ORE, a Eukaryotic Minimal Essential Osmotic Response Element

Ferraris, Joan D.; Williams, Chester K.; Jung, Kyu-Yong; Bedford, Jennifer J.; Burg, Maurice B.; García-Peréz, A.

doi:10.1074/jbc.271.31.18318

Cited by 161 publications

(112 citation statements)

References 22 publications

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“…The AKR1B1 gene is upregulated by tonicity e.g. NaCl where increased AKR1B1 activity would cause tissues to maintain osmolarity by converting glucose to sorbitol (41,42), Figure 8. The regulatory element on the gene promoter is referred to as the Osmotic Response Element (ORE) and the transcription factors that bind to the ORE are likely to be regulated by a MAP Kinase module (43).…”

Section: Figure 7 Role Of Akrs In the Metabolism Of Aflatoxinmentioning

confidence: 99%

Introduction and Overview of the Aldo-Keto Reductase Superfamily

Penning

2003

ACS Symposium Series

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Aldo-Keto Reductases (AKRs) are a rapidly growing gene superfamily involved in the formation of hyperosmotic sugars, which can contribute to diabetic complications. They also metabolize reactive aldehydes, prostaglandins, steroid hormones, chemical carcinogens and drugs. These enzymes (>115) are generally monomeric, cytosolic, NAD(P)Hdependent-oxidoreductases, that share high sequence identity -(<40%) and similar three-dimensional-structures e.g., (α/β) 8 -barrels and belong to 14 families. For a complete listing of the 14 families visit: www.med.upenn.edu/akr. AKRs detoxify endogenous toxicants, e.g., cytotoxic/mutagenic bifunctional electrophiles derived from the decomposition of lipid hydroperoxides. AKRs also metabolize exogenous toxic substances. They play a role in tobacco-carcinogenesis since they catalyze the detoxication of nicotine derived nitrosaminoketones and activate polycyclic aromatic trans-dihydrodiols to yield reactive and redox active ortho-quinones. Discrete isozymes also detoxify mycotoxin metabolites, e.g., aflatoxin dialdehyde and protect against hepatocellular carcinoma. The aflatoxin reductases are induced by cancer chemopreventive agents, e.g., ethoxyquin. Evidence is mounting that AKRs are stress regulated genes and play a central role in the cellular response to osmotic, electrophilic and oxidative stress.

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Section: Figure 7 Role Of Akrs In the Metabolism Of Aflatoxinmentioning

confidence: 99%

Introduction and Overview of the Aldo-Keto Reductase Superfamily

Penning

2003

ACS Symposium Series

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“…Response of 59-flanking region of MCP1 gene to hypertonic stress (17,18). Thus, to identify the cis-acting regulatory enhancer elements within the MCP1 gene, which is responsive to hypertonic stress, the promoter region (2939 to +59) of the MCP1 gene, which contains the putative MCP1-TonE/ORE, was isolated, and a series of deletion constructs were created for luciferase reporter assay.…”

Section: Signaling Pathways Participating In Induction Of Mcp1 Expresmentioning

confidence: 99%

“…Moreover, based on experiments with deletion mutant constructs (Fig. 8), 59-TGGA-AAAACACCAA-39 is an essential sequence for functional activity in response to hypertonicity and falls within the uniform consensus sequence of TonE/ORE, 59-(C/T)GGAANNN(C/T)N(C/T)-39 (16), or 59-NGGAAA(A/T)(T/A/G)(C/A/T)(A/C)C-39 (17,18). When compared with the transcriptional activity between MCP1-TonE/ORE 32 and 33, the activities were almost equivalent (Fig.…”

Section: Probementioning

confidence: 99%

“…Investigations further identified the TonEBP (13)/OREBP (14)-also known as NFAT5 (15)-as a transcription factor that binds to the TonE/ORE enhancer element. It has been also reported that the consensus sequence of the TonE/ORE is the 59-(C/T)GGAANNN(C/T)N(C/T)-39 and/or 59-NGGAAA (A/T)(T/A/G)(C/A/T)(A/C)C-39 in the canine BGT1 gene (16) and/ or AR gene (17,18), respectively. In addition to the BGT1 and AR genes, the TonE/ORE has been identified in the proximal region of the 59-flanking region of stress protein genes, such as Hsp70 (19) and Osp94 (20), which protect cells from the deleterious effects of hyperosmolity.…”

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confidence: 99%

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Hypertonicity-Induced Expression of Monocyte Chemoattractant Protein-1 through a Novel Cis-Acting Element and MAPK Signaling Pathways

Kojima

Taniguchi

Tsuzuki

et al. 2010

The Journal of Immunology

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MCP1 is upregulated by various stimuli, including LPS, high glucose, and hyperosmolality. However, the molecular mechanisms of transcriptional regulation of the MCP1 gene under hyperosmolar conditions are poorly understood. Treatment of NRK52E cells with NaCl or mannitol resulted in significant elevation of MCP1 mRNA and protein in a time- and dose-dependent manner. Treatment with a p38MAPK inhibitor (SB203580), an ERK inhibitor (PD98059), or an MEK inhibitor (U0126), suppressed the increase in MCP1 expression caused by hypertonic NaCl, whereas a JNK inhibitor (SP600125) and an AP1 inhibitor (curcumin) failed to attenuate MCP1 mRNA expression by NaCl. In the 5′-flanking region of the MCP1 gene, there is a sequence motif similar to the consensus TonE/ORE as well as the consensus C/E binding protein (BP), NF-κB, and AP1/Sp1 sites. Luciferase activity in cells transfected with reporter constructs containing a putative TonE/ORE element (MCP1-TonE/ORE) enhanced reporter gene expression under hypertonic stress. Results of electrophoretic gel mobility shift assay showed a slow migration of the MCP1-TonE/ORE probe, representing the binding of TonEBP/OREBP/NFAT5 to this enhancer element. These results indicate that the 5′-flanking region of MCP1 contains a hypertonicity-sensitive cis-acting element, MCP1-TonE/ORE, as a novel element in the MCP1 gene. Furthermore, p38MAPK and MEK–ERK pathways appear to be, at least in part, involved in hypertonic stress-mediated regulation of MCP1 expression through the MCP1-TonE/ORE.

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“…ALR2 was also regulated by extracellular osmolytes (24,25) and an osmotic response element has been found in the rabbit ALR2 gene (26). The different members of the aldo-keto reductase superfamily are clearly important in a number of cellular defense and developmental mechanisms.…”

Section: Table IVmentioning

confidence: 99%

Cloning, Sequencing, and Enzymatic Activity of an Inducible Aldo-Keto Reductase from Chinese Hamster Ovary Cells

Hyndman¹,

Takenoshita²,

Vera³

et al. 1997

Journal of Biological Chemistry

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Treatment of Chinese hamster ovary (CHO) cells by the aldehyde containing calpain inhibitor I resulted in the induction of a 35-kDa protein that was partially sequenced and shown to be a member of the aldo-keto reductase superfamily (Inoue, S., Sharma, R. C., Schimke, R. T., and Simoni, R. D. (1993) J. Biol. Chem. 268, 5894 -5898). Using rapid amplification of cDNA ends polymerase chain reaction, we have sequenced the cDNA for this protein (CHO reductase). This enzyme is a new member of the aldo-keto reductase superfamily and shows greatest amino acid sequence identity to mouse fibroblast growth factor-regulated protein and mouse vas deferens protein (92 and 80% sequence identity, respectively). The enzyme exhibits about 70% sequence identity with the aldose reductases (ALR2; EC 1.1.1.21) and about 47% with the aldehyde reductases (ALR1; EC 1.1.1.2). Northern analysis showed that it is induced in preference to either ALR1 or ALR2 and RNase protection assays showed gene expression in bladder, testis, jejunum, and ovary in descending order of expression. The cDNA for this inducible reductase was cloned into the pET16b vector and expressed in BL21(DE3) cells. Expressed CHO reductase showed kinetic properties distinct from either ALR1 or ALR2 including the ability to metabolize ketones. This protein joins a growing number of inducible aldo-keto reductases that may play a role in cellular regulation and protection.To characterize the calpain inhibitor I-sensitive protease(s) involved in the degradation of 3-hydroxy-3-methylglutaryl-CoA reductase, Simoni's group (1) attempted to isolate Chinese hamster ovary (CHO) 1 cells resistant to this peptide aldehyde (N-acetyl-leucyl-leucyl-norleucinal (ALLN)). Instead of inducing a protease, a 35-kDa protein was overexpressed which gave tryptic peptide fragments with a high degree of sequence identity to members of the aldo-keto reductase superfamily. 2 This superfamily is a rapidly growing group of monomeric oxidoreductases containing at least 40 members at present (2). This group includes the aldehyde and aldose reductases, a number of hydroxysteroid dehydrogenases, Shaker channels, and plant chalcone reductases. They are characterized by a TIM-barrel structure (3) and the preferential use of NADPH over NADH. Substrates include aliphatic and aromatic aldehydes, monosaccharides, steroids, prostaglandins, polycyclic aromatic hydrocarbons, and isoflavinoid phytoalexins.Several members of this family have been shown to be induced in response to hormonal or chemical factors. These include fibroblast growth factor-regulated protein (FR-1) (4), mouse vas deferens protein (MVDP) (5), aldose reductase (ALR2) (6 -8), and dihydrodiol dehydrogenase (9). To determine the relationship of this new reductase to the other members of the family we have used RACE PCR to isolate and sequence its mRNA from CHO cells. It shows highest sequence identity to FR-1 and MVDP at 92 and 80%, respectively. FR-1 and MVDP have not been extensively characterized kinetically but CHO reductase showed a greater ...

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ORE, a Eukaryotic Minimal Essential Osmotic Response Element

Cited by 161 publications

References 22 publications

Introduction and Overview of the Aldo-Keto Reductase Superfamily

Introduction and Overview of the Aldo-Keto Reductase Superfamily

Hypertonicity-Induced Expression of Monocyte Chemoattractant Protein-1 through a Novel Cis-Acting Element and MAPK Signaling Pathways

Cloning, Sequencing, and Enzymatic Activity of an Inducible Aldo-Keto Reductase from Chinese Hamster Ovary Cells

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