Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies indicate that a purified protein, activin A, belongs to the transforming growth factor beta (TGF-beta) superfamily. Similar to TGF-beta, activin A can have different biologic activities, depending on the target tissues. We used recombinant activin A to demonstrate a possible regulatory role of this protein in modulating human erythroid differentiation in the human erythroid cell line, K562. Using genomic probes containing the second exon of alpha, beta, gamma, and epsilon globins, relative abundance of various types of globin transcripts in untreated and activin-treated K562 cells was examined with S1 nuclease analysis. Despite considerable homology amongst various globin sequences, these globin probes were highly specific for their unique mRNA species in the analyses. It was shown that the abundance of specific globin probe fragments for gamma and epsilon globins (209 nucleotides) as well as alpha (180 nucleotides), which were protected from S1 digestion, increased many fold in K562 cells treated with activin A. In contrast, there were no specific transcripts of beta globin detected in either the control or activin-treated cells. The increases in the level of fetal and embryonic beta-like and alpha globin transcripts also confirmed earlier studies of Northern and slot-blot analyses using globin cDNA as probes. In addition, nuclear run-off transcription assay using isolated nuclei indicated that most of the increase in the globin transcripts after activin treatment could be attributed to the stimulation of transcription rate for globin genes. Transient transfection assays also provide evidence that activin A significantly stimulated transcriptional activity of an epsilon globin promoter in K562, but not in the nonerythroid Chinese hamster ovary cells. Therefore, it was concluded that activin A exerts its effects on globin gene expression at the level of transcription in erythroid cells.
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PMID:Regulation of globin gene expression in human K562 cells by recombinant activin A. 173 15

Inhibin and activin gene expression in the ovary and in cultured granulosa cells is modulated by the pituitary gonadotropins FSH and LH. In granulosa cells, two messenger RNAs (mRNAs) of 4.3 and 3.3 kilobases (kb) encoding the common beta B-chain of inhibin and activin are observed. We demonstrate here that FSH or pharmacological agents that elevate intracellular levels of cAMP induce expression of the 4.3-kb mRNA to a greater extent than that of the 3.3-kb mRNA. To elucidate the mechanism(s) by which the two beta B transcripts are generated, we characterized the rat beta B gene and used probes from various regions of the gene to examine the structures of the beta B mRNAs. RNA blot analysis using probes from the 5'-nontranslated and flanking regions of the beta B gene revealed that the 4.3- and 3.3-kb transcripts differ in the length of their 5'-nontranslated regions. S1 nuclease protection and primer extension assays were used to map two adjacent transcriptional start sites 1051 and 1052 basepairs (bp) up-stream of the most 3'-start site previously reported for the beta B gene. These novel start sites are used to generate the 4.3-kb mRNA, whereas transcription of the 3.3-kb mRNA initiates at down-stream start sites. DNA sequence analysis did not reveal any consensus CCAAT or TATA box elements up-stream of the novel start sites. Multiple potential binding sites for the transcription factors SP1 and activator protein-2 are present throughout a region of the beta B gene from -1461 to 82 bp. Fusion genes were constructed that contain beta B sequences from -1460 to 14 bp, -1460 to -914 bp, and -913 to 14 bp controlling luciferase reporter gene expression. Analysis of beta B promoter activity in transiently transfected primary granulosa cells demonstrated that sequences flanking both the up- and down-stream transcriptional start sites have substantial basal promoter activity; however, forskolin did not affect expression of the beta B/luciferase fusion genes.
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PMID:Two messenger ribonucleic acids encoding the common beta B-chain of inhibin and activin have distinct 5'-initiation sites and are differentially regulated in rat granulosa cells. 803 18

Inhibin and activin are best known as gonadal glycoprotein hormones but have a broad anatomical distribution. We previously described the central distribution ofinhibin/activin beta A- and beta B-subunit proteins in some neuronal cell bodies, fibers, and nuclei of the rat brain and reported a possible role for central activin in suckling-induced oxytocin secretion and corticotropin releasing factor release. In the present report, we mapped the detailed immunohistochemical localization of inhibin/activin alpha-, beta A-, and beta B-subunits throughout the rat brain to further clarify their central distribution. In addition, the localization and distribution of their corresponding mRNAs was assessed. The results are summarized as follows: 1) Both beta A- and beta B-subunit immunoreactivity are found in neuronal cell bodies in the nucleus of the solitary tract and the dorsal and ventral medullary reticular nuclei, and in fibers and terminals of known projection sites for these nuclei. 2) beta B-subunit immunoreactivity is localized in a group of perifornical neurons in the hypothalamus. 3) beta A-subunit immunoreactivity is present in discrete populations of neuronal cell nuclei scattered throughout the CNS. 4) mRNAs encoding each of the inhibin/activin subunits are expressed in all major brain regions as determined by S1 nuclease assay and in a variety of specific neuroanatomical sites as shown by in situ hybridization. The results suggest that central inhibin and activin proteins are produced in the brain where they may potentially serve inter- and intracellular functions in multiple systems.
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PMID:Hybridization histochemical and immunohistochemical localization of inhibin/activin subunits and messenger ribonucleic acids in the rat brain. 882 Aug 78