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

c-myb is expressed predominantly in proliferating immature hemopoietic cells and, like v-myb, functions as a transcriptional activator that displays sequence-specific DNA binding. Oncogenic activation of the c-myb protein (Myb) is associated with carboxyl-terminal and/or amino-terminal truncations, the former of which also potentiates Myb's transcriptional activation capacity. We show here that a carboxyl-truncated Myb protein binds with a 7-fold higher affinity to an oligonucleotide bearing a Myb recognition sequence than does the full-length form. In addition, data are presented which show that Myb binds with different apparent affinities to variants of the recognition site and that Myb binds independently to adjacent sites regardless of the orientation of these sites.
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PMID:Interaction of the Myb protein with specific DNA binding sites. 154 39

Oncogenic forms of the c-myb protein (Myb) often exhibit amino-terminal and/or carboxyl-terminal truncations. When the transcriptional activity of these proteins was examined it was found that carboxyl-truncated Myb is more effective as a transcriptional activator than full-length or amino-truncated Myb. In order to determine the effect of such truncations on sequence-specific DNA binding, we synthesized murine Myb in vitro and assessed DNA binding by using a mobility-shift assay. Compared with the full-length protein no difference in binding was observed following deletion of the amino terminus, despite the removal of much of the first repeat of the DNA-binding domain. However, the specific DNA-binding capacity of carboxyl-truncated Myb was 4-6 times greater than that of the full-length protein; moreover, DNA binding was independent of a 'leucine zipper' motif present in Myb. These observations suggest that the increased transforming and transactivating potential of carboxyl-truncated Myb is due, at least in part, to increased sequence-specific DNA binding.
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PMID:Increase in specific DNA binding by carboxyl truncation suggests a mechanism for activation of Myb. 192 10

The human c-myb proto-oncogene is the cellular progenitor of the viral v-myb oncogene and codes for a 75 kD protein involved in growth regulation and differentiation in a number of cells. Fusion proteins in which human c-myb sequences are linked to the DNA binding domain of the yeast transcriptional activator GAL4 can activate transcription from a reporter gene which carries the chloramphenicol acetyl transferase (CAT) gene linked in cis to a repeat of the GAL4 binding site. Deletions of carboxyterminal sequences allowed the identification of the domain responsible for transcriptional activation, which is located between amino acid residues 275 to 327. Deletion of this activator domain results in abrogation of the transcriptional activation. The GAL4-v-myb fusion protein can also activate transcription whereas no transactivation by GAL4-c-myb is observed, indicating that a carboxyterminal domain of c-myb which is absent from v-myb apparently negatively regulates transcriptional activation. Dimer formation which is required for transactivation by GAL4 fusion proteins can, when GAL4 is truncated, be mediated by a region of the c-myb protein upstream of the transactivator domain possibly including the transactivator domain itself but not a putative leucine zipper located downstream of this region.
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PMID:Transcriptional activation by human c-myb and v-myb genes. 218 2

C-myb encodes a transcriptional activator that is essential for the development of the hematopoietic system but appears to lack major roles in non-hematopoietic cells. The identification of two conserved myb-related genes, designated A-myb and B-myb, has raised the possibility that these genes are functional equivalents of c-myb in non-hematopoietic cells. Here, we report the isolation and preliminary characterization of the mouse A-myb gene. Mouse A-myb maps to the proximal region of chromosome 1 and encodes a transcriptional activator with properties similar to those of the c-myb and v-myb proteins. During embryo-genesis A-myb is predominantly expressed in several regions of the developing central nervous system (CNS) and the urogenital ridge. Expression in the CNS is confined to the neural tube, the hindbrain, the neural retina and the olfactory epithelium, and coincides with the presence of proliferating immature neuronal precursor cells. In the adult mouse, A-myb is expressed during the early stages of sperm cell differentiation and in B lymphocytes located in germinal centers of the spleen. Taken together, these results suggest a role for A-myb in the proliferation and/or differentiation of neurogenic, spermatogenic and B-lymphoid cells.
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PMID:Mouse A-myb encodes a trans-activator and is expressed in mitotically active cells of the developing central nervous system, adult testis and B lymphocytes. 781 37

The retroviral oncogene v-myb encodes a transcriptional activator which is responsible for the activation of the mim-1 gene in myelomonocytic cells transformed by v-myb. The mim-1 promoter contains several myb consensus binding sites and has previously been shown to be regulated directly by v-myb. Here we report that the mim-1 gene is activated synergistically by v-myb and different C/EBP transcription factors. We have cloned a chicken C/EBP-related gene that is highly expressed in myeloid cells and identified it as the chicken homolog of C/EBP beta. A dominant-negative variant of chicken C/EBP beta interferes with the v-myb induced activation of the mim-1 gene in these cells, suggesting that C/EBP beta or another C/EBP transcription factor is required for the activation of mim-1 by v-myb. We found that C/EBP beta and other C/EBP transcription factors confer to fibroblasts the ability to induce the mim-1 gene in the presence of v-myb. Finally we show that, in contrast to v-myb, c-myb synergizes with C/EBP transcription factors only at low concentrations of c-myb protein. Our results suggest a role for C/EBP beta, and possibly for other C/EBP transcription factors, in v-myb function and in myeloid-specific gene activation.
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PMID:Synergistic activation of the chicken mim-1 gene by v-myb and C/EBP transcription factors. 849 Nov 93

C/EBPepsilon is essential for granulocytic differentiation. We investigated the role of C/EBPepsilon in the transcriptional activation of various myeloid-specific genes. We found that two C/EBPepsilon isoforms, p32 and p30, possessing transcriptional activation domains were coexpressed in myeloid cells. Interestingly, isoform C/EBPepsilon p30 but not p32 was differentially upregulated in NB-4 promyelocytic leukemia cells treated with retinoids. Both isoforms bound specifically to C/EBP sites in myeloid promoters. The kd for C/EBPepsilon binding to the C/EBP site of the neutrophil elastase promoter was 4.2 nmol/L. In transfection assays using the nonhematopoietic cell line, CV-1, the p32 isoform activated promoters from the myeloid-specific mim-1, neutrophil elastase, and granulocyte colony-stimulating factor (G-CSF) receptor genes by 2.5-, 1.8-, and 1.6-fold, respectively. The p30 isoform lacked significant transcriptional activity, suggesting that other hematopoietic-specific factors were required for its function. Consistent with this prediction, transfections into the hematopoietic cell line Jurkat showed a 9.0- and 2.5-fold activation of the mim-1 promoter by the p32 and p30 isoforms, respectively. The additional 32 NH2-terminal residues made p32 a significantly more potent transcriptional activator than p30. T lymphoblasts (Jurkat cells) and immature myeloid cells (eg, Kcl22 cells) expressed high levels of the c-myb hematopoietic transcription factor. Cotransfection of c-myb with either the p32 or p30 isoform of C/EBPepsilon in CV-1 cells cooperatively transactivated the mim-1 promoter by 20- and 16-fold, respectively, and the neutrophil elastase promoter by 10-and 7-fold, respectively. Pulldown assays showed that each C/EBPepsilon isoform interacted directly with the DNA binding domain of the c-myb protein. Further studies showed that Kcl22 myeloid cells only contained active C/EBPepsilon, but not C/EBPalpha, C/EBPbeta, or C/EBPdelta. A mutation of the C/EBP site in the neutrophil elastase promoter markedly decreased the transactivation of the promoter in Kcl22 myeloblasts. These results demonstrate a role for C/EBPepsilon in regulating myeloid promoters, such as neutrophil elastase, probably through a direct interaction with c-myb.
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PMID:C/EBPepsilon directly interacts with the DNA binding domain of c-myb and cooperatively activates transcription of myeloid promoters. 1023 85