Search results for "nuclear localization"
showing 10 items of 30 documents
Convergence of the target of rapamycin and the Snf1 protein kinase pathways in the regulation of the subcellular localization of Msn2, a transcriptio…
2002
The subcellular localization of Msn2, a transcriptional activator of STRE (stress response element)-regulated genes, is modulated by carbon source availability. In cells growing in glucose, Msn2 is located mainly in the cytosol, whereas in carbon source-starved cells, Msn2 is located largely inside the nucleus. However, in cells lacking Reg1 (the regulatory subunit of the Reg1/Glc7 protein phosphatase complex), the regulation of subcellular distribution is absent, Msn2 being constitutively present in the cytosol. The localization defect in these mutants is specific for carbon starvation stress, and it is because of the presence of an abnormally active Snf1 protein kinase that inhibits the n…
Characterization of aging-associated up-regulation of constitutive nuclear factor-kappa B binding activity.
2001
Changes occur in gene expression during aging in vivo and in replicative senescence in vitro, suggesting that aging can affect gene regulation. We have recently observed age-related changes in ubiquitously expressed, oxidative stress-responsive nuclear factor-kappa B (NF-kappa B) pathway during aging. Here we report a significant age-related increase in nuclear NF-kappa B binding activity together with increased protein levels of p52 and p65 components in rat liver. An additional, higher molecular weight protein band seen in their western blots suggests that their post-translational modification (but not phosphorylation) occurs in liver, which might affect their nuclear localization and bin…
Attenuation of NF-κB Signaling Response to UVB Light during Cellular Senescence
1999
The ability of cells to adapt to environmental stresses undergoes a progressive reduction during aging. NF-kappaB-mediated signaling is a major defensive system against various environmental challenges. The aim of this study was to find out whether replicative senescence affects the response of the NF-kappaB signaling pathway to UVB light in human WI-38 and IMR-90 fibroblasts. The exposure of early passage fibroblasts to UVB light inhibited the proliferation and induced a flat phenotype similar to that observed in replicatively senescent fibroblasts not exposed to UVB light. The UVB radiation dose used (153 mJ/cm2) did not induce apoptosis in either early or late passage WI-38 fibroblasts. …
Transcriptional Activity and Nuclear Localization of Cabut, the Drosophila Ortholog of Vertebrate TGF-β-Inducible Early-Response Gene (TIEG) Proteins
2011
Background Cabut (Cbt) is a C2H2-class zinc finger transcription factor involved in embryonic dorsal closure, epithelial regeneration and other developmental processes in Drosophila melanogaster. Cbt orthologs have been identified in other Drosophila species and insects as well as in vertebrates. Indeed, Cbt is the Drosophila ortholog of the group of vertebrate proteins encoded by the TGF-s-inducible early-response genes (TIEGs), which belong to Sp1-like/Kruppel-like family of transcription factors. Several functional domains involved in transcriptional control and subcellular localization have been identified in the vertebrate TIEGs. However, little is known of whether these domains and fu…
Yeast karyopherin Kap95 is required for cell cycle progression at Start
2010
Abstract Background The control of the subcellular localization of cell cycle regulators has emerged as a crucial mechanism in cell division regulation. The active transport of proteins between the nucleus and the cytoplasm is mediated by the transport receptors of the β-karyopherin family. In this work we characterized the terminal phenotype of a mutant strain in β-karyopherin Kap95, a component of the classical nuclear import pathway. Results When KAP95 was inactivated, most cells arrested at the G2/M phase of the cell cycle, which is in agreement with the results observed in mutants in the other components of this pathway. However, a number of cells accumulate at G1, suggesting a novel r…
A Deletion of the Nuclear Localization Signal Domain in the Fus Protein Induces Stable Post-stress Cytoplasmic Inclusions in SH-SY5Y Cells
2021
Mutations in Fused-in-Sarcoma (FUS) gene involving the nuclear localization signal (NLS) domain lead to juvenile-onset Amyotrophic Lateral Sclerosis (ALS). The mutant protein mislocalizes to the cytoplasm, incorporating it into Stress Granules (SG). Whether SGs are the first step to the formation of stable FUS-containing aggregates is still unclear. In this work, we used acute and chronic stress paradigms to study the SG dynamics in a human SH-SY5Y neuroblastoma cell line carrying a deletion of the NLS domain of the FUS protein (homozygous: ΔNLS–/–; heterozygous: ΔNLS+/–). Wild-type (WT) cells served as controls. We evaluated the subcellular localization of the mutant protein through immuno…
RNA-controlled nucleocytoplasmic shuttling of mRNA decay factors regulates mRNA synthesis and initiates a novel mRNA decay pathway
2021
AbstractmRNA level is controlled by factors that mediate both mRNA synthesis and decay, including the exonuclease Xrn1 - a major mRNA synthesis and decay factor. Here we show that nucleocytoplasmic shuttling of Xrn1 and of some of its associated mRNA decay factors plays a key role in determining both mRNA synthesis and decay. Shuttling is regulated by RNA-controlled binding of the karyopherin Kap120 to two nuclear localization sequences (NLSs) in Xrn1. The decaying RNA binds and masks NLS1, establishing a link between mRNA decay and Xrn1 shuttling. Mutations in the two NLSs, which prevent Xrn1 import, compromise transcription and, unexpectedly, also the cytoplasmic decay of ∼50% of the cell…
Asialofetuin Liposomes for Receptor-Mediated Gene Transfer into Hepatic Cells
2003
Publisher Summary The liver is an excellent organ for gene transfer in treating a wide variety of diseases that affect liver function. It is an ideal organ for a high amount of expression of therapeutic genes and efficient systemic distribution of the resulting therapeutic proteins secreted into the bloodstream. For strategies of liver-destined gene therapy, the liver sinusoid endothelium contains pores with a mean diameter of 100 nm, which allow small vectors to leave the blood circulation and reach the hepatocytes. The preparation of asialofetuin–liposomes targeted to hepatocytes can be made by covalent coupling of asialofetuin glycoprotein (ASF) onto the liposome surface, by the use of h…
The effect of nanoparticle size and NLS density on nuclear targeting in cancer and normal cells; impaired nuclear import and aberrant nanoparticle in…
2017
The cell nucleus is an interesting target in many diseases with particular interest in cancer. Previously, nuclear targeted small and large chitosan nanoparticles (S-NPs≈25nm, and L-NPs≈150nm respectively), modified with low, intermediate and high densities of NLS (L-NLS, I-NLS and H-NLS) were developed and assessed in L929 fibroblasts. However, to evade apoptosis and stimulate tumor growth cancer cells are capable of manipulating the nuclear-cytoplasmic transport on many levels, making NPs that are capable of nuclear targeting in normal cells incapable of doing so in cancer. For such reason, here, the nuclear delivery efficiency of S-NPs and L-NPs was assessed as a function of their NLS de…
Nuclear localization but not PML protein is required for incorporation of the papillomavirus minor capsid protein L2 into virus-like particles.
2004
ABSTRACT Recent reports suggest that nuclear domain(s) 10 (ND10) is the site of papillomavirus morphogenesis. The viral genome replicates in or close to ND10. In addition, the minor capsid protein, L2, accumulates in these subnuclear structures and recruits the major capsid protein, L1. We have now used cell lines deficient for promyelocytic leukemia (PML) protein, the main structural component of ND10, to study the role of this nuclear protein for L2 incorporation into virus-like particles (VLPs). L2 expressed in PML protein knockout (PML −/− ) cells accumulated in nuclear dots, which resemble L2 aggregates forming at ND10 in PML protein-containing cells. These L2 assemblies also attracted…