Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The insulin-like growth factor-II/cation-independent mannose 6-phosphate receptor (IGF-II/MPR) is a multifunctional protein that binds IGF-II and ligands containing a mannose 6-phosphate recognition marker. Recent studies have shown that this receptor plays a critical role in mammalian development, and that its expression is controlled by both epigenetic and tissue-specific factors. Our laboratory has cloned the 93-kilobase mouse gene and characterized its 48 exons. In this report we describe the structure and function of the IGF-II/MPR gene promoter. To study promoter function, a series of chimeric plasmids linking different segments of IGF-II/MPR 5' flanking DNA to the reporter gene, firefly luciferase, were transiently transfected into HepG2 and C3H 10T1/2 cells. Promoter activity was orientation-specific and was maximal (550- to 4250-fold above promoterless control) with a plasmid containing 266 base pairs (bp) of IGF-II/MPR DNA. The fusion gene accurately directed transcription as measured by ribonuclease protection assay using RNA extracted from transfected cells. DNA-protein binding studies by in vitro DNase I footprinting revealed an extended 54-bp footprint within the proximal promoter that contained two E-boxes and potential binding sites for transcription factors Sp1, NGF-IA, and related proteins. Gel mobility shift experiments with double-stranded oligonucleotides containing this region gave rise to several specific DNA-protein complexes, and the addition of specific antibodies indicated that proteins antigenically related to Sp1 and c-Myc were components of one or more of these bands. Deletion of this 54-bp segment led to an 8-fold decline in promoter activity, and its transfer to a heterologous promoter stimulated gene expression by nearly 7-fold. Mutational analyses indicated that each E box contributed to more than half of the enhancer's activity. These results define a strong minimal IGF-II/MPR promoter of no more than 266 bp and identify a 54-bp enhancer within this promoter fragment. Our observations thus represent a first step toward characterizing the developmental, epigenetic, and tissue-specific factors that control IGF-II/MPR gene expression.
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PMID:Control of insulin-like growth factor-II/mannose 6-phosphate receptor gene transcription by proximal promoter elements. 858 25

Proto-oncogenes are involved in the regulation of gene expression, for example after ligand binding to growth factor receptors. Expression of the proto-oncogenes c-fos, c-jun, c-ha-ras and c-myc was studied in in vivo grown and in vitro cultured bovine preimplantation blastocysts employing RT-PCR, ribonuclease protection assay and immunohistochemistry. Thirteen- and 14- day-old preimplantation blastocysts, i.e. stages before and during trophoblast elongation, were used. In in vivo-grown blastocysts c-fos, c-jun and c-ha-ras transcripts as well as c-Fos, c-Jun and c-Myc proteins were detected in all stages studied. Cultured blastocysts were treated with 10 nM epidermal growth factor and 10 nM transforming growth factor-alpha simultaneously. Epidermal growth factor and transforming growth factor-alpha treatment induced c-fos mRNA and c-Myc protein expression. The induction of downstream targets of the epidermal growth factor receptor by epidermal growth factor and transforming growth factor-alpha indicates a functional epidermal growth factor signal transduction pathway in elongating bovine blastocysts.
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PMID:Expression of proto-oncogenes in bovine preimplantation blastocysts. 1083 31

Fumonisin B(1) (FB(1)), a carcinogenic mycotoxin produced primarily by fungus Fusarium verticillioides in corn, causes several fatal animal diseases. In mice, liver is the primary site of its toxicity. Our previous study showed that maximum induction of interferon gamma (IFNgamma) and tumor necrosis factor alpha (TNFalpha) was observed at 4 and 8 h, respectively, after an acute po FB(1) treatment. To further investigate the time-related induction of other cytokines and genes involved in apoptosis signaling, male BALB/c mice were administered orally with either saline or 25 mg/kg of FB(1) and sampled 4 or 8 h after treatment. Expression of various genes was analyzed by ribonuclease protection assay. FB(1) treatment caused increased expression of TNFalpha and interleukin (IL)-1beta in both liver and kidney, whereas IL-1alpha and IL-1 receptor antagonist (IL-1Ra) expression was induced only in the liver. Expression of TNFalpha signaling molecules, TNF receptor 55 and receptor interacting protein, was increased in liver and kidney after FB(1) treatment. Caspase 8 expression was increased only in liver with no changes in kidney with FB(1). FB(1) treatment induced expression of Fas in liver and kidney with no alterations in Fas signaling molecules, Fas ligand, Fas-associated death domain and Fas-associated protein factor. Treatment of mice with FB(1) increased the expression of B-Myc, c-Myc and Max, oncogenic transcription factors in the kidney. FB(1) toxicity caused induction of cytokine network in liver with involvement of TNFalpha signaling pathway. Increased expression of caspase 8 involved in the TNFalpha signaling pathway may contribute to the apoptosis, whereas IL-1Ra induction could contribute to the proliferating effects observed in FB(1) toxicity.
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PMID:Fumonisin B(1)-induced alterations in cytokine expression and apoptosis signaling genes in mouse liver and kidney after an acute exposure. 1188 48

c-Myc regulates cellular proliferation, differentiation, and apoptosis. Temporal expression of c-Myc during all-trans-retinoic acid (RA)-mediated neural differentiation in murine embryonic stem cell (ES) was investigated. Correlation to the modulation of dimerizing partners Max and Mad that may influence c-Myc signaling and transcription regulation was elucidated for the first time in these cells. In RA-treated cells, increase in c-myc mRNA was detected by reverse transcriptase polymerase chain reaction on days 11 and 14 of differentiation compared with the vehicle-treated controls. The results were further corroborated by ribonuclease protection assay (RPA). Western blots revealed an increase in c-Myc protein only on day 14 of differentiation in RA-treated cells. Increases in max and mad gene transcription detected by RPA at times of elevated c-Myc in RA-treated ES cells suggest that a transient increase in c-Myc protein expression may influence differential dimerization of Myc partners needed for signaling in the neural differentiation of ES cells.
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PMID:Modulation of c-myc, max, and mad gene expression during neural differentiation of embryonic stem cells by all-trans-retinoic acid. 1206 75

The Myc family of genes regulates proliferation, differentiation, and apoptosis. Temporal expression of Myc family genes and several pro-apoptotic genes were investigated during Swiss Webster mice organogenesis after maternal treatment with an oral dose of 100 mg/kg trans-retinoic acid (RA) or vehicle on day 10 post-coitum. Reverse transcriptase-polymerase chain reaction and ribonuclease protection assay revealed decreased c-myc expression at 48 h followed by an increase at 72 h in fetuses from RA-treated dams. Increased c-Myc protein was detected at 72 h in the RA-treated group. In utero RA-treatment resulted in decreased expression of max, mad, caspases, bax, and bad genes at 48 h. Terminal uridinetriphosphate nick end-labeling (TUNEL) analysis revealed increased apoptosis at 24-48 h, followed by decreased apoptosis 72 h after in utero RA-exposure, which correlated with the decreased expression of pro-apoptotic genes noted at 48 h. Further investigations are needed to understand the role of Myc family genes during RA-mediated teratogenesis.
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PMID:Expression of c-Myc and other apoptosis-related genes in Swiss Webster mouse fetuses after maternal exposure to all trans-retinoic acid. 1212 97

Complete cell reprogramming can be achieved by the introduction of specific transcription factors, Oct4 [also known as POU class 5 homeobox 1 (Pou5f1)]; sex-determining region Y (SRY)-box 2 (Sox2); Kruppel-like factor 4 (Klf4); and myelocytomatosis viral oncogene homolog (c-Myc), into terminally differentiated mouse somatic fibroblasts. This reprogramming process may be accelerated or suppressed by various factors, including microRNAs (miRNAs). Introduction of these transcription factors or miRNAs considerably modifies the malignant phenotype of cancer cells. We studied the effect of introducing these transcription factors into two distinct colorectal cancer (CRC) cell lines, HCT116 and DLD-1, in the presence and absence of Dicer 1, ribonuclease type III (Dicer1), a critical miRNA processing enzyme. We assessed cell reprogramming based on the number of cells exhibiting alkaline phosphatase staining and an increase in embryonic stem cell-like gene expression, indicating the return of cells to an immature state. Dicer1-deficient CRC cells showed a reduced number of alkaline phosphatase-positive reprogrammed cells than wild-type (WT) cells. Before reprogramming, endogenous expression of an immature carbohydrate epitope, TRA-1-60, was high in Dicer1-deficient CRC cells, whereas after reprogramming, the expression of this epitope was increased in Dicer1-sufficient more than in Dicer1-deficient CRC cells. Our data demonstrate the critical role of miRNAs in the reprogramming process and determination of a differentiated phenotype of CRC cells.
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PMID:Dicer 1, ribonuclease type III modulates a reprogramming effect in colorectal cancer cells. 2244 87

Sepsis is a potentially fatal systemic inflammatory response syndrome caused by infection. In this study, we evaluated the effects of MCP-induced protein 1 (MCPIP1), a recently discovered inflammation-related ribonuclease, on sepsis-induced acute lung injury (ALI) and investigated the underlying mechanisms. Cecal ligation puncture and lipopolysaccharide induction were performed on Sprague-Dawley rats and RAW264.7 cells, respectively, to establish sepsis-induced ALI models. The proteasome inhibitor MG132 used as an activator of MCPIP1 overexpression, and we showed that MG132 can indeed increase the expression of MCPIP1. MCPIP1 overexpression induced by MG132 alleviated sepsis-induced pathologic changes, water content and protein leakage in the lungs, and induction of systemic inflammatory mediators, and improved the 7-day mortality rate in the model rats. We also showed that MCPIP1 p showed romoted macrophage polarization from the M1 to the M2 type in sepsis-induced ALI. Furthermore, MCPIP1-enhanced M2 polarization was inhibited by an MCPIP1-targeting small interfering RNA (siMCPIP1) in RAW264.7 cells. Further mechanistic studies showed that the promotive effect of MCPIP1 on M2 polarization was related to the inhibition of c-Jun N-terminal kinase (JNK) and its downstream transcription factor c-Myc in the in vitro model. Conversely, siMCPIP1 transfection resulted in the recovery of JNK and c-Myc expression in LPS-treated cells. Taken together, these findings indicate that MCPIP1 plays a protective role in sepsis-induced ALI by modulating macrophage polarization through inhibition of the JNK/c-Myc signaling pathway. Our study presents a potentially novel therapeutic strategy for the treatment of lung injury involving the inflammatory cascade.
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PMID:MCP-induced protein 1 attenuates sepsis-induced acute lung injury by modulating macrophage polarization via the JNK/c-Myc pathway. 3132 31