Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P51532 (transcriptional activator)
6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The EWS gene, which maps to band q12 of human chromosome 22, is involved in a wide variety of human solid tumors including Ewing sarcoma, related primitive neuroectodermal tumors, malignant melanoma of soft parts and desmoplastic small round cell tumors. In these tumors, the EWS is fused to genes encoding transcriptional activators/repressors, like Fli-1 or erg or ATF 1 or wt1. To better understand the function of the EWS protein, we cloned the EWS cDNA. Sequence analysis of this cDNA revealed differential splicing involving two exons encoding 72 amino acids. Both alternatively spliced transcripts, EWS and EWS-b, are expressed in a variety of cells. Because EWS proteins contain putative conserved RNA binding motifs, we studied the RNA binding properties of the EWS protein. The EWS-b protein binds to RNA in vitro and, specifically, to poly G and poly U. The RNA binding activity was localized to the carboxy terminal 86 amino acids, which constitute RGG box. Thus the amino terminal domain of EWS (NTD-EWS), which is involved in chromosome translocation may regulate the specificity of RNA binding activity of EWS. An EWS-erg chimeric protein, which is found in Ewing's sarcoma cells, functions as a transcriptional activator. Mutational analysis of EWS-erg chimeric protein revealed that NTD-EWS functions as a regulatory domain for the transcriptional activation properties of EWS-erg chimeric protein.
...
PMID:The EWS gene, involved in Ewing family of tumors, malignant melanoma of soft parts and desmoplastic small round cell tumors, codes for an RNA binding protein with novel regulatory domains. 808 18

LBP-1 is a cellular protein which binds strongly to sequences around the human immunodeficiency virus type 1 (HIV-1) initiation site and weakly over the TATA box. We have previously shown that LBP-1 represses HIV-1 transcription by inhibiting the binding of TFIID to the TATA box. Four similar but distinct cDNAs encoding LBP-1 (LBP-1a, -b, -c, and -d) have been isolated. These are products of two related genes, and each gene encodes two alternatively spliced products. Comparison of the amino acid sequence of LBP-1 with entries in the available protein data bases revealed the identity of LBP-1c to alpha-CP2, an alpha-globin transcription factor. These proteins are also homologous to Drosophila melanogaster Elf-1/NTF-1, an essential transcriptional activator that functions during Drosophila embryogenesis. Three of the recombinant LBP-1 isoforms show DNA binding specificity identical to that of native LBP-1 and bind DNA as a multimer. In addition, antisera raised against recombinant LBP-1 recognize native LBP-1 from HeLa nuclear extract. Functional analyses in a cell-free transcription system demonstrate that recombinant LBP-1 specifically represses transcription from a wild-type HIV-1 template but not from an LBP-1 mutant template. Moreover, LBP-1 can function as an activator both in vivo and in vitro, depending on the promoter context. Interestingly, one isoform of LBP-1 which is missing the region of the Elf-1/NTF-1 homology is unable to bind DNA itself and, presumably through heteromer formation, inhibits binding of the other forms of LBP-1, suggesting that it may function as a dominant negative regulator.
...
PMID:Characterization of a family of related cellular transcription factors which can modulate human immunodeficiency virus type 1 transcription in vitro. 811 10

The ets oncogene superfamily codes for a family of transcriptional factors that are involved in gene regulation not only by autonomous DNA binding but also by indirect DNA binding through interaction with cellular factors. We have previously shown that a member of this superfamily, elk-1, is a sequence specific transcriptional activator, which forms a serum response factor (SRF) dependent ternary complex with serum response element (SRE) similar to p62TCF. We describe here an alternatively spliced variant of elk-1 named delta elk-1, which has lost the SRF interaction domain, negative regulatory DNA binding domain, and part of the elk-1 DNA binding domain. This variant elk-1 protein has lost the capacity to form a SRF dependent ternary complex with SRE and to activate fos transcription. Since this splice variant lacks part of the ets DNA binding domain, it binds to DNA with a specificity that is different from that of the full length elk-1 protein. Therefore differential splicing within the DNA binding and protein-protein interaction domains of transcriptional factors can generate proteins with modulated DNA binding specificities and transcriptional regulation. Thus it is conceivable that variant elk-1 might function by competing for some of the elk-1 target sequences (like SRE) and thereby block the transcriptional activation of fos by SRF and elk-1. Alternately, variant elk-1 protein may be the repressor, recruited by the SRE bound SRF for c-fos repression, or it may have an altogether different function. Therefore, elk-1 appears to fall in the category of genes that encode activators and repressors through the mechanism of differential splicing.
...
PMID:Delta elk-1, a variant of elk-1, fails to interact with the serum response factor and binds to DNA with modulated specificity. 841 10

Max (Myc-associated factor X) is a basic helix-loop-helix/leucine zipper protein that has been shown to play a central role in the functional activity of c-Myc as a transcriptional activator. Max potentiates the binding of Myc-Max heterodimers through its basic region to its specific E-box Myc site (EMS), enabling c-Myc to transactivate effectively. In addition to the alternatively spliced exon a, several naturally occurring forms of alternatively spliced max mRNAs have been reported, but variant protein products from these transcripts have not been detected. Using Western blot (immunoblot) and immunoprecipitation analysis, we have identified a variant form of Max protein (16 to 17 kDa), termed dMax, in detergent nuclear extracts of murine B-lymphoma cells, normal B lymphocytes, and NIH 3T3 fibroblasts. Cloning and sequencing revealed that dMax contains a deletion spanning the basic region and helix 1 and the loop of the helix-loop-helix region, presumably as a result of alternative splicing of max RNA. S1 nuclease analysis confirmed the presence of the mRNA for dMax in cells. The dMax protein, prepared via in vitro transcription and translation, associated with bacterially synthesized Myc-glutathione S-transferase. Coimmunoprecipitation of dMax and c-Myc indicated their intracellular association. In vitro-synthesized dMax failed to bind EMS DNA, presumably because of the absence of the basic region. Coexpression of dMax inhibited EMS-mediated transactivation by c-Myc. Thus dMax, which can interact with c-Myc, appears to function as a dominant negative regulator, providing an additional level of regulation to the transactivation potential of c-Myc.
...
PMID:Variant Max protein, derived by alternative splicing, associates with c-Myc in vivo and inhibits transactivation. 852 35

Nuclear respiratory factor 1 (nrf-1) is a transcriptional activator that is most probably essential in the regulation of mitochondrial biogenesis. In studies of the expression of the NRF-1 gene in cultured human fibroblasts, using RT-PCR, we identified two distinct transcripts, one of which contained an in-frame deletion of 198 bp. Analysis of genomic DNA by sequencing, showed that the shorter mRNA is the result of alternative splicing (exon skipping). The shorter transcript will result in an isoform of the protein that lacks the carboxy-terminal part of the DNA binding domain, which might influence transcriptional activation by normal nrf-1. The alternatively spliced transcript was also present in other human cell lines and in several human tissues. A quantitative PCR analysis showed that the percentages of the alternatively spliced transcript ranged from 3 to 17%. Differences in the percentage of alternatively spliced NRF-1 pre-mRNA may influence mitochondrial biogenesis under variable physiological conditions and could play a role in distinct mitochondrial diseases.
...
PMID:The pre-mRNA of nuclear respiratory factor 1, a regulator of mitochondrial biogenesis, is alternatively spliced in human tissues and cell lines. 854 44

mi-er1 (previously called er1) is a fibroblast growth factor-inducible early response gene activated during mesoderm induction in Xenopus embryos and encoding a nuclear protein that functions as a transcriptional activator. The human orthologue of mi-er1 was shown to be upregulated in breast carcinoma cell lines and breast tumours when compared to normal breast cells. In this report, we investigate the structure of the human mi-er1 (hmi-er1) gene and characterize the alternatively spliced transcripts and protein isoforms. hmi-er1 is a single copy gene located at 1p31.2 and spanning 63 kb. It contains 17 exons and includes one skipped exon, a facultative intron and three polyadenylation signals to produce 12 transcripts encoding six distinct proteins. hmi-er1 transcripts were expressed at very low levels in most human adult tissues and the mRNA isoform pattern varied with the tissue. The 12 transcripts encode proteins containing a common internal sequence with variable N- and C-termini. Three distinct N- and two distinct C-termini were identified, giving rise to six protein isoforms. The two C-termini differ significantly in size and sequence and arise from alternate use of a facultative intron to produce hMI-ER1alpha and hMI-ER1beta. In all tissues except testis, transcripts encoding the beta isoform were predominant. hMI-ER1alpha lacks the predicted nuclear localization signal and transfection assays revealed that, unlike hMI-ER1beta, it is not a nuclear protein, but remains in the cytoplasm. Our results demonstrate that alternate use of a facultative intron regulates the subcellular localization of hMI-ER1 proteins and this may have important implications for hMI-ER1 function.
...
PMID:Genomic organization of the human mi-er1 gene and characterization of alternatively spliced isoforms: regulated use of a facultative intron determines subcellular localization. 1224 14

The cAMP responsive transcriptional factor, CREB, is highly conserved among animal species, and its activity affects their behavior. In Drosophila melanogaster, one of alternatively spliced products of the CREB gene, dCREB2-a, is a transcriptional activator, while another isoform, dCREB2-b, is a repressor of dCREB2-a. Here, we demonstrate that overexpression of dCREB2-b in virgin females enhances their sexual receptivity. We studied the role of dCREB2 in female mating behavior using two transgenic lines, hs-dCREB2-a and hs-dCREB2-b, which overexpress respective products with heat-shock treatment. Wild-type males started their courtship behavior and mated more quickly with heat-shocked hs-dCREB2-b females than with non-heat-shocked hs-dCREB2-b females. Overexpression of dCREB2-a in females affected neither their courtship behavior nor mating frequency. The effects of overexpressed dCREB2-b were not due to elevated locomotor activities of heat-shocked females nor due to more vigorous courtship behavior of paired wild-type males. CREB might be involved in female sexual behavior of animals.
...
PMID:Overexpression of a CREB repressor isoform enhances the female sexual receptivity in Drosophila. 1246 39

The mixed lineage leukemia (MLL) gene at chromosome band 11q23 is commonly involved in reciprocal translocations that are detected in acute leukemias. Evidence suggests that the resulting MLL fusion genes contribute to leukemogenesis. AF9 is a common MLL fusion partner in acute myeloid leukemia. The AF9 protein functions as a transcriptional activator in artificial reporter gene assays and a structurally related protein in yeast, ANC1/TFG3, is a component of the SWI/SNF complex. Apart from these observations, little is known about the biologic function of AF9 in mammals. We have found that a recently described transcriptional repressor, BCL-6 corepressor (BCoR), interacts with the carboxy-terminus of AF9. The interaction of AF9 with BCoR has been confirmed by independent in vitro and in vivo protein-binding studies. The BCoR gene is expressed as several alternatively spliced transcripts. AF9 only binds BCoR isoforms that contain a unique 34 aa sequence located in the mid-portion of the protein. In artificial reporter gene assays, a BCoR isoform that binds AF9 efficiently suppresses AF9 transcriptional activity, while a nonbinding isoform does not. These results indicate that different isoforms of BCoR have unique biologic properties and that cell function may be partly determined by the different isoforms that are present within the cell.
...
PMID:The mixed lineage leukemia fusion partner AF9 binds specific isoforms of the BCL-6 corepressor. 1277 90

Sterol regulatory element-binding proteins (SREBPs) are a family of membrane-bound transcription factors that regulate cholesterol and fatty acid homeostasis. In mammals, three SREBP isoforms designated SREBP-1a, SREBP-1c, and SREBP-2 have been identified. SREBP-1a and SREBP-1c are derived from the same gene by virtue of alternatively spliced first exons. SREBP-1a has a longer transcriptional activation domain and is a more potent transcriptional activator than SREBP-1c in cultured cells and liver. Here, we describe the physiologic consequences of overexpressing the nuclear form of SREBP-1a (nSREBP-1a) in adipocytes of mice using the adipocyte-specific aP2 promoter (aP2-nSREBP-1a). The transgenic aP2-nSREBP-1a mice developed markedly enlarged white and brown adipocytes that were fully differentiated. Adipocytes isolated from aP2-nSREBP-1a mice had significantly increased rates of fatty acid synthesis and enhanced fatty acid secretion. The increased production and release of fatty acids from adipocytes led, in turn, to a fatty liver. Overexpression of the alternative SREBP-1 isoform, nSREBP-1c, in adipose tissue inhibits adipocyte differentiation; as a result, the transgenic nSREBP-1c mice develop a syndrome resembling human lipodystrophy, which includes a loss of peripheral white adipose tissue, diabetes, and fatty livers (Shimomura, I., Hammer, R. E., Richardson, J. A., Ikemoto, S., Bashmakov, Y., Goldstein, J. L., and Brown, M. S. (1998) Genes Dev. 12, 3182-3194). In striking contrast, nSREBP-1a overexpression in fat resulted in the hypertrophy of fully differentiated adipocytes, no diabetes, and mild hepatic steatosis. These results suggest that nSREBP-1a and nSREBP-1c have distinct roles in adipocyte fat metabolism in vivo.
...
PMID:Overexpression of sterol regulatory element-binding protein-1a in mouse adipose tissue produces adipocyte hypertrophy, increased fatty acid secretion, and fatty liver. 1285 91

We have cloned two novel, alternatively spliced messages of human cyclin D-binding Myb-like protein (hDMP1). The known, full-length protein has been named hDMP1alpha and the new isoforms, hDMP1beta and hDMP1gamma. The hDMP1alpha, -beta, and -gamma splice variants have unique expression patterns in normal hematopoietic cells; hDMP1beta mRNA transcripts are strongly expressed in quiescent CD34+ cells and freshly isolated peripheral blood leukocytes, as compared with hDMP1alpha. In contrast, activated T-cells and developing myeloid cells, macrophages, and granulocytes express low levels of hDMP1beta transcripts, and hDMP1gamma is ubiquitously and weakly expressed. Mouse Dmp1 has been shown to activate CD13/aminopeptidase N (APN) and p19ARF gene expression via binding to canonical DNA recognition sites in the respective promoters. Assessment of CD13/APN promoter responsiveness demonstrated that hDMP1alpha but not hDMP1beta and -gamma, is a transcriptional activator. Furthermore, hDMP1beta was found to inhibit the CD13/APN promoter transactivation ability of hDMP1alpha. Stable, ectopic expression of hDMP1beta and, to a lesser extent hDMP1gamma, reduced endogenous cell surface levels of CD13/APN in U937 cells. Moreover, stable, ectopic expression of hDMP1beta altered phorbol 12-myristate 13-acetate-induced terminal differentiation of U937 cells to macrophages and resulted in maintenance of proliferation. These results demonstrate that hDMP1beta antagonizes hDMP1alpha activity and suggest that cellular functions of hDMP1 may be regulated by cellular hDMP1 isoform levels.
...
PMID:Alternative splicing of the human cyclin D-binding Myb-like protein (hDMP1) yields a truncated protein isoform that alters macrophage differentiation patterns. 1291 99


1 2 Next >>

---