Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A prolonged effect of ACTH on the state of adenylate and guanylate cyclase systems in the adrenal glands of experimental animals was investigated. It was found that in guinea pigs injected with ACTH (4 units daily for 1-50 days) the weight of adrenal glands and the DNA content in these organs increased 2.0-2.5-fold by the end of experiment; the increase in both values was stepwise. The corticosteroid level in the blood varied throughout the experiment: the changes in the DNA content in adrenals and in the corticosteroid content in the blood were oppositely directed. This was accompanied by cyclic changes in the basal and stimulated activities of adenylate and guanylate cyclases and proteinases in the adrenal glands occurring with a periodicity of 6-15 days. The activity peaks for cyclases and protein kinases preceded the rise in the DNA content in the adrenals. A clearcut correlation between the changes in the enzyme activity and the hormone dose was observed. The changes in the basal and stimulated activities of guanylate cyclase seem to be due to the control of cAMP level in the cell (stimulation of cGMP-dependent cAMP phosphodiesterase). Apparently, the periodic changes in the activity of cAMP-dependent protein kinases in the cytoplasmic and nuclear fractions and a relatively high activation of nuclear protein kinases (by 30-60%) in comparison of cytoplasmic ones (8-10%) are related to stimulation of DNA synthesis. It is concluded that the changes in the activity of cyclases and protein kinases play a role in the mechanism of proliferative effect of ACTH.
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PMID:[The role of periodic changes in cyclase and protein kinase activity in the mechanism of the proliferative effect of ACTH]. 283 Sep 14

We have determined the complete genomic nucleotide sequence and analyzed the promoter region of murine guanylyl cyclase/natriuretic peptide receptor-A gene (Npr1,coding for NPRA). The gene spans about 17.8 kb and contains 22 exons interrupted by 21 introns. All the exon-intron boundaries possess the consensus GT/AG splice junctions. Four different types of short interspersed nuclear elements (ten mouse B1 elements, seven mouse B2-B4 elements, one ID and one MIR element) and one medium reiteration frequency repeats have been found in the non-coding regions of the gene. Eleven tandem repeats, including three in the promoter region of the gene, have been identified. The transcription start site, 362 bp upstream from the start codon, was determined by 5'- rapid amplification of cDNA ends. The 1.98 kb 5'-flanking region contains three potential SP1 binding sites and one inverted CCAAT box but lacks the TATA box. This region also contains several putative cis-acting motifs known to bind kidney specific nuclear protein HFH-3, cAMP-responsive element binding protein (CREB) and AP-4. In addition, the binding sites for a variety of transcription factors: AML-1 alpha, SRY, Nkx-2.5, LyF-1, p300, GATA-1/2, HNF-3 beta, c/EBP alpha/beta and USF have been localized in the promoter region of Npr1 gene. The analyses and characterization of the genomic structure of murine Npr1 gene should yield important insights into the species-specific regulation of this important gene family.
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PMID:Genomic structure, organization, and promoter region analysis of murine guanylyl cyclase/atrial natriuretic peptide receptor-A gene. 1209 86

We characterized the promoter activity of a medaka fish intestinal guanylyl cyclase gene, OlGC6, by assay of enzyme activity in response to various promoter-luciferase fusion gene constructs introduced into CACO-2 cells and medaka fish embryos. A transient transfection assay of the various fusion gene constructs showed that the nucleotides between -98 and -89 in the 5'-flanking region of the OlGC6 gene are essential for transcription of the OlGC6 gene in CACO-2, and that the OlGC6 gene fragment between -98 and +50 is sufficient to drive gene expression in the medaka fish intestine. An electrophoretic mobility shift assay and ultraviolet (UV) cross-linking experiments demonstrated that a nuclear protein from CACO-2 cells and the adult medaka fish intestinal cells binds specifically to the AGACCTTTGC nucleotides in the regulatory element.
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PMID:Promoter analysis of a medaka fish intestinal guanylyl cyclase gene. 1258 30

Polo-like kinase 1 (PLK1) is an evolutionarily conserved serine/threonine kinase essential for cell mitosis. As a master cell cycle regulator, p21/Waf1 plays a critical role in cell cycle progression. Nitric oxide (NO.) has been shown to down-regulate PLK1 and up-regulate p21/Waf1 independent of cGMP. Here, the respective roles of p38 MAPK and p21/Waf1 in NO.-mediated PLK1 repression were investigated using differentiated U937 cells that lack soluble guanylate cyclase. NO. was shown to down-regulate both PLK1 mRNA and protein. Nuclear run-on assays and mRNA stability studies demonstrated that the effect of NO. on PLK1 expression was associated with decreased transcription without changes in transcript stability. SB202190, a p38 MAPK inhibitor, prevented transcriptional repression of PLK1 by NO.. Transfection with dominant-negative p38 MAPK mutant eliminated the NO. effect on both p21/Waf1 and PLK1 gene expression. Knockdown of p21/Waf1 with siRNA also substantially reduced the regulatory effect of NO. on PLK1. Reporter gene experiments showed that NO. decreased activity of the PLK1 proximal promoter, an effect that was blocked by p38 MAPK inhibitor. Deletion or mutation of the CDE/CHR promoter site, an element regulated by p21/Waf1, increased base-line promoter activity and abolished NO. repression of the PLK1 promoter. Likewise, electrophoretic mobility shift assays with CDE/CHR probe revealed a NO.-mediated change in protein-probe complex formation. Competition with various unlabeled CDE/CHR mutant sequences showed that NO. increased nuclear protein binding to intact CHR. These results demonstrate that a NO.-p38 MAPK-p21/Waf1 signal transduction pathway represses PLK1 through a canonical CDE/CHR promoter element.
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PMID:Nitric oxide down-regulates polo-like kinase 1 through a proximal promoter cell cycle gene homology region. 1712 39

NPR1/GCA (natriuretic peptide receptor 1/guanylyl cyclase A) expression is controlled by several agents, including ANP (atrial natriuretic peptide). After ANP stimulation, NPR1/GCA down-regulates the transcriptional activity of its gene via a cGMP-dependent mechanism. Because we previously identified a cis-acting element responsible for this cGMP sensitivity, we proceed here to explore novel putative protein binding to cGMP-response element (cGMP-RE). Using the yeast one-hybrid technique with a human kidney cDNA library, we identified a strong positive clone able to bind cGMP-RE. The clone was derived from 1083-bp-long cDNA of a gene of yet unknown function localized on human chromosome 1 (1p33.36). We named this new protein GREBP (for cGMP-response element-binding protein). DNA binding assays showed 18-fold higher cGMP-RE binding capacity than the controls, whereas an electromobility shift assay indicated a specific binding for the cGMP-RE, and chromatin immunoprecipitation confirmed the binding of GREBP to the element under physiological conditions. By acting on cGMP-RE, GREBP inhibited the expression of a luciferase-coupled NPR1 promoter construct. In H295R cells, ANP heightened GREBP expression by 60% after just 3 h of treatment while inhibiting NPR1/GCA expression by 30%. Silencing GREBP with specific small interfering RNA increased the activity of the luciferase-coupled NPR1 promoter and GCA/NPR1 mRNA levels. GREBP is a nuclear protein mainly expressed in the heart. We report here the existence of a human-specific gene that acts as a transcriptional repressor of the NPR1/GCA gene.
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PMID:GREBP, a cGMP-response element-binding protein repressing the transcription of natriuretic peptide receptor 1 (NPR1/GCA). 2044 5