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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of reporter genes under the control of upstream sequences of a human hsp70 gene was examined in microinjected Xenopus oocytes, transfected monkey COS and human HeLa cells. The genes were strictly heat-regulated in all three cell systems. A 69 nucleotide long segment of hsp70 5' non-transcribed sequence that included at least one functional heat shock regulation sequence was sufficient for heat-controlled expression in Xenopus and monkey cells but not in human HeLa cells. An additional segment of about 200 nucleotides in length was required for optimal activity. This segment contains two heat shock regulation elements, each of which appears to contribute to the overall activity in heat-treated human cells. Upstream non-transcribed sequences of the human hsp70 gene are capable of conferring heat regulation on a heterologous promoter. The potential roles in transcription regulation of a bending center in the TATA box region, a CCAAT-like sequence and some of many potential Sp1 binding sites in the hsp70 5' non-transcribed region were investigated.
J Mol Biol 1988 Sep 05
PMID:Cis-acting elements involved in the regulated expression of a human HSP70 gene. 318 91

The human 4F2 cell surface antigen is a 120-kilodalton (kDa) disulfide-linked heterodimer which is composed of an 80- to 90-kDa glycosylated heavy chain (4F2HC) and a 35- to 40-kDa nonglycosylated light chain (4F2LC). 4F2 belongs to a family of inducible cell surface molecules which are involved in T-lymphocyte activation and growth. To better understand the molecular mechanism(s) that controls 4F2HC gene expression in both resting and activated T cells, a 4F2HC human genomic clone was isolated and structurally characterized. The 4F2HC gene spans 8 kilobases of chromosome 11 and is composed of nine exons. The 5' upstream region of the gene displays several properties which are characteristic of housekeeping genes. It is G+C rich and hypomethylated in peripheral blood lymphocyte DNA and contains multiple binding sites for the Sp1 transcription factor while lacking TATA or CCAAT sequences. This region of the gene also displays sequence homologies with several other inducible T-cell genes, including the interleukin-2, interleukin-2 receptor alpha chain, dihydrofolate reductase, thymidine kinase, and transferrin receptor genes. A 255-base-pair fragment of the 4F2HC gene which contains 154 base pairs of the 5' flanking sequence was able to efficiently promote expression of the bacterial chloramphenicol acetyltransferase gene in human Jurkat T cells, indicating that it contains promoter or enhancer (or both) sequences. Analyses of chromatin structure in resting and lectin-activated T cells revealed the presence of stable DNase I-hypersensitive sites within both the 5' flanking and intron 1 regions of the 4F2HC gene. Although the 4F2HC gene displayed many of the structural features characteristic of a constitutively expressed gene, lectin-mediated activation of resting peripheral blood T lymphocytes resulted in a dramatic increase in steady-state levels of 4F2HC mRNA.
Mol Cell Biol 1988 Sep
PMID:Isolation and structural characterization of the human 4F2 heavy-chain gene, an inducible gene involved in T-lymphocyte activation. 326 70

We have characterized the cis-control signals in one of the two promoters of the developmentally regulated rat insulin-like growth factor II gene (rIGF-II) by a combination of in-vivo transient expression, in-vitro transcription, footprinting, gel band-shifting and methylation-interference experiments, using a series of deletion mutant templates. Our results indicate that this simple (minimal) promoter (P2) consists of no more than 128 base-pairs, which include an ATA box and four proximal upstream GC boxes binding the general transcription factor Sp1. Three of the latter sites deviate from the known Sp1 consensus recognition sequence. The two types of cis-acting regulatory signals (GC/ATA motif) of the P2 promoter are inter-dependent and sufficient for transcription. A model for the operation of this type of minimal promoter is discussed. S1 nuclease-hypersensitive sites, localized by in-vitro mapping to the region of the P2 Sp1-binding sites, are also present in vivo and correlate with the transcriptional state of chromatin in the rIGF-II locus. We show that recognition sites for Sp1 binding are a subset of sequences that exhibit hypersensitivity to S1.
J Mol Biol 1988 Jan 05
PMID:A promoter of the rat insulin-like growth factor II gene consists of minimal control elements. 335 24

Structural organization of the mouse mitochondrial malate dehydrogenase (EC 1.1.1.37) gene was determined by analyzing a genomic DNA fragment isolated from a cosmid library. The gene is 12,000 base-pairs long and contains nine exons interrupted by eight introns of various sizes. The 5' and 3'-flanking regions, and the exact sizes and boundaries of the exon blocks including the transcription-initiation sites were determined. In the 5'-flanking region, there is neither a TATA box nor a CAAT box. Instead of these sequences, there are six copies of the GGGCGG or CCGCCC sequence, which is a potential binding site for the transcription factor, Sp1. The 5'-flanking region up to about 600 nucleotides is G + C-rich (65%) and contains sequences compatible with the formation of a number of potentially stable stem-loop structures. S1 nuclease mapping and primer extension analysis demonstrated that transcription of the mitochondrial malate dehydrogenase gene initiates at multiple sites. Comparison of the nucleotide sequence of the promoter region of the mitochondrial malate dehydrogenase gene with that of the mitochondrial aspartate aminotransferase gene, revealed that there are several highly conserved regions between these two mitochondrial enzyme genes participating in the malate-aspartate shuttle.
J Mol Biol 1988 Mar 05
PMID:Structural organization of the mouse mitochondrial malate dehydrogenase gene. 337 35

We have cloned and characterized a mouse cytosolic aspartate aminotransferase (AspAT) (EC 2.6.1.1) gene, which is about 32,000 base-pairs long and is interrupted by eight introns. The 5' and 3'-flanking regions, and the exact sizes and boundaries of the exon blocks, including the transcription-initiation sites, were determined. The 5' end of the gene lacks the TATA and CAAT boxes characteristic of eukaryotic promoters, but contains G + C-rich sequences, three putative binding sites for a cellular transcription factor, Sp1, and multiple transcription-initiation sites. The sequences around the transcription-initiation sites are compatible with the formation of a number of potentially stable stem-loop structures. We compared the structural organization of the mouse cytosolic AspAT gene with that of the mouse mitochondrial AspAT gene, which has nine introns. We found that the promoter regions share a high level of homology and five of the introns are at identical places. This close matching leads to the tentative conclusion that the introns were in place before the divergence of cytosolic and mitochondrial isoenzyme genes.
J Mol Biol 1988 Mar 05
PMID:Structural organization of the mouse aspartate aminotransferase isoenzyme genes. Introns antedate the divergence of cytosolic and mitochondrial isoenzyme genes. 337 36

Using the technique of genomic footprinting, we demonstrate cadmium-inducible protection from dimethyl sulfate (DMS) modification of guanine residues in vivo in five metal-responsive elements (MREs) in the promoter of the rat metallothionein 1 (MT-1) gene. We also identify a site of extreme DMS hyperreactivity which, like the MRE protection, occurs only after metal ion induction. With this hyperreactive site as an indicator, we can measure the kinetics of induction and deinduction. Changes in the intracellular metal ion concentrations are reflected in alterations in the reactivity with DMS of guanine residues in the MT-1 gene promoter. Lastly, for both control and metal-induced cells, we observe DMS protection and enhancement of a binding site (located 5' of the distal MRE) which is a consensus sequence for the Sp1 transcription factor. Transfection experiments with deletion mutations of a fusion gene construct indicate both that a sequence region which includes this GC box regulates the basal level of expression of the MT-1 gene and that increasing the number of MREs in the promoter increases the induced level of transcription. Our genomic footprinting and transfection data together suggest that (i) a transcription factor, possibly Sp1, plays an important role in regulating the basal level of expression of the MT-1 gene and (ii) metal induction involves the metal-dependent binding to a sequence-specific binding factor which responds to changes in intracellular metal ion levels.
Mol Cell Biol 1987 Oct
PMID:Metal-dependent binding of a factor in vivo to the metal-responsive elements of the metallothionein 1 gene promoter. 368 94

The 5' end and promoter region of the alpha-subunit gene of chicken muscle acetylcholine receptor was mapped and sequenced. It includes a TATA and a CAAT box and a potential Sp1-binding site. When inserted in front of the chloramphenicol acetyltransferase gene, this promoter (including 850 base pairs of upstream sequence) directed high transient chloramphenicol acetyltransferase expression in transfected mouse C2.7 myotubes but not in C2.7 myoblasts or nonmyogenic 3T6 cells.
Mol Cell Biol 1987 Feb
PMID:A 5'-flanking region of the chicken acetylcholine receptor alpha-subunit gene confers tissue specificity and developmental control of expression in transfected cells. 382 34

The insulin-like growth factor I (IGF-I) receptor mediates signal transduction by the IGFs and plays a critical role in growth and development. The proximal promoter region of the rat IGF-I receptor gene contains multiple Sp1 consensus-binding sites (GC boxes). Various promoter fragments fused to a luciferase reporter gene were transiently cotransfected together with an Sp1 expression vector into Drosophila Schneider cells, which lack endogenous Sp1. A proximal promoter fragment containing 476 nucleotides of 5'-flanking region and 640 nucleotides of 5'-untranslated region was strongly activated by Sp1 (an average of 116-fold), and progressive 5'-deletions of the promoter that sequentially removed GC boxes reduced Sp1 activation to 15-fold over basal promoter activity. DNase I footprinting studies with purified Sp1 protein revealed four GC boxes in the 5'-flanking region of the promoter and one homopurine/homopyrimidine motif (CT element) in the 5'-untranslated region that bound Sp1. Mutation of the CT element reduced Sp1 activation by 70%. Taken together, these results demonstrate that Sp1 can regulate expression of the IGF-I receptor promoter by acting both on GC boxes in the 5'-flanking region of the promoter and on a CT element in the 5'-untranslated region.
Mol Endocrinol 1995 Sep
PMID:Regulation of insulin-like growth factor I receptor gene expression by Sp1: physical and functional interactions of Sp1 at GC boxes and at a CT element. 749 Nov 7

We describe the complete genomic organization of the rat insulin-like growth factor binding protein-2 (rIGFBP-2) gene. This single-copy gene spans over 36 kilobases (kb) and is split into four exons of 475, 224, 141, and 472 nucleotides (nt), and three introns of 32 kb, 686, and 1793 nt, respectively. A single transcription start site (-90) was mapped by S1 protection assay and primer extension. The putative promoter of the rIGFBP-2 gene does not possess TATA or CAAT elements; however, it contains three GC-rich regions located 37, 57, and 81 nt 5' of the cap site. Deletion analysis of the 0.6-kb region of the upstream sequences and transfection of these constructs into BRL-3A and Chinese hamster ovary cells were used to localize possible cis-acting elements. The three GC boxes enhanced chloramphenicol acetyltransferase and luciferase transcription almost to the same level as the XbaI-NsphI (-579 to +1) fragment and displayed synergism and orientation dependence. In addition a similar positive effect on luciferase transcription has been obtained by cotransfecting these fragments with varying amounts of Sp1 expression vector into Drosophila cells that lack endogenous Sp1. In vitro gel mobility shift assays demonstrated that box 1 (GGGCGG), box 2 (GGGAGG), and box 3 (GGGAAGG) bind to SpI with variable affinities and display cooperativity. A protein that gave a similar DNA binding pattern was present in nuclear extracts of BRL-3A cells. To analysis using consensus or aberrant Sp1 elements and a polyclonal Sp1 antiserum to inhibit DNA binding were performed. These in vivo and in vitro data demonstrated that Sp1 plays an important role in the regulation of the expression of rIGFBP-2.
Mol Endocrinol 1993 Sep
PMID:Genomic structure and regulation of the promoter of the rat insulin-like growth factor binding protein-2 gene. 750 79

The mouse CD40 ligand (CD40L) gene was cloned, sequenced and characterized. DNA sequence analysis showed that the CD40L gene comprises five exons and four intervening introns, spread over 13-14 kb of genomic DNA. The putative site for initiation of mRNA transcription was identified at 67 bp upstream of the translation initiation (ATG) codon. The nucleotide sequence of the 5'-flanking region of this gene revealed the presence of several regulatory regions including a TATA-like box, an Sp1-like box and six potential NF-AT-like motifs. The 3'-untranslated region of the murine CD40L gene contained two ATTTA-elements which are thought to confer instability to the mRNA of many cytokines and two adjacent dinucleotide repeates, (CT)25 and (CA)45. These elements may play a role in the post-transcriptional regulation of CD40L gene expression.
Mol Immunol 1994 Aug
PMID:Structure of the murine CD40 ligand gene. 752 May 29


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