Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously reported the isolation of yeast mutants that seem to affect the function of certain autonomously replicating sequences (ARSs). These mutants are known as mcm for their defect in the maintenance of minichromosomes. We have now characterized in more detail one ARS-specific mutation, mcm1-1. This Mcm1 mutant has a second phenotype; MAT alpha mcm1-1 strains are sterile. MCM1 is non-allelic to other known alpha-specific sterile mutations and, unlike most genes required for mating, it is essential for growth. The alpha-specific sterile phenotype of the mcm1-1 mutant is manifested by its failure to produce a normal amount of the mating pheromone, alpha-factor. In addition, transcripts of the MF alpha 1 and STE3 genes, which encode the alpha-factor precursor and the alpha-factor receptor, respectively, are greatly reduced in this mutant. These and other properties of the mcm1-1 mutant suggest that the MCM1 protein may act as a transcriptional activator of alpha-specific genes. We have cloned, mapped and sequenced the wild-type and mutant alleles of MCM1, which is located on the right arm of chromosome XIII near LYS7. The MCM1 gene product is a protein of 286 amino acid residues and contains an unusual region in which 19 out of 20 residues are either aspartic or glutamic acid, followed by a series of glutamine tracts. MCM1 has striking homology to ARG80, a regulatory gene of the arginine metabolic pathway located about 700 base-pairs upstream from MCM1. A substitution of leucine for proline at amino acid position 97, immediately preceding the polyanionic region, was shown to be responsible for both the alpha-specific sterile and minichromosome-maintenance defective phenotypes of the mcm1-1 mutant.
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PMID:Saccharomyces cerevisiae protein involved in plasmid maintenance is necessary for mating of MAT alpha cells. 306 8

Some Ty1 transposable-element insertion mutations of Saccharomyces cerevisiae activate adjacent-gene expression. These Ty1-activated genes are regulated similarly to certain mating genes. This report shows that the MCM1 protein, which binds to several mating genes, also binds to a transcriptional regulatory sequence in Ty1. The binding of MCM1 to Ty1 correlates with the ability of its binding site to function as a component of the Ty1 transcriptional activator. This correlation supports the idea that MCM1 is important for Ty1-activated gene expression. At mating-gene promoters, MCM1 binds with coactivators or repressors such as STE12, alpha 1, or alpha 2. In contrast, MCM1 binds without these associated DNA-binding proteins at its site in Ty1. This finding suggests that its role in Ty1-mediated transcription is different from that at mating genes.
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PMID:MCM1 binds to a transcriptional control element in Ty1. 838 Feb 28

GAL4.estrogen receptor.VP16 (GAL4.ER.VP16), which contains the GAL4 DNA-binding domain, the human ER hormone binding (AF-2) domain, and the VP16 activation domain, functions as a hormone-dependent transcriptional activator in yeast (Louvion, J.-F., Havaux-Copf, B., and Picard, D. (1993) Gene (Amst.) 131, 129-134). Previously, we showed that this activator can remodel chromatin in yeast in a hormone-dependent manner. In this work, we show that a weakened VP16 activation domain in GAL4.ER.VP16 still allows hormone-dependent chromatin remodeling, but mutations in the AF-2 domain that abolish activity in the native ER also eliminate the ability of GAL4.ER.VP16 to activate transcription and to remodel chromatin. These findings suggest that an important role of the AF-2 domain in the native ER is to mask the activation potential of the AF-1 activation domain in the unliganded state; upon ligand activation, a conformational change releases AF-2-mediated repression and transcriptional activation ensues. We also show that the AF-2 domain, although inactive at simple promoters on its own in yeast, can enhance transcription by the MCM1 activator in hormone-dependent manner, consistent with its having a role in activation as well as repression in the native ER.
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PMID:Mutations in the AF-2/hormone-binding domain of the chimeric activator GAL4.estrogen receptor.VP16 inhibit hormone-dependent transcriptional activation and chromatin remodeling in yeast. 985 87

Serum response factor (SRF) is a key transcriptional activator of the c-fos gene and of muscle-specific gene expression. We have identified four forms of the SRF coding sequence, SRF-L (the previously identified form), SRF-M, SRF-S and SRF-I, that are produced by alternative splicing. The new forms of SRF lack regions of the C-terminal transactivation domain by splicing out of exon 5 (SRF-M), exons 4 and 5 (SRF-S) and exons 3, 4 and 5 (SRF-I). SRF-M is expressed at similar levels to SRF-L in differentiated vascular smooth-muscle cells and skeletal-muscle cells, whereas SRF-L is the predominant form in many other tissues. SRF-S expression is restricted to vascular smooth muscle and SRF-I expression is restricted to the embryo. Transfection of SRF-L and SRF-M into C(2)C(12) cells showed that both forms are transactivators of the promoter of the smooth-muscle-specific gene SM22alpha, whereas SRF-I acted as a dominant negative form of SRF.
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PMID:Four isoforms of serum response factor that increase or inhibit smooth-muscle-specific promoter activity. 1064

Prolonged serum deprivation induces a structurally and functionally contractile phenotype in about 1/6 of cultured airway myocytes, which exhibit morphological elongation and accumulate abundant contractile apparatus-associated proteins. We tested the hypothesis that transcriptional activation of genes encoding these proteins accounts for their accumulation during this phenotypic transition by measuring the transcriptional activities of the murine SM22 and human smooth muscle myosin heavy chain promoters during transient transfection in subconfluent, serum fed or 7 day serum-deprived cultured canine tracheal smooth muscle cells. Contrary to our expectation, SM22 and smooth muscle myosin heavy chain promoter activities (but not viral murine sarcoma virus-long terminal repeat promoter activity) were decreased in long term serum-deprived myocytes by at least 8-fold. Because serum response factor (SRF) is a required transcriptional activator of these and other smooth muscle-specific promoters, we evaluated the expression and function of SRF in subconfluent and long term serum-deprived cells. Whole cell SRF mRNA and protein were maintained at high levels in serum-deprived myocytes, but SRF transcription-promoting activity, nuclear SRF binding to consensus CArG sequences, and nuclear SRF protein were reduced. Furthermore, immunocytochemistry revealed extranuclear redistribution of SRF in serum-deprived myocytes; nuclear localization of SRF was restored after serum refeeding. These results uncover a novel mechanism for physiological control of smooth muscle-specific gene expression through extranuclear redistribution of SRF and consequent down-regulation of its transcription-promoting activity.
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PMID:Physiological control of smooth muscle-specific gene expression through regulated nuclear translocation of serum response factor. 1086 94

Transforming growth factor-beta induces a smooth muscle cell phenotype in undifferentiated mesenchymal cells. To elucidate the mechanism(s) of this phenotypic induction, we focused on the molecular regulation of smooth muscle-gamma-actin, whose expression is induced at late stages of smooth muscle differentiation and developmentally restricted to this lineage. Transforming growth factor-beta induced smooth muscle-gamma-actin protein, cytoskeletal localization, and mRNA expression in mesenchymal cells. Smooth muscle-gamma-actin promoter-luciferase reporter activity was enhanced by transforming growth factor-beta, and deletion analysis revealed that CArG box 2 in the promoter was necessary for this transcriptional activation. CArG motifs bind transcriptional activator serum response factor; gel shift analyses revealed increased binding of serum response factor-containing complexes to this site in response to transforming growth factor-beta, paralleled by increased serum response factor protein expression. Serum response factor expression was found to be up-regulated by transforming growth factor-beta via transcriptional activation of the gene and post-transcriptional regulation. Using mesenchymal cells stably transfected with wild type or dominant-negative serum response factor, we demonstrated that its expression is sufficient for induction of a smooth muscle phenotype in mesenchymal cells and is necessary for transforming growth factor-beta-mediated smooth muscle induction.
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PMID:Transforming growth factor-beta induction of smooth muscle cell phenotpye requires transcriptional and post-transcriptional control of serum response factor. 1174 73