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

To identify the regions in the chicken c-myc promoter that are necessary for the binding of a nuclear trans-acting factor CTCF--the potential oncogene activator--we used a synthetic analog of the natural binding site that contains three correctly spaced CCCTC-repeats that are known to be involved in CTCF-binding. Gel retardation experiments failed to detect any CTCF-binding activity with this synthetic site. We conclude that GC-transversions made in the regions presumed to be invalid, do in fact interfere with the protein binding. The secondary structure analysis with S1-nuclease shows the presence of an unusual DNA conformation of the CTCF-binding site in the supercoiled plasmids, that can not be detected with the artificial construction. The precise mapping of S1 nuclease cleavage reveals several hypersensitive sites in the CCCTC-zone. Thus, an altered secondary structure may be functionally important for the protein recognition in vivo.
Mol Biol (Mosk)
PMID:[Regulatory protein factor CTCF interacts with a segment of the chicken c-myc oncogene promotor, capable of changing to a noncanonical conformation]. 179 97

In order to investigate further the mechanisms associated with growth inhibition of human breast cancer cells by progestins and nonsteroidal antiestrogens, their effect on c-myc gene expression in T-47D-5 and T-47D cells has been investigated. The c-myc mRNA levels were differentially regulated by the synthetic progestin, medroxyprogesterone acetate and the nonsteroidal antiestrogen, monohydroxytamoxifen, in both cell lines. Antiestrogen treatment caused a persistent decrease in c-myc mRNA levels while the progestin caused a more complex response. Initially c-myc mRNA levels increased approx. 2-fold, this was followed by a decrease and then partial recovery. The end result, however, of each of these treatments is decreased cell number.
J Steroid Biochem Mol Biol 1991 Jul
PMID:Differential regulation of c-myc by progestins and antiestrogens in T-47D human breast cancer cells. 182 55

The administration of the DNA topoisomerase II inhibitors 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) (10(-7) M), VP-16 (2 x 10(-7) M), or novobiocin (1.5 x 10(-4) M) reduces the growth activity of human promonocytic leukemia U-937 cells, by arresting them preferentially at the G2 (m-AMSA and VP-16) or at the G1 and G2 (novobiocin) phases of the cell cycle. Under these conditions, m-AMSA and VP-16 induce the differentiation of the cells efficiently, as proved both by an increase in the production of reactive oxygen species and by the activation of the surface expression of CD11b and CD11c, two differentiation-specific antigens. Novobiocin also induces the expression of those differentiation markers, but to a lesser extent. Analyses by Northern blot indicate that the topoisomerase II inhibitors reduce the levels of c-myc and beta-actin mRNA and increase the levels of vimentin mRNA. The expression of vimentin is also stimulated at the protein level, as indicated by immunofluorescence assays. This represents one of the few known instances in which topoisomerase inhibitors stimulate gene expression in eukaryotic cells.
Mol Pharmacol 1991 Apr
PMID:Differentiation of human promonocytic leukemia U-937 cells with DNA topoisomerase II inhibitors: induction of vimentin gene expression. 185 89

In vertebrate development, a prominent feature of several cell lineages is the coupling of cell cycle regulation with terminal differentiation. We have investigated the basis of this relationship in the skeletal muscle lineage by studying the effects of the proliferation-associated regulator, c-myc, on the differentiation of MyoD-initiated myoblasts. Transient cotransfection assays in NIH 3T3 cells using MyoD and c-myc expression vectors demonstrated c-myc suppression of MyoD-initiated differentiation. A stable cell system was also developed in which MyoD expression was constitutive, while myc levels could be elevated conditionally. Induction of this conditional c-myc suppressed myogenesis effectively, even in the presence of MyoD. c-myc suppression also prevented up-regulation of a relative of MyoD, myogenin, which is normally expressed at the onset of differentiation in all muscle cell lines examined and may be essential for differentiation. Additional experiments tested whether failure to differentiate in the presence of myc could be overcome by providing myogenin ectopically. Cotransfection of c-myc with myogenin, MyoD, or a mixture of myogenin and MyoD showed that neither myogenin alone nor myogenin plus MyoD together could bypass the c-myc block. The effects of c-myc were further dissected by showing that c-myc can inhibit differentiation independently of Id, a negative regulator of muscle differentiation. These results lead us to propose that c-myc and Id constitute independent negative regulators of muscle differentiation, while myogenin and any of the other three related myogenic factors (MyoD, Myf-5, and MRF4/herculin/Myf-6) act as positive regulators.
Mol Cell Biol 1991 May
PMID:c-myc inhibition of MyoD and myogenin-initiated myogenic differentiation. 185 Jan 5

Quiescent benzo[alpha]pyrene-transformed BALB/c 3T3 fibroblasts (line BP-A31), continue to express 'competence' genes (such as c-myc) and do not require platelet-derived growth factor ('competence' factor) in order to resume the cell division cycle. Insulin-like growth factor I (IGF-I), as well as insulin (at high concentrations, where it interacts with IGF-I-receptors) are potent mitogens in these cells. In contrast with the original non-transformed A31 cell line, we show that insulin/IGF-I (even in the absence of de novo protein synthesis) induce actin transcription in BP-A31 cells. We have verified that 'CArG' boxes, major actin promoter elements, can act as insulin-inducible elements in BP-A31 cells. Insulin-induced actin transcription is also observed in quiescent A31 cells stably transfected with a myc expression vector, suggesting a correlation between constitutive myc expression and insulin-induced actin transcription.
Mol Cell Endocrinol 1991 Mar
PMID:Insulin/insulin-like growth factor I induce actin transcription in mouse fibroblasts expressing constitutively myc gene. 185 Nov 11

Elevation of the steady-state mRNA levels of glucose transporter and c-myc are among the earliest changes in gene expression observed after Ha-rasT24 stimulation of Rat-1 fibroblasts to enter the cell cycle. Since the expression of these genes may be the result of either increased cell proliferation or a specific response to rasT24, we evaluated the expression of glucose transporter and c-myc and their induction during the cell cycle in both parental Rat-1 cells and cell lines bearing a metallothionein rasT24 fusion gene (MTrasT24). We showed that, although levels of glucose transporter and c-myc mRNAs in Rat-1 cells underwent a transient increase within hours of the addition of serum, epidermal growth factor, or 12-O-tetradecanoylphorbol-13-acetate to quiescent (G0) cells, the levels of glucose transporter and c-myc mRNA otherwise remained constant throughout the normal cell cycle. In cells carrying MTrasT24 (MR5 cells), induction of rasT24 expression by ZnSO4 led to a rapid induction of glucose transporter and c-myc mRNA expression in both quiescent (density-arrested) and G1/S-synchronized (aphidicolin-blocked) cells. These increases exceeded the constitutive levels expressed in rapidly proliferating Rat-1 cells, indicating that the ras oncogene has an effect on these genes that is independent of growth status. In addition, the transin gene, which is not expressed in proliferating Rat-1 cells in the continuous presence of serum growth factors, was also induced after increased expression of the mutant ras gene. These results suggest that the induction of glucose transporter, c-myc, and transin is the direct result of rasT24-mediated alterations in cellular gene expression and is distinct from normal cell-cycle events.
Mol Carcinog 1991
PMID:Elevation of glucose transporter, c-myc, and transin RNA levels by Ha-rasT24 is independent of its effect on the cell cycle. 187 50

Ubiquitously expressed transcription factors play an integral role in establishing and regulating patterns of gene transcription. Common factor 1 (CF1) is a ubiquitously expressed DNA-binding protein previously identified in our laboratory. We show here that CF1 recognizes sites in several diverse transcription elements, and we demonstrate the ability of the c-myc CF1 site to activate transcription of a basal promoter in both B cells and fibroblasts.
Mol Cell Biol 1991 Mar
PMID:Common factor 1 is a transcriptional activator which binds in the c-myc promoter, the skeletal alpha-actin promoter, and the immunoglobulin heavy-chain enhancer. 189 10

Interleukin-6 (IL-6) and leukemia inhibitory factor (LIF), two multifunctional cytokines, recently have been identified as physiological inducers of hematopoietic cell differentiation which also induce terminal differentiation and growth arrest of the myeloblastic leukemic M1 cell line. In this work, it is shown that c-myc exhibited a unique pattern of expression upon induction of M1 terminal differentiation by LIF or IL-6, with an early transient increase followed by a decrease to control levels by 12 h and no detectable c-myc mRNA by 1 day; in contrast, c-myb expression was rapidly suppressed, with no detectable c-myb mRNA by 12 h. Vectors containing the c-myc gene under control of the beta-actin gene promoter were transfected into M1 cells to obtain M1myc cell lines which constitutively synthesized c-myc. Deregulated and continued expression of c-myc blocked terminal differentiation induced by IL-6 or LIF at an intermediate stage in the progression from immature blasts to mature macrophages, precisely at the point in time when c-myc is normally suppressed, leading to intermediate-stage myeloid cells which continued to proliferate in the absence of c-myb expression.
Mol Cell Biol 1991 May
PMID:Interleukin-6- and leukemia inhibitory factor-induced terminal differentiation of myeloid leukemia cells is blocked at an intermediate stage by constitutive c-myc. 190 40

Transient expression of some proto-oncogenes, cytokines, and transcription factors occurs as a cellular response to growth factors, 12-O-tetradecanoylphorbol-13-acetate, antigen stimulation, or inflammation. Expression of these genes is mediated in part by the rapid turnover of their mRNAs. A + U-rich elements in the 3' untranslated regions of these mRNAs serve as one recognition signal targeting the mRNAs for rapid degradation. I report the identification of a cytosolic factor that both binds to the proto-oncogene c-myc A + U-rich element and specifically destabilizes c-myc mRNA in a cell-free mRNA decay system which reconstitutes mRNA decay processes found in cells. Proteinase K treatment of the factor abolishes its c-myc mRNA degradation activity without affecting its RNA-binding capacity. Thus, RNA substrate binding and degradation appear to be separable functions. These findings should aid in understanding how the cell selectively targets mRNAs for rapid turnover.
Mol Cell Biol 1991 May
PMID:An A + U-rich element RNA-binding factor regulates c-myc mRNA stability in vitro. 190 43

An AU-rich sequence present within the 3' untranslated region has been shown to mark some short-lived mRNAs for rapid degradation. We demonstrate by label transfer and gel shift experiments that a 32-kDa polypeptide, present in nuclear extracts, specifically interacts with the AU-rich domains present within the 3' untranslated region of human granulocyte-macrophage colony-stimulating factor, c-fos, and c-myc mRNAs and a similar domain downstream of the poly(A) addition site of the adenovirus IVa2 mRNA. Competition experiments and partial protease analysis indicated that the same polypeptide interacts with all four RNAs. A single AUUUA sequence in a U-rich context was sufficient to signal binding of the 32-kDa polypeptide. Insertion of three copies of this minimal recognition site led to markedly reduced accumulation of beta-globin RNA, while the same insert carrying a series of U-to-G changes had little effect on RNA levels. Steady-state levels of beta-globin-specific nuclear RNA, including incompletely processed RNA, and cytoplasmic mRNA were reduced. Cytoplasmic mRNA containing the AU-rich recognition sites for the 32-kDa polypeptide exhibited a half-life shorter than that of mRNA with a mutated insert. We suggest that binding of the 32-kDa polypeptide may be involved in the regulation of mRNA half-life.
Mol Cell Biol 1991 Jun
PMID:A 32-kilodalton protein binds to AU-rich domains in the 3' untranslated regions of rapidly degraded mRNAs. 190 42


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