The promoter of the human parathyroid hormone gene contains a functional cyclic AMP-response element

Rupp, Eva; Mayer, Hubert; Wingender, Edgar

doi:10.1093/nar/18.19.5677

Cited by 28 publications

(10 citation statements)

References 56 publications

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“…Nonspecific binding was determined from experiments in presence of 100-fold molar excess of unlabelled retinoic acid or with bacterial extracts free of receptor protein obtained from LC137xpGPl-2. Scatchard analysis was performed as described by Scatchard (1949).…”

Section: Retinoid Binding Assaymentioning

confidence: 99%

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Recombinant human retinoic acid receptor α

Keidel

Rupp

Szardenings

1992

European Journal of Biochemistry

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The human retinoic acid receptor u was expressed in Escherichia coli. The recombinant protein was found to be very unstable in several E. coli strains, probably due to proteolysis. Conditions were established to obtain reasonable amounts of active protein for ligand and DNA binding studies. The recombinant receptor showed the expected DNA binding activities in gel-retardation assays. Ligand binding properties were measured in a charcoal absorption assay. The dissociation constant for highly specific bound retinoic acid was found to be 0.67 nM. The affinity of several synthetic retinoids to thc recombinant protein was determined and compared to their biological activity. Some of the values presented here differ significantly from those published earlier for the receptor or its isolated hormonebinding domain.The nuclear receptors for retinoids play a major role in the regulation of genes involved in cell differentiation and growth. Their natural ligand, the vitamin A derivative alltrans-retinoic acid, has been reported to be a possible morphogen in the embryonic tissues of frogs and chicken.

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Section: Retinoid Binding Assaymentioning

confidence: 99%

“…Gel-retardation assays (Fried and Crothers, 1981) were performed as described earlier (Rupp et al, 1990). The painvise complementary oligonucleotides of the hormoneresponsive element of the human osteocalcin gene promoter, OC (Schiile et al, 1990) …”

Section: Gel-retardation Assaymentioning

confidence: 99%

Recombinant human retinoic acid receptor α

Keidel

Rupp

Szardenings

1992

European Journal of Biochemistry

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“…A major limitation to identifying such regulatory elements, or confirming their functional relevance, has been the lack of suitable parathyroid cell lines that faithfully represent the parathyroid chief cell phenotype, namely the ability to synthesize and secrete PTH, both at a basal level and in response to known physiological regulators such as 1, 25-dihydroxyvitamin D3 (1,25-(OH) 2 D 3 ) and ionic calcium. Previous examinations of the PTH promoter region have identified DNA response elements for the vitamin D receptor (24), calcium (25–27), cyclic-AMP (28) and a yet unknown transcription factor (29). Recent studies have identified conserved DNA elements in the immediate upstream PTH promoter region, which bind to transcription factors Sp1, Sp3 and nuclear factor-Y (30–32).…”

Section: Introductionmentioning

confidence: 99%

Tissue-specific regulatory regions of the PTH gene localized by novel chromosome 11 rearrangement breakpoints in a parathyroid adenoma

Mallya

Wu²,

Saria

et al. 2010

Journal of Bone and Mineral Research

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Parathyroid adenomas can contain clonal rearrangements of chromosome 11 that activate the cyclin D1 oncogene through juxtaposition with the PTH gene. Here we describe such a chromosomal rearrangement whose novel features provide clues to locating elusive cis-regulatory elements in the PTH gene and also expand the physical spectrum of pathogenetic breakpoints in the cyclin D1 gene region. Southern analyses of the parathyroid adenoma revealed rearrangement in the PTH gene locus. Analysis of rearranged DNA clones that contained the breakpoint, obtained by screening a tumor genomic library, pinpointed the breakpoint in the PTH locus at 3.3 kb upstream of the first exon. Accordingly, highly conserved distal elements of the PTH 5’ regulatory region were rearranged at the breakpoint approximately 450 kb upstream of the cyclin D1 oncogene, resulting in overexpression of cyclin D1 mRNA. Thus, PTH-cyclin D1 gene rearrangement breakpoints in parathyroid tumors can be located far from those previously recognized. In addition to expanding the molecular spectrum of pathogenetic chromosomal lesions in this disease, features of this specific rearrangement reinforce the existence of one or more novel cis-enhancer/regulatory elements for PTH gene expression and narrow their location to a 1.7kb DNA segment in the distal PTH promoter.

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“…A sequence that resembles the canonical CRE but deviates in one position in the center of the recognition motif is found at position 47. This element, shown to be functional and to confer cAMP-responsiveness, is also present in the rat, bovine and human PTH promoters (Rupp et al 1990). It could be speculated that the modest (approximately two-fold) effect of isoproterenol or forskolin on the promoter activity is due to the deviation from the consensus sequence (TGACGTCA) in the center of the putative CRE (TGACATCA).…”

Section: Discussionmentioning

confidence: 99%

The murine gene encoding parathyroid hormone: genomic organization, nucleotide sequence and transcriptional regulation

Tong²,

Hiou-Tim³

et al. 2002

Journal of Molecular Endocrinology

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The type 1 parathyroid hormone receptor (PTHR1) binds, with equal affinity, two ligands with distinct biological functions: PTH, the major peptide hormone controlling calcium homeostasis, and the paracrine factor, PTH-related peptide (PTHrP), a local regulator of cellular proliferation and differentiation. To clarify the complexity of possible interactions between two distinct ligands, PTH and PTHrP, and their common receptor in the intact organism, and to identify as yet unrecognized roles for PTH in normal physiology, we have cloned and characterized the structural organization, nucleotide sequence and transcriptional regulation of the murine gene encoding PTH. One recombinant clone isolated from a mouse genomic library contained 14 kb of DNA, encompassing the entire Pth gene. The transcriptional unit spans 3·2 kb of genomic DNA and, analogous to the human PTH gene, it is interrupted by two introns. The deduced mRNA encodes the 115-amino acid precursor, preproPTH. Comparison of the murine preproPTH sequence with other mammalian forms of the protein shows it to be highly conserved and to share limited structural similarity to PTHrP at the amino-terminal region, a domain critical for binding and activation of their common receptor. Putative binding motifs for the transcription factors sex-determining region Y gene product, transcriptional repressor CDP, hepatic nuclear factor 3β, GATA-binding factor 1, glucocorticoid receptor, SRY-related high mobility group box protein 5 and cAMP response element binding protein were identified in the 5′ flanking region of the Pth gene. When placed upstream of a reporter gene, these sequences failed to confer transcriptional regulation in response to 1,25(OH) 2 vitamin D 3 , but responded positively to the addition of isoproterenol and forskolin. Mutational analysis identified a cAMP-response element in the Pth promoter.

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The promoter of the human parathyroid hormone gene contains a functional cyclic AMP-response element

Cited by 28 publications

References 56 publications

Recombinant human retinoic acid receptor α

Recombinant human retinoic acid receptor α

Tissue-specific regulatory regions of the PTH gene localized by novel chromosome 11 rearrangement breakpoints in a parathyroid adenoma

The murine gene encoding parathyroid hormone: genomic organization, nucleotide sequence and transcriptional regulation

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