Control of expression of an integrated Rous sarcoma provirus in rat cells: role of 5' genomic duplications reveals unexpected patterns of gene transcription and its regulation.

Ca2+ ions function as second messengers regulating many intracellular events, including neurotransmitter release, exocytosis, muscle contraction, metabolism and gene transcription. Cells of a multicellular organism express a variety of cell-surface receptors and channels that trigger an increase of the intracellular Ca2+ concentration upon stimulation. The elevated Ca2+ concentration is not uniformly distributed within the cytoplasm but is organized in subcellular microdomains with high and low concentrations of Ca2+ at different locations in the cell. Ca2+ ions are stored and released by intracellular organelles that change the concentration and distribution of Ca2+ ions. A major function of the rise in intracellular Ca2+ is the change of the genetic expression pattern of the cell via the activation of Ca2+-responsive transcription factors. It has been proposed that Ca2+-responsive transcription factors are differently affected by a rise in cytoplasmic versus nuclear Ca2+. Moreover, it has been suggested that the mode of entry determines whether an influx of Ca2+ leads to the stimulation of gene transcription. A rise in cytoplasmic Ca2+ induces an intracellular signaling cascade, involving the activation of the Ca2+/calmodulin-dependent protein phosphatase calcineurin and various protein kinases (protein kinase C, extracellular signal-regulated protein kinase, Ca2+/calmodulin-dependent protein kinases). In this review article, we discuss the concept of gene regulation via elevated Ca2+ concentration in the cytoplasm and the nucleus, the role of Ca2+ entry and the role of enzymes as signal transducers. We give particular emphasis to the regulation of gene transcription by calcineurin, linking protein dephosphorylation with Ca2+ signaling and gene expression.

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Role of B cells in the expression of genetic resistance to growth of Rous sarcoma in the chicken

European Journal of Immunology ◽

10.1002/eji.1830080216 ◽

1978 ◽

Vol 8 (2) ◽

pp. 147-149 ◽

Cited By ~ 6

Author(s):

R. A. McBride ◽

D. H. Watanabe ◽

L. W. Schierman

Keyword(s):

B Cells ◽

Genetic Resistance ◽

Rous Sarcoma

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Assessment of the Role of Activator Protein-1 on Transcription of the Mouse Steroidogenic Acute Regulatory Protein Gene

Molecular Endocrinology ◽

10.1210/me.2003-0223 ◽

2004 ◽

Vol 18 (3) ◽

pp. 558-573 ◽

Cited By ~ 52

Author(s):

Pulak R. Manna ◽

Darrell W. Eubank ◽

Douglas M. Stocco

Keyword(s):

Binding Site ◽

Gene Transcription ◽

Dna Sequences ◽

Regulatory Protein ◽

Activator Protein 1 ◽

Transcriptional Responses ◽

Activator Protein ◽

Steroidogenic Acute Regulatory ◽

Star Gene

Abstract cAMP-dependent mechanisms regulate the steroidogenic acute regulatory (StAR) protein even though its promoter lacks a consensus cAMP response-element (CRE, TGACGTCA). Transcriptional regulation of the StAR gene has been demonstrated to involve combinations of DNA sequences that provide recognition motifs for sequence-specific transcription factors. We recently identified and characterized three canonical 5′-CRE half-sites within the cAMP-responsive region (−151/−1 bp) of the mouse StAR gene. Among these CRE elements, the CRE2 half-site is analogous (TGACTGA) to an activator protein-1 (AP-1) sequence [TGA(C/G)TCA]; therefore, the role of the AP-1 transcription factor was explored in StAR gene transcription. Mutation in the AP-1 element demonstrated an approximately 50% decrease in StAR reporter activity. Using EMSA, oligonucleotide probes containing an AP-1 binding site were found to specifically bind to nuclear proteins obtained from mouse MA-10 Leydig and Y-1 adrenocortical tumor cells. The integrity of the sequence-specific AP-1 element in StAR gene transcription was assessed using the AP-1 family members, Fos (c-Fos, Fra-1, Fra-2, and Fos B) and Jun (c-Jun, Jun B, and Jun D), which demonstrated the involvement of Fos and Jun in StAR gene transcription to varying degrees. Disruption of the AP-1 binding site reversed the transcriptional responses seen with Fos and Jun. EMSA studies utilizing antibodies specific to Fos and Jun demonstrated the involvement of several AP-1 family proteins. Functional assessment of Fos and Jun was further demonstrated by transfecting antisense c-Fos, Fra-1, and dominant negative forms of Fos (A-Fos) and c-Jun (TAM-67) into MA-10 cells, which significantly (P < 0.01) repressed transcription of the StAR gene. Mutation of the AP-1 site in combination with mutations in other cis-elements resulted in a further decrease of StAR promoter activity, demonstrating a functional cooperation between these factors. Mammalian two-hybrid assays revealed high-affinity protein-protein interactions between c-Fos and c-Jun with steroidogenic factor 1, GATA-4, and CCAAT/enhancer binding protein-β. These findings demonstrate that Fos and Jun can bind to the TGACTGA element in the StAR promoter and provide novel insights into the mechanisms regulating StAR gene transcription.

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Role of Receptor Binding and Gene Transcription for Both of Stimulatory and Inhibitory Effects of Interleukin-1 In Pancreatic β-Cells

Autoimmunity ◽

10.3109/08916939209150319 ◽

1992 ◽

Vol 12 (2) ◽

pp. 127-133 ◽

Cited By ~ 13

Author(s):

Décio L. Eizirik ◽

Daniel E. Tracey ◽

Klaus Bendtzen ◽

Stellan Sandler

Keyword(s):

Gene Transcription ◽

Receptor Binding ◽

Interleukin 1 ◽

Inhibitory Effects ◽

Β Cells ◽

Pancreatic Β Cells

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Role of glucocorticoids in activation of hepatic PEPCK gene transcription during exercise

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1994.266.4.e560 ◽

1994 ◽

Vol 266 (4) ◽

pp. E560-E566 ◽

Cited By ~ 5

Author(s):

J. E. Friedman

Keyword(s):

Transgenic Mice ◽

Gene Transcription ◽

Phosphoenolpyruvate Carboxykinase ◽

Mrna Levels ◽

Camp Response Element ◽

Carbohydrate Diet ◽

High Carbohydrate ◽

Enhancer Binding Protein ◽

Response To Exercise

The objective of these studies was to determine the molecular basis for the activation of phosphoenolpyruvate carboxykinase (PEPCK) gene transcription during prolonged submaximal exercise. Mice were fed a high-carbohydrate diet for 1 wk and exercised continuously by swimming for up to 120 min. The level of hepatic PEPCK mRNA increased progressively during exercise, reaching 510% above control, whereas transcription of the PEPCK gene increased 1,000%, before decreasing to control levels within 60 min of recovery. In transgenic mice carrying a chimeric gene consisting of the PEPCK promoter linked to a reporter gene for bovine growth hormone (bGH), PEPCK(-460)-bGH, the level of hepatic bGH mRNA increased by 490% in response to exercise, similar to the increase in the expression of the native PEPCK gene. However, in transgenic mice with a deletion of the glucocorticoid regulatory unit, PEPCK(-355)-bGH, bGH mRNA did not increase above control values. In transgenic mice with a block mutation in adenosine 3',5'-cyclic monophosphate (cAMP) regulatory regions -90/-82 and -250/-234, PEPCK cAMP response element 1 (CRE-1)/P3(1)-bGH, exercise increased bGH mRNA 260% above controls. Adrenalectomy (Adx) had no effect on PEPCK mRNA levels in nonexercised mice, whereas in adrenalectomized (Adx)-exercised mice, PEPCK mRNA increased only 80% above basal, and, in Adx mice injected with dexamethasone, PEPCK mRNA increased with exercise 570% above controls. Exercise was also associated with a large increase in transcription of the gene for the transcription factor CCAAT/enhancer-binding protein beta (C/EBP-beta) and a smaller rise in transcription of c-jun gene, both of which returned to control levels during recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

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Epigenetic regulation by the menin pathway

Endocrine Related Cancer ◽

10.1530/erc-17-0298 ◽

2017 ◽

Vol 24 (10) ◽

pp. T147-T159 ◽

Cited By ~ 15

Author(s):

Zijie Feng ◽

Jian Ma ◽

Xianxin Hua

Keyword(s):

Transcription Factors ◽

Cell Signaling ◽

Signaling Pathways ◽

Gene Transcription ◽

Epigenetic Regulation ◽

Posttranslational Modifications ◽

Genetic Model ◽

Mirna Biogenesis ◽

Endocrine Organs

There is a trend of increasing prevalence of neuroendocrine tumors (NETs), and the inherited multiple endocrine neoplasia type 1 (MEN1) syndrome serves as a genetic model to investigate how NETs develop and the underlying mechanisms. Menin, encoded by the MEN1 gene, at least partly acts as a scaffold protein by interacting with multiple partners to regulate cellular homeostasis of various endocrine organs. Menin has multiple functions including regulation of several important signaling pathways by controlling gene transcription. Here, we focus on reviewing the recent progress in elucidating the key biochemical role of menin in epigenetic regulation of gene transcription and cell signaling, as well as posttranslational regulation of menin itself. In particular, we will review the progress in studying structural and functional interactions of menin with various histone modifiers and transcription factors such as MLL, PRMT5, SUV39H1 and other transcription factors including c-Myb and JunD. Moreover, the role of menin in regulating cell signaling pathways such as TGF-beta, Wnt and Hedgehog, as well as miRNA biogenesis and processing will be described. Further, the regulation of the MEN1 gene transcription, posttranslational modifications and stability of menin protein will be reviewed. These various modes of regulation by menin as well as regulation of menin by various biological factors broaden the view regarding how menin controls various biological processes in neuroendocrine organ homeostasis.

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