Search results for "Gene expression"
showing 10 items of 4085 documents
The differentiation antigen NY-BR-1 is a potential target for antibody-based therapies in breast cancer
2007
Antibody-based cancer immunotherapy relies on the identification and characterization of target antigens and the development of potent antibodies recognizing the target. Here we report the expression analysis and molecular characterization of the differentiation antigen NY-BR-1, which we previously identified by using the SEREX (serological analysis of recombinant cDNA expression libraries) method. Corroborating methodologies, including mRNA quantitation and immunoblotting show that NY-BR-1 is strongly expressed in >70% of 129 breast tumors. Application of a NY-BR-1 specific antibody demonstrated NY-BR-1 expression in primary and metastastic breast cancers. In contrast, most of the breast c…
Glutathione is recruited into the nucleus in early phases of cell proliferation.
2007
We have studied the possible correlation between nuclear glutathione distribution and the progression of the cell cycle. The former was studied by confocal microscopy using 5-chloromethyl fluorescein diacetate and the latter by flow cytometry and protein expression of Id2 and p107. In proliferating cells, when 41% of them were in the S+G(2)/M phase of the cell cycle GSH was located mainly in the nucleus. When cells reached confluence (G(0)/G(1)) GSH was localized in the cytoplasm with a perinuclear distribution. The nucleus/cytoplasm fluorescence ratio for GSH reached a maximal mean value of 4.2 +/- 0.8 at 6 h after cell plating. A ratio higher than 2 was maintained during exponential cell …
Nuclear Translocation of Mismatch Repair Proteins MSH2 and MSH6 as a Response of Cells to Alkylating Agents
2000
Mammalian mismatch repair has been implicated in mismatch correction, the prevention of mutagenesis and cancer, and the induction of genotoxicity and apoptosis. Here, we show that treatment of cells specifically with agents inducing O(6)-methylguanine in DNA, such as N-methyl-N'-nitro-N-nitrosoguanidine and N-methyl-N-nitrosourea, elevates the level of MSH2 and MSH6 and increases GT mismatch binding activity in the nucleus. This inducible response occurs immediately after alkylation, is long-lasting and dose-dependent, and results from translocation of the preformed MutSalpha complex (composed of MSH2 and MSH6) from the cytoplasm into the nucleus. It is not caused by an increase in MSH2 gen…
Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins.
2001
The L1 adhesion molecule plays an important role in axon guidance and cell migration in the nervous system. L1 is also expressed by many human carcinomas. In addition to cell surface expression, the L1 ectodomain can be released by a metalloproteinase, but the biological function of this process is unknown. Here we demonstrate that membrane-proximal cleavage of L1 can be detected in tumors and in the developing mouse brain. The shedding of L1 involved a disintegrin and metalloproteinase (ADAM)10, as transfection with dominant-negative ADAM10 completely abolishes L1 release. L1-transfected CHO cells (L1-CHO) showed enhanced haptotactic migration on fibronectin and laminin, which was blocked …
Multifunctionality of F-rich nucleoporins
2020
Nucleoporins (Nups) represent a range of proteins most known for composing the macromolecular assembly of the nuclear pore complex (NPC). Among them, the family of intrinsically disordered proteins (IDPs) phenylalanine-glycine (FG) rich Nups, form the permeability barrier and coordinate the high-speed nucleocytoplasmic transport in a selective way. Those FG-Nups have been demonstrated to participate in various biological processes besides nucleocytoplasmic transport. The high number of accessible hydrophobic motifs of FG-Nups potentially gives rise to this multifunctionality, enabling them to form unique microenvironments. In this review, we discuss the multifunctionality of disordered and …
Analysis of cytochrome C oxidase subunits III and IV expression in developing rat brain
2004
Abstract Cytochrome c oxidase (COX) complex is built up with both nucleus- and mitochondrion-encoded subunits. Biogenesis and assembly of the complex thus requires fine cross-talk between the two compartments. In order to shed light on the regulation of nuclear–mitochondrial interactions, we studied the expression of COXIII (mitochondrion-encoded) and COXIV (nucleus-encoded) in adult rat tissues and rat developing brain. We found that the levels of COXIV protein and mRNA are not linearly related, thus suggesting a post-transcriptional mode of regulation. In agreement with this observation, we report the presence of a protein that specifically binds to the 3′-untranslated region of COXIV mRN…
Cytoglobin is a respiratory protein in connective tissue and neurons, which is up-regulated by hypoxia.
2004
Cytoglobin is a recently discovered vertebrate globin distantly related to myoglobin, and its function is unknown. Here we present the first detailed analysis of the distribution and expression of cytoglobin. Northern and Western blotting experiments show the presence of cytoglobin mRNA and protein in a broad range of tissues. Quantitative PCR demonstrates an up-regulation of cytoglobin mRNA levels in rat heart and liver under hypoxic conditions (22 and 44 h of 9% oxygen). Immunofluorescence studies with three antibodies directed against different epitopes of the protein consistently show cytoglobin in connective tissue fibroblasts as well as in hepatic stellate cells. Cytoglobin is also pr…
Regulation of ribonucleotide reductase in response to iron deficiency
2011
Ribonucleotide reductase (RNR) is an essential enzyme required for DNA synthesis and repair. Although iron is necessary for class Ia RNR activity, little is known about the mechanisms that control RNR in response to iron deficiency. In this work, we demonstrate that yeast cells control RNR function during iron deficiency by redistributing the Rnr2–Rnr4 small subunit from the nucleus to the cytoplasm. Our data support a Mec1/Rad53-independent mechanism in which the iron-regulated Cth1/Cth2 mRNA-binding proteins specifically interact with the WTM1 mRNA in response to iron scarcity, and promote its degradation. The resulting decrease in the nuclear-anchoring Wtm1 protein levels leads to the re…
The Yeast RNA Polymerase II-associated Factor Iwr1p Is Involved in the Basal and Regulated Transcription of Specific Genes
2009
RNA polymerase II (RNA pol II) is a multisubunit enzyme that requires many auxiliary factors for its activity. Over the years, these factors have been identified using both biochemical and genetic approaches. Recently, the systematic characterization of protein complexes by tandem affinity purification and mass spectroscopy has allowed the identification of new components of well established complexes, including the RNA pol II holoenzyme. Using this approach, a novel and highly conserved factor, Iwr1p, that physically interacts with most of the RNA pol II subunits has been described in yeast. Here we show that Iwr1p genetically interacts with components of the basal transcription machinery …
Molecular basis of the functional distinction between Cln1 and Cln2 cyclins
2012
Cln1 and Cln2 are very similar but not identical cyclins. In this work, we tried to describe the molecular basis of the functional distinction between Cln1 and Cln2. We constructed chimeric cyclins containing different fragments of Cln1 and Cln2 and performed several functional analysis that make it possible to distinguish between Cln1 or Cln2. We identified that region between amino acids 225 and 299 of Cln2 is not only necessary but also sufficient to confer Cln2 specific functionality compared with Cln1. We also studied Cln1 and Cln2 subcellular localization identifying additional differences between them. Both cyclins are distributed between the nucleus and the cytoplasm, but Cln1 shows…