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

The cellular proto-oncogene c-myc can acquire transforming potential by a number of different means, including retroviral transduction. The transduced allele generally contains point mutations relative to c-myc and is overexpressed in infected cells, usually as a v-Gag-Myc fusion protein. Upon synthesis, v-Gag-Myc enters the nucleus, forms complexes with its heterodimeric partner Max, and in this complex binds to DNA in a sequence-specific manner. To delineate the role for each of these events in fibroblast transformation, we introduced several mutations into the myc gene of the avian retrovirus MC29. We observed that Gag-Myc with a mutated nuclear localization signal is confined predominantly in the cytoplasm and only about 5% of the protein could be detected in the nucleus (less than the amount of endogenous c-Myc). Consequently, only a small fraction of Max is associated with Myc. However, cells infected with this mutant exhibit a completely transformed phenotype in vitro, suggesting that production of enough v-Gag-Myc to tie up all cellular Max is not needed for transformation. While the nuclear localization signal is dispensable for transformation, minimal changes in the v-Gag-Myc DNA-binding domain completely abolish its transforming potential, consistent with a role of Myc as a transcriptional regulator. One of its potential targets might be the endogenous c-myc, which is repressed in wild-type MC29-infected cells. Our experiments with MC29 mutants demonstrate that c-myc down-regulation depends on the integrity of the v-Myc DNA-binding domain and occurs at the RNA level. Hence, it is conceivable that v-Gag-Myc, either directly or circuitously, regulates c-myc transcription.
Mol Cell Biol 1993 Jun
PMID:Overproduction of v-Myc in the nucleus and its excess over Max are not required for avian fibroblast transformation. 849 74

Estrogen receptor positive ovarian cancer is often refractile to antiestrogen therapy. Here we describe the SKOV3 human ovarian carcinoma cell line as an in vitro model for estrogen and antiestrogen resistant ovarian cancer. While SKOV3 cells expressed estrogen receptor (ER) mRNA and protein at a similar level as the estrogen responsive T47D breast carcinoma cell line, their growth was not responsive to estradiol (E2) and was not inhibited by the antiestrogens OH-tamoxifen and ICI 164,384. The ER in SKOV3 cells was normal with respect to apparent Kd for binding with E2, E2 regulation of a transiently transfected ERE driven reporter gene, and E2 stimulation of expression of the early growth response genes c-myc and c-fos. However, the SKOV3 cells exhibited no expression of the progesterone receptor gene (PR) even after addition of E2, and the protein products of the estrogen responsive genes HER-2/neu and cathepsin D were expressed at constitutive levels that were not regulated by E2. Therefore, estrogen resistance in these cells may be a result of constitutive expression and loss of E2 regulation of selected growth regulatory gene products rather than a defect in estrogen activation of ER as a transcriptional regulator.
J Steroid Biochem Mol Biol 1995 Dec
PMID:SKOV3 ovarian carcinoma cells have functional estrogen receptor but are growth-resistant to estrogen and antiestrogens. 854 Dec 24

Mental handicap is a common clinical problem that has been a relatively neglected area of research. Though the causes are varied and complex, molecular biologists are making progress in understanding the mechanisms in some cases, particularly where there are distinguishing phenotypic or genetic markers. The fortuitous association of alpha thalassaemia with a form of mental retardation has allowed us to define a specific X-linked syndrome (ATR-X). Positional cloning was used to define a disease interval and examination of candidate genes demonstrated that mutations in a gene, XH2, showing homology to the SNF2 superfamily were responsible for this syndrome. The complex ATR-X phenotype suggests that this gene, when mutated, down-regulates the expression of several genes including the alpha-globin genes indicating that it could be a global transcriptional regulator. It is conceivable that this mechanism is involved in other forms of syndromal mental retardation.
Hum Mol Genet 1995
PMID:Syndromal mental retardation due to mutations in a regulator of gene expression. 854 68

The Cdc34 (Ubc3) ubiquitin-conjugating enzyme from Saccharomyces cerevisiae plays an essential role in the progression of cells from the G1 to S phase of the cell division cycle. Using a high-copy suppression strategy, we have identified a yeast gene (UBS1) whose elevated expression suppresses the conditional cell cycle defects associated with cdc34 mutations. The UBS1 gene encodes a 32.2-kDa protein of previously unknown function and is identical in sequence to a genomic open reading frame on chromosome II (GenBank accession number Z36034). Several lines of evidence described here indicate that Ubs1 functions as a general positive regulator of Cdc34 activity. First, overexpression of UBS1 suppresses not only the cell proliferation and morphological defects associated with cdc34 mutants but also the inability of cdc34 mutant cells to degrade the general amino acid biosynthesis transcriptional regulator, Gcn4. Second, deletion of the UBS1 gene profoundly accentuates the cell cycle defect when placed in combination with a cdc34 temperature-sensitive allele. Finally, a comparison of the Ubs1 and Cdc34 polypeptide sequences reveals two noncontiguous regions of similarity, which, when projected onto the three-dimensional structure of a ubiquitin-conjugating enzyme, define a single region situated on its surface. While cdc34 mutations corresponding to substitutions outside this region are suppressed by UBS1 overexpression, Ubs1 fails to suppress amino acid substitutions made within this region. Taken together with other findings, the allele specificity exhibited by UBS1 expression suggests that Ubs1 regulates Cdc34 by interaction or modification.
Mol Cell Biol 1996 Feb
PMID:Identification of a positive regulator of the cell cycle ubiquitin-conjugating enzyme Cdc34 (Ubc3). 855 96

The Schizosaccharomyces pombe pcr1 gene encodes a bZIP protein that apparently belongs to the cyclic AMP response element (CRE)-binding protein/activating transcription factor family. The deduced pcr1 gene product consists of 171 amino acid residues and is most similar to the mammalian CRE-BP1. A glutathione S-transferase-Pcr1 fusion protein produced in Escherichia coli was able to bind specifically to the CRE motif in vitro. Analysis with anti-Pcr1 serum suggested that Pcr1 is included in the major CRE-binding factors present in the S. pombe cell extract. Disruption of the pcr1 gene was not lethal, but the disruptant showed cold-sensitive growth on rich medium. The disruptant was also inefficient in mating and sporulation, though it was not completely sterile. Expression of the ste11 gene, which encodes a key transcription factor for sexual development, was greatly reduced in the disruptant, and overexpression of ste11+ suppressed the deficiency of the pcr1 disruptant in sexual development. It has been shown that expression of ste11 is negatively regulated by cyclic AMP-dependent protein kinase (PKA) and that the loss of PKA activity results in ectopic sexual development. Disruption of pcr1 blocked ectopic sexual development. Furthermore, disruption of pcr1 reduced expression of fbp1, a glucose-repressible gene negatively regulated by PKA. These results suggest that Pcr1 is a putative transcriptional regulator whose activity may be controlled by PKA. Alternatively, its activity may be independent of PKA, and full induction of ste11 and fbp1 expression requires the function of Pcr1 in addition to elimination of the repression by PKA.
Mol Cell Biol 1996 Feb
PMID:Schizosaccharomyces pombe pcr1+ encodes a CREB/ATF protein involved in regulation of gene expression for sexual development. 855 99

OmpR, the transcriptional regulator of the ompF and ompC porin genes, is a member of a novel class of DNA-binding proteins. The mechanism(s) by which this class of proteins interacts with target DNA sites is not understood. To address this issue, we investigated the nature of the DNA sequences recognized by OmpR. A 36 bp DNA fragment was identified that is capable of supporting OmpR-DNA interaction in vivo. The base pairs within this region of DNA that are critical to this interaction were identified by isolating mutations within the fragment that hinder normal OmpR-DNA binding. The results obtained provide insights concerning the nature of the sequences recognized by OmpR and also support a model in which co-operative binding is involved in OmpR-DNA interaction.
Mol Microbiol 1995 Aug
PMID:Identification of base pairs important for OmpR-DNA interaction. 855 75

AbrB is a global transcriptional regulator of many genes that are expressed as Bacillus subtilis exits from active growth into stationary phase and sporulation. Previous results have suggested that binding of abrB at some promoters involves multiple sites of recognition and is a cooperative process. It is shown here that the binding site at spoOE can be subdivided into 5' and 3' halves, each capable of directing AbrB binding. In addition, the central portion of the intact site can promote AbrB binding. Examination of various heterologous and homologous tandem combinations of the half-sites confirms that the native site is a complex array of overlapping suboptimal sites, the precise arrangement of which is required for optimal AbrB binding. Other data suggest that binding of multiple AbrB units is needed for stable complex formation. A binding mechanism involving numerous steps of intermediate affinity is envisioned.
Mol Gen Genet 1996 Apr 10
PMID:Dissection of the Bacillus subtilis spoOE binding site for the global regulator AbrB reveals smaller recognition elements. 862 35

We cloned the Schizosaccharomyces pombe map1 gene by virtue of its ability to stimulate transcription of the sxa2 gene, which encodes a carboxypeptidase expressed specifically in h- cells in response to mating-pheromone signaling. The cloned gene had a coding capacity of 398 amino acids split by two introns, and the deduced product was a protein of the MADS box family. This gene was most similar to Saccharomyces cerevisiae MCM1, which regulates cell-type-specific gene expression in budding yeast cells. Disruption of the S. pombe gene did not affect vegetative cell growth but conferred sterility. It blocked the mating ability of h+ cells completely and that of h- cells partially. Genetic and sequencing analysis indicated that the cloned gene is map1], which was originally defined by a mutation that caused h+-speciftic sterility. Northern (RNA) blot analysis showed that the function of map1 is absolutely essential for the expression of h+-specific genes and is required for the full activation of h--specific gene expression. Overexpression of map1 resulted in enhanced transcription of cell-type-specilic genes, but the range of genes affected by Map1 was restricted by the mating type of the cell. Results of yeast two-hybrid analysis suggested that Map1 may physically interact with Mat1-Pc, the product of the h(+)-specific mating-type gene mat1-Pc. On the basis of these observations, we speculate that Map1 may be a transcriptional regulator of cell-type-specific genes similar to S. cerevisiae MCM1, whose activity is modulated by the oil and alpha2 mating-type gene products.
Mol Cell Biol 1996 Jul
PMID:Schizosaccharomyces pombe map1+ encodes a MADS-box-family protein required for cell-type-specific gene expression. 866 57

Recently, the neurohormone melatonin was found to be a potent endogenous hydroxyl radical scavenger. Since the activation of an important transcriptional regulator, nuclear factor-kappa B (NF-kappa B) involves free radicals as second messengers, we investigated whether melatonin alters NF-kappa B expression if present during treatment of HeLa S3 cells with known activators. The results show that upon treatment of HeLa S3 cells with tumor necrosis factor-alpha or phorbol 12-myristate 13-acetate, or with ionizing radiation, there is a profound induction of NF-kappa B binding activity. If present at the time of treatment, exogenously added melatonin, at a concentration as low as 10 microM, was found to inhibit the activation of NF-kappa B by these agents. This results leads to the hypothesis that melatonin can play a role in many physiological functions through its modulation of NF-kappa B (and possibly other) transcriptional regulators.
Biochem Mol Biol Int 1995 Dec
PMID:The neurohormone melatonin inhibits cytokine, mitogen and ionizing radiation induced NF-kappa B. 874 36

The product of the Escherichia coli aidB gene is homologous to human isovaleryl-coenzyme A dehydrogenase (IVD), an enzyme involved in the breakdown of the amino acid leucine. The aidB gene is not expressed constitutively, but its transcription is induced via distinct mechanisms in response to: (i) exposure to alkylating agents; (ii) acetate at a slightly acidic pH; and (iii) anoxia. Induction by alkylating agents is mediated by the transcriptional activator Ada, in its methylated form (meAda); the other forms of induction are Ada independent and require sigma s, the alternative sigma factor mainly expressed during the stationary phase of bacterial growth. In this report we show that, in the absence of any transcriptional factor, aidB is efficiently transcribed in vitro by the sigma s, but not by the sigma 70, form of RNA polymerase holoenzyme. In the presence of meAda, levels of transcription by both forms of RNA polymerase are significantly increased. However, sigma s-dependent transcription of aidB is inhibited both in vitro and in vivo by binding of the transcriptional regulator Lrp (leucine responsive protein) to the aidB promoter region (PaidB). Lrp acts as a specific repressor for sigma s-dependent transcription of aidB. Leucine counteracts Lrp binding to P aidB, as does binding to P aidB of me Ada, which causes Lrp to dissociate from the promoter. The physiological significance of aidB transcription regulation is discussed.
Mol Microbiol 1996 Jun
PMID:The leucine-responsive regulatory protein (Lrp) acts as a specific repressor for sigma s-dependent transcription of the Escherichia coli aidB gene. 880 48


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