cDNA showed a 5-7-fold increase in NAD(P)H:quinone oxidoreductase activity as compared to nontransfected cells when either 2,6-dichlorophenolindophenol or menadione was used as substrate. Western blot analysis of the expressed NQO1 and NQO2 cDNA proteins showed cross-reactivity with rat NQO1 antiserum, indicating that NQO1 and NQO2 proteins are immunologically related. Northern blot analysis shows the presence of one NQO2 mRNA of 1.2 kb in control and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treated human hepatoblastoma Hep-G2 cells and that TCDD treatment does not lead to enhanced levels of NQO2 mRNA as it does for NQO1 mRNA. Southern blot analysis of human genomic DNA suggests the presence of a single gene approximately 14-17 kb in length. The NQO2 gene locus is highly polymorphic as indicated by several restriction fragment length polymorphisms detected with five different restriction enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)
The expression pattern and DNA sequence of a newly identified gene, CNC (cap'n'collar), suggest a role for this gene in cephalic patterning during Drosophila embryogenesis. In situ hybridization reveals transcripts localized to the mandibular segment and the hypopharyngeal and labral primordia first detectable in late blastoderm stages. Sequence analysis of cDNA clones from the CNC locus shows the CNC gene product to be related to transcription factors of the leucine zipper (bZIP) class. Based on its protein sequence, we propose that CNC is a subunit of a heterodimeric regulatory protein involved in the control of head morphogenesis.