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

Notch signaling commences with two ligand-mediated proteolysis events that release the Notch intracellular domain, NICD, from the plasma membrane. NICD then translocates into the nucleus and interacts with the DNA binding protein CSL to activate transcription. We found that NICD expression also potentiates activity of the transcription factor LEF-1. NICD stimulation of LEF-1 activity was context dependent and occurred on a subset of promoters distinct from those activated by beta-catenin. Importantly, the effect of NICD does not appear to be mediated through canonical components of the Wnt signaling pathway or downstream components of the Notch pathway. In vitro assays show a weak association between the C-terminal transactivation domain of NICD and the high-mobility group domain of LEF-1, suggesting that the two proteins interact in vivo. Our data therefore describe a new nuclear target of Notch signaling and a new coactivator for LEF-1.
Mol Cell Biol 2001 Nov
PMID:The notch intracellular domain can function as a coactivator for LEF-1. 1160 90

Insulators define chromosomal domains such that an enhancer in one domain cannot activate a promoter in a different domain. We show that the Drosophila gypsy insulator behaves as a cis-stimulatory element in the larval fat body. Transcriptional stimulation by the insulator is distance dependent, as expected for a promoter element as opposed to an enhancer. Stimulation of a test alcohol dehydrogenase promoter requires a binding site for a GATA transcription factor, suggesting that the insulator may be facilitating access of this DNA binding protein to the promoter. Short-range stimulation requires both the Suppressor of Hairy-wing protein and the Mod(mdg4)-62.7 protein encoded by the trithorax group gene mod(mdg4). In the absence of interaction with Mod(mdg4)-62.7, the insulator is converted into a short-range transcriptional repressor but retains some cis-stimulatory activity over longer distances. These results indicate that insulator and promoter sequences share important characteristics and are not entirely distinct. We propose that the gypsy insulator can function as a promoter element and may be analogous to promoter-proximal regulatory modules that integrate input from multiple distal enhancer sequences.
Mol Cell Biol 2001 Nov
PMID:The gypsy insulator can act as a promoter-specific transcriptional stimulator. 1160 7

Notch-1 belongs to a family of transmembrane receptor proteins that direct the decisions as to various cell fates. After ligand binding, a proteolytic cleavage step occurs and the intracellular part of Notch-1, Notch-1-IC, translocates into the nucleus, where it targets the DNA binding protein RBP-J kappa/CBF1. RBP-J kappa mediates repression through recruitment of a histone deacetylase-containing complex. The Notch-1-IC/RBP-J kappa complex overcomes repression and activates the transcription of Notch target genes. We have identified a novel domain in Notch-1-IC, the EP domain, which is indispensable for full transcriptional activation. This transactivation domain is localized adjacent to the ankyrin repeats of Notch-1-IC. In cotransfection experiments, Notch-1-IC-mediated transcriptional activation was inhibited by E1A12S and p53, two proteins, which interfere with the function of the common coactivator p300. Protein-protein interaction assays demonstrated the association of Notch-1-IC and the CH3 region of p300. In addition, the interaction of mammalian Notch-1-IC with p300 was destabilized after deletion of the EP domain of Notch-1-IC. Based on physical interaction with Notch-1-IC and coactivator functions of p300, we propose a model for Notch-1-mediated gene regulation via p300.
Mol Cell Biol 2001 Nov
PMID:p300 acts as a transcriptional coactivator for mammalian Notch-1. 1160 11

Molecules derived from the neural tube and found in chick embryo extract (CEE) and bone morphogenetic proteins (BMP) support the differentiation of neural crest-derived catecholaminergic (CA) neurons. We now report that intracellular signaling resulting in the activation of Map kinase (MapK) or translocation of Smad1 mediate the differentiation of CA neurons in response to CEE or BMP 4, respectively. The differentiation of CA neurons was significantly reduced by inhibiting MapK using PD98059 or by pan-specific blockade of tyrosine kinases using Herbimycin A. In the presence of BMP 4 and inhibitors of MapK signaling, differentiation of CA neurons was only moderately reduced. Independent of MapK, BMP 4 induced translocation of Smad1 from the cytosol to the nucleus and induced transcription of dHAND, a DNA binding protein required for the differentiation of CA neurons. The data suggest that CEE-derived factors and BMP4 support the differentiation of CA neurons via independent signaling pathways.
Mol Cell Neurosci 2001 Oct
PMID:Two signal transduction pathways involved in the catecholaminergic differentiation of avian neural crest-derived cells in vitro. 1164 Aug 96

The oligomeric "sliding clamp" processivity factors, such as PCNA, are thought to rely on a loose, topological association with DNA to slide freely along dsDNA. Unlike PCNA, the processivity subunit of the herpes simplex virus DNA polymerase, UL42, is a monomer and has an intrinsic affinity for dsDNA that is remarkably high for a sequence-independent DNA binding protein. Using a DNase footprinting assay, we demonstrate that UL42 translocates with the catalytic subunit of the polymerase during chain elongation. In addition, footprinting and electrophoretic mobility shift assays show that, despite its tight DNA binding, UL42 is capable of linear diffusion on DNA at a rate of between 17 and 47 bp/s. Our results thus suggest that, despite profound biochemical differences with the sliding clamps, UL42 can freely slide downstream with the catalytic subunit during DNA replication.
Mol Cell 2001 Oct
PMID:Linear diffusion on DNA despite high-affinity binding by a DNA polymerase processivity factor. 1168 25

Studies have clearly demonstrated that DNA itself is not or scarcely immunogenic in experimental animals. We have previously demonstrated that linking human polyomavirus large T-antigen to DNA rendered DNA immunogenic irrespective of the source or the structure of DNA. As an alternative to this artificial system, in vivo expression of the DNA binding protein large T-antigen of human polyomaviruses also resulted in the production of anti-DNA antibodies. This observation demonstrates that the large T-antigen concept is operational in vivo and supports the idea that complex formation between a non-self DNA-binding protein and DNA renders DNA immunogenic in analogy to a hapten-carrier model. To further investigate this model, the DNA binding domain (DBD) of a self-protein (glucocorticoid receptor) was linked to a non-DNA binding non-self protein, the green fluorescent protein (GFP). Immunization of mice with an expression plasmid for this fusion protein resulted in the production of anti-DNA antibodies, while mice inoculated with either a plasmid encoding the GFP or a plasmid encoding the DBD of the glucocorticoid receptor failed to produce anti-DNA antibodies. These results demonstrate that DNA may become immunogenic through in vivo association with any non-self DNA binding protein. Considering these data in context of results obtained with the polyomavirus large T-antigen, one may conclude that viral DNA-binding proteins may affect the regulation of immune tolerance to DNA and nucleosomes in vivo.
Mol Immunol 2002 Jan
PMID:Green fluorescent protein modified to bind DNA initiates production of anti-DNA antibodies when expressed in vivo. 1175 Jun 52

Autonomously replicating sequence-binding factor 1 (ABF1) is a multifunctional, site-specific DNA binding protein that is essential for cell viability in Saccharomyces cerevisiae. ABF1 plays a direct role in transcriptional activation, stimulation of DNA replication, and gene silencing at the mating-type loci. Here we demonstrate that all three activities of ABF1 are conferred by the C terminus of the protein (amino acids [aa] 604 to 731). Furthermore, a detailed mutational analysis has revealed two important clusters of amino acid residues in the C terminus (C-terminal sequence 1 [CS1], aa 624 to 628; and CS2, aa 639 to 662). While both regions play a pivotal role in supporting cell viability, they make distinct contributions to ABF1 functions in various nuclear processes. CS1 specifically participates in transcriptional silencing and/or repression in a context-dependent manner, whereas CS2 is universally required for all three functions of ABF1. When tethered to specific regions of the genome, a 30-aa fragment that contains CS2 alone is sufficient for activation of transcription and chromosomal replication. In addition, CS2 is responsible for ABF1-mediated chromatin remodeling. Based on these results, we suggest that ABF1 may function as a chromatin-reorganizing factor to increase accessibility of the local chromatin structure, which in turn facilitates the action of additional factors to establish either an active or repressed chromatin state.
Mol Cell Biol 2002 Jan
PMID:Identification of a multifunctional domain in autonomously replicating sequence-binding factor 1 required for transcriptional activation, DNA replication, and gene silencing. 1175 46

In eukaryotes, transcription factors of the E2F family, in addition to having a role in cell proliferation, participate in regulating apoptosis, differentiation and development. In Arabidopsis thaliana, eight gene sequences have been identified as encoding E2F or DP homologues. DP proteins form heterodimers with E2Fs. The aim of this work was to characterize the functions of three of these factors: AtE2F-a, AtE2F-b and AtDP-a. Here we report that AtE2F-a and AtE2F-b transactivate a reporter gene via an E2F consensus cis-acting element in Arabidopsis protoplasts. AtE2F-a is a more potent activator than AtE2F-b. Furthermore, co-expression of the E2F partner AtDP-a, or the DNA binding protein AtPur alpha, modulates the activation of AtE2F-a. Taken together, these results suggest that AtE2F-a, AtE2F-b and AtDP-a share features characteristic of members of the E2F family of transcription factors. Moreover, over-expression of AtE2F-a and AtDP-a can induce differentiated, non-dividing, leaf cells to re-enter S-phase. We conclude that the transcription factor AtE2F-a plays an important role in progression into S phase, which probably correlates with its capacity to stimulate transcription.
Mol Genet Genomics 2002 Feb
PMID:AtE2F-a and AtDP-a, members of the E2F family of transcription factors, induce Arabidopsis leaf cells to re-enter S phase. 1186 94

We identified Mycobacterium tuberculosis genes preferentially expressed during infection of human macrophages using a promoter trap adapted for this pathogen. inhA encodes an enoyl-acyl carrier protein reductase that is required for mycolic acid biosynthesis (A. Quemard et al., Biochemistry 34:8235-8241, 1995) and is a major target for isoniazid (INH) in mycobacterial species (A. Banerjee et al., Science 263:227-230, 1994). Since overexpression of inhA confers INH resistance in Mycobacterium smegmatis (Banerjee et al., Science 263:227-230, 1994), we designed a promoter trap based on this gene. A library of clones, containing small fragments of M. tuberculosis DNA cloned upstream of inhA in a plasmid vector, was electroporated into M. tuberculosis, and the resulting culture was used to infect the human monocytic THP-1 cell line. Selection was made for clones surviving INH treatment during infection but retaining INH sensitivity on plates. The DNA upstream of inhA was sequenced in each clone to identify the promoter driving inhA expression. Thirteen genes identified by this method were analyzed by quantitative reverse transcription-PCR (R. Manganelli et al., Mol. Microbiol. 31:715-724, 1999), and eight of them were found to be differentially expressed from cultures grown in macrophages compared with broth-grown cultures. Several of these genes are presumed to be involved in fatty acid metabolism; one potentially codes for a unique DNA binding protein, one codes for a possible potassium channel protein, and the others code for proteins of unknown function. Genes which are induced during infection are likely to be significant for survival and growth of the pathogen; our results lend support to the view that fatty acid metabolism is essential for the virulence of M. tuberculosis.
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PMID:Mycobacterium tuberculosis genes induced during infection of human macrophages. 1201 Sep 64

MuB, an ATP-dependent DNA binding protein, is critical for selection of target sites on the host chromosome during Mu transposition. We have developed a system for observing the behavior of single MuB polymers bound to an immobilized molecule of DNA. We show that the individual polymers display a broad distribution of disassembly rates and exhibit regional variations in DNA binding. Additionally, ATP hydrolysis was obligatorily coupled to dissociation of MuB subunits from the DNA during polymer disassembly. We propose a model in which the formation of an active target complex is mediated by a conformational change within the MuB polymer that is influenced by the sequence of the DNA.
Mol Cell 2002 May
PMID:Direct observation of single MuB polymers: evidence for a DNA-dependent conformational change for generating an active target complex. 1204 43


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