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

The aim of the present study was to analyze the functional importance for the parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor (PTHR1) gene P2 promoter activity of the putative proximal Myc-associated zinc finger protein (MAZ) site localized at position bp -45 to -39 bp, taking advantage of a G/A mutation identified at position -40 in the human sequence. Wild-type 'full-length' (1285P2) and truncated (760P2) promoter sequences were inserted upstream to the luciferase basic (pLucB) and enhancer (pLucE) reporter gene expression vectors. Transient transfections in osteoblast-like SaOS-2 cells and renal cells (RC.SV3A2) showed that the -40 G/A mutation significantly impaired transcriptional activity of wild-type 1285P2-pLucB and 760P2-pLucE promoter constructs. Further truncation of the P2 sequence demonstrated that the sequence -109/-37 bp was essential for promoter activity. Co-transfection with a MAZ expression vector did not modify the wild-type 1285P2-pLucB construct reporter activity but significantly increased 2-fold the mutated construction activity (P<0.05). Electrophoretic mobility shift assays using SaOS-2 nuclear extracts and a double-stranded DNA fragment encompassing the -45 to -39 putative MAZ site (ds-MAZ-oligo) disclosed two specific DNA-protein complexes. Complex II (fast moving) had a lower affinity for the mutated MAZ motif than for the wild-type MAZ motif while complex I (slow moving) had the same affinity for both wild-type or mutated MAZ sequences. Competition studies with Sp1 consensus oligonucleotide (ds-Sp1-oligo) markedly reduced complex I intensity, with a concomitant increase in that of complex II. Finally, ribonuclease protection assays showed that P2-specific PTHR1 mRNA transcript expression was significantly decreased in SaOS-2 cells transfected with ds-MAZ-oligo as compared with that for control (P<0.001) and ds-Sp1-oligo (P<0.05). Taken together, our studies suggest that the putative -45 to -39 MAZ-binding site regulates the constitutive activity of human PTHR1 P2 promoter.
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PMID:Functional importance of Myc-associated zinc finger protein for the human parathyroid hormone (PTH)/PTH-related peptide receptor-1 P2 promoter constitutive activity. 1476 95

Rat immune-associated nucleotide 4-like 1 (Ian4l1) encodes an antiapoptotic protein, which is essential for T-cell survival. A frameshift mutation at codon 85 in the biobreeding diabetes-prone (BBDP) rat is the cause of their life-long T-cell lymphopenia, which includes lack of regulatory T-cells--a prerequisite for spontaneous autoimmune destruction of their beta-cells. This study reports the identification of seven Ian4l1 mRNA variants. The genomic organization of the exons indicates three promoter regions. The promoter of two of the mRNAs was characterized. Rapid amplification of cDNA ends (RACE) and ribonuclease protection assay (RPA) demonstrated multiple transcription start sites (TSS) with two major sites. The localization of the core promoter and regulatory regions was identified by a luciferase assay of the 2.7-kb upstream of the TSS. The regulatory regions functioned similarly in two cell lines--one expressing Ian4l1 and one not expressing it. This indicates that the cell-specific expression is controlled by regions outside the 2.7-kb region, or by the chromatin structure or chromatin methylation level. The core promoter is TATA-less and initiator element-less, and contains putative binding sites for YY1, Sp1, and MED-1, the latter being an element believed to be important for transcription from TATA-less promoters.
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PMID:The antiapoptotic gene Ian4l1 in the rat: genomic organization and promoter characterization. 1547 97


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