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Nuclear Localization SignalsCell Nucleusalpha KaryopherinsActive Transport, Cell Nucleusbeta KaryopherinsKaryopherinsAmino Acid SequenceMolecular Sequence DataCytoplasmNuclear Export SignalsProtein Sorting SignalsNuclear ProteinsRecombinant Fusion ProteinsHeLa CellsProtein TransportGreen Fluorescent ProteinsProtein Structure, TertiaryCOS CellsCell Lineran GTP-Binding ProteinBase SequenceLuminescent ProteinsSequence DeletionSequence Homology, Amino AcidMutationProtein BindingTransfectionDNA-Binding ProteinsSubcellular FractionsCell NucleolusTranscription FactorsCercopithecus aethiopsNucleoplasminsSignal TransductionBiological TransportCell CompartmentationAmino Acid MotifsMicroscopy, FluorescenceBinding SitesMutagenesis, Site-DirectedCloning, MolecularRNA-Binding ProteinsNuclear EnvelopeNucleocytoplasmic Transport ProteinsMicroscopy, ConfocalPlasmidsAmino Acids, BasicFluorescent Antibody TechniquePhosphorylationZinc FingersViral ProteinsDNA, ComplementarySequence AlignmentRecombinant ProteinsSaccharomyces cerevisiae ProteinsSaccharomyces cerevisiaeFluorescent Antibody Technique, IndirectCarrier Proteinsbeta-GalactosidaseConserved SequenceTwo-Hybrid System TechniquesRNA, MessengerAntigens, Polyomavirus TransformingDNA PrimersBlotting, WesternReceptors, Cytoplasmic and Nuclear3T3 CellsTranscription, GeneticCells, CulturedProtein IsoformsNuclear PoreMutagenesisGenes, ReporterPhosphoproteinsTranscriptional ActivationTrans-ActivatorsNIH 3T3 CellsFatty Acids, UnsaturatedN-Acylneuraminate CytidylyltransferaseImmunohistochemistryModels, BiologicalAT-Hook MotifsNuclear Pore Complex ProteinsRepressor ProteinsFungal ProteinsNuclear MatrixCell Cycle ProteinsGene Expression RegulationTobaccoAlternative SplicingDNAImmunoprecipitationCapsid ProteinsDimerizationPlant ProteinsDrosophila ProteinsPoint MutationCell CycleGene Products, vprImmunoblotting

BRCA2AminoProteinIncreased mutationsPore complexProteinsCellularEukaryotic cellsFunctionalTransductionMembraneCellCellsStudyCenterFunctionsRoleCancerSequencesResiduesImportinNucleusSubcellularSuperfamilyBipartiteMutationsPathwaySequencePathwaysPredictionPredictNLSTransducer and activatorConsistently findAnalysesReceptorPatternsBindConfocalApproachesExamineEnvelopeFluorescenceSimilarShowIdentifyTypes

BRCA210

• BRCA2 is localised to the nucleus and the functions ascribed to it are nuclear functions. (biomedcentral.com)
• This study identifies two nuclear localisation signals (NLSs) within BRCA2 and makes the important observation that they are downstream of all known cancer-associated truncating mutations in BRCA2 . (biomedcentral.com)
• Western blots of nuclear and cytoplasmic fractions of BRCA2 mutant cells. (biomedcentral.com)
• Sequence analysis of BRCA2 revealed the presence of four potential nuclear localisation signals (NLSs), three near the C terminus. (biomedcentral.com)
• Immunofluorescence of 293T cells, transfected with plasmids expressing GFP-tagged BRCA2 fragments, suggests that the C terminus of BRCA2 is responsible for nuclear translocation. (biomedcentral.com)
• A series of plasmids encoding GFP-tagged, C-terminal fragments of BRCA2 containing mutations in the different putative NLSs were used for further immunofluorescence studies. (biomedcentral.com)
• The pancreatic cancer cell line Capan-1 only has the 6174delT mutant form of BRCA2 , which expresses a truncated BRCA2 protein, lacking both functional NLSs. (biomedcentral.com)
• If the nuclear exclusion of truncated BRCA2 proteins is also observed in primary tumour samples, then individuals with truncating mutations in BRCA2 could be screened by immunostaining. (biomedcentral.com)
• RAD51, a nuclear protein, has been shown to interact with the 6174delT form of BRCA2, which lacks the NLSs and is localised to the cytoplasm. (biomedcentral.com)
• BRCA2 nuclear localization and export sequences are listed. (frontiersin.org)

Amino2

• Most nuclear proteins contain short basic amino acid sequences known as nuclear localization signals (NLSs). (wikipedia.org)
• These experiments indicate that only two of the possible NLSs, consisting of amino acids 3263-3269 and 3381-3385, are functional. (biomedcentral.com)

Protein3

• The EBV-positive samples were subjected to amplification and sequencing of the Epstein-Barr virus nuclear protein 3A (EBNA3A) gene to evaluate the genetic diversity of EBV strains circulating in southern Chile. (bvsalud.org)
• Protein kinases are critical to cellular signalling and post-translational gene regulation, but their biological substrates are difficult to identify. (biomedcentral.com)
• Protein kinases are ubiquitous components of cellular signalling networks [ 1 ]. (biomedcentral.com)

Increased mutations1

• These are as follows: sustained proliferative signalling, cell death resistance, replicative immortality, genome instability and increased mutations, tumour-promoted inflammation, insensibility to growth repressors, deregulation of cellular energetics, evasion of immune destruction, induction of metastasis, and promotion of angiogenesis. (hindawi.com)

Pore complex2

• The transport of molecules between the nucleus and the cytoplasm in eukaryotic cells is mediated by the nuclear pore complex (NPC) which consists of 60-100 proteins and is probably 120 million daltons in molecular size. (wikipedia.org)
• Exportin 7 translocates proteins and large RNAsthrough the nuclear pore complex (NPC) and is localized to the cytoplasm and nucleus. (sdfca.org)

Proteins1

• Much has been learned regarding nuclear entry, but the cellular proteins involved are still unknown and the exact role of each viral component remains controversial [ 7 ]. (biomedcentral.com)

Cellular3

• Reactive oxygen species (ROS), generated as consequence of oxidative metabolism, activate signal transduction pathways, which contribute to cellular homeostasis [ 1 ]. (hindawi.com)
• Retroviral particles must bind specifically to their target cells, cross the plasma membrane, reverse-transcribe their RNA genome, while uncoating the cores, find their way to the nuclear membrane and penetrate into the nucleus to finally dock and integrate into the cellular genome. (biomedcentral.com)
• During the long journey from the cell surface to the nucleus, retroviruses will face multiple obstacles, since in addition to finding a path through the cytoplasm to the nucleus they have to cross two main barriers, the plasma and nuclear membranes, whilst at the same time avoiding or counteracting cellular defences that can interfere with many of these steps. (biomedcentral.com)

Eukaryotic cells2

• In eukaryotic cells the genetic material is surrounded by a membrane system called the nuclear envelope (NE). (brookes.ac.uk)
• The Nuclear Envelope is a hallmark of eukaryotic cells. (brookes.ac.uk)

Functional1

• The results highlight the importance of mid-SUNs as functional components of the ER and outer nuclear membrane. (brookes.ac.uk)

Transduction1

• Epigenetic mechanisms such as DNA methylation, histone modification, long noncoding RNA, and microRNA affect the expression of genes implicated in absorption, distribution, metabolism and excretion (ADME) of drugs, and other non-ADME genes that encode enzymes involved in the processes of cell proliferation, DNA repair, apoptosis and signal transduction key in the development of chemoresistance in cancer, specifically in platinum-based drugs. (bvsalud.org)

Membrane2

• Despite its emerging role as a key structural and signaling platform, the plant NE remains one of the least understood membrane systems. (brookes.ac.uk)
• Better understanding of this membrane system involves understanding its physical connections and its signaling and transport functions. (brookes.ac.uk)

Cell4

• But if this is not possible, oxidative stress finally activates signals that will lead to cell death. (hindawi.com)
• While much is known about biochemical signaling, many of the mechanisms that drive cell outcome in response to biophysical influences remain to be uncovered. (5dok.org)
• This signaling pathway is a highly conserved cell-to-cell communication system that regulates cell fate in development and disease. (5dok.org)
• Eph/ephrin signaling is a cell-to-cell communication pathway, which regulates cell migration and proliferation. (5dok.org)

Cells1

• We have therefore investigated the role of matrix stiffness in Notch signaling in breast cancer cells. (5dok.org)

Study1

• In this study, high-resolution confocal light microscopy is used to explore the localisation of SUN3 and SUN4 in the perinuclear region, to explore topology and to study the role of mid-SUNs on endoplasmic reticulum morphology. (brookes.ac.uk)

Center1

• and as a signaling center. (brookes.ac.uk)

Functions1

• Previous higher plant studies have associated them with functions at the nuclear envelope and the endoplasmic reticulum (ER). (brookes.ac.uk)

Role1

• This Frontiers Research Topic aims to highlight recent advances made to examine the role of the nuclear envelope (NE) as the "key border" in plants. (brookes.ac.uk)

Cancer1

• Aberrant Notch signaling in breast cancer has been found to correlate with invasion and patient outcome. (5dok.org)

Sequences7

• Most nuclear proteins contain short basic amino acid sequences known as nuclear localization signals (NLSs). (wikipedia.org)
• The enzymes include nuclear localization sequences (NLSs) and C-terminal 6-His tags. (idtdna.com)
• Cas9-RFP V3 nucleases are high purity, recombinant S. pyogenes Cas9 enzymes that are expressed as fusion proteins with nuclear localization sequences (NLSs) and C-terminal 6-His tags. (idtdna.com)
• In transient expression assay using maize protoplasts, signals of the GFP fusion products were predominantly localized in nuclei, indicating that the NLSs of OsHXK5 and OsHXK6 are functional nuclear targeting sequences in vivo. (ic4r.org)
• PSORT will then offer, based on the cNLS consensus sequences, various possible NLSs on nuclear proteins. (biomedcentral.com)
• However, many known NLSs do not match any of the consensus sequences described above. (biomedcentral.com)
• Therefore, other computational methods have been proposed to predict NLSs based on amino acid sequences. (biomedcentral.com)

Residues7

• 10. Characterization of nuclear localization signals (NLSs) and function of NLSs and phosphorylation of serine residues in subcellular and subnuclear localization of transformer-2β (Tra2β). (nih.gov)
• In contrast, deletions or mutations of a MP NLS, at residues 136-139, resulted in loss of nuclear localization. (ox.ac.uk)
• Nuclear localization signals (NLSs) are stretches of residues in proteins mediating their importing into the nucleus. (elsevierpure.com)
• In addition, residues 40 to 50 and 768 to 777 were necessary for nuclear localization of pUL47 and nuclear translocation of heterologous proteins. (biomedcentral.com)
• Nuclear localization signals (NLSs) are stretches of residues within a protein that are important for the regulated nuclear import of the protein. (biomedcentral.com)
• In this paper, we present an analysis of characterized NLSs in yeast, and find, despite the large number of nuclear import pathways, that NLSs seem to show similar patterns of amino acid residues. (biomedcentral.com)
• PSORT [ 7 ] accurately predicts protein localization by including heuristic scores based on residues frequencies, protein domains as well as motifs. (biomedcentral.com)

Importin4

• The signals for transport in the import direction, known as Nuclear Localisation Signals (NLSs), are recognised by members of the importin (Imp) superfamily of nuclear transport receptors. (pharmafocusasia.com)
• The recognition of classical NLSs on nuclear proteins is done by the importin-α subunit which in turn is recognized by the importin-β subunit. (biomedcentral.com)
• 2001). Importin- α contains an importin- β binding (IBB) domain in its N-terminus and two nuclear localization sequence (NLS)-binding sites (major and minor) in its C-terminus. (fdocument.org)
• While other importin- α isoforms recognize specific non-classical cargoes, the most conserved isoform, importin- α 1 (encoded by KPNA2 ) recognizes classical NLSs for nuclear import and is likely to be the major regulator of SAFs in mitosis (Pumroy and Cingolani, 2015). (fdocument.org)

Nucleus7

• The transport of molecules between the nucleus and the cytoplasm in eukaryotic cells is mediated by the nuclear pore complex (NPC) which consists of 60-100 proteins and is probably 120 million daltons in molecular size. (wikipedia.org)
• WT parafibromin localized to the nucleus and deletions or mutations of the three predicted BP and one of the predicted MP NLSs did not affect this localization. (ox.ac.uk)
• In addition, the OsHXK5NLS-GFP and OsHXK6NLS-GFP fusion proteins harboring nuclear localization signals were targeted predominantly in the nucleus, suggesting that these OsHXKs retain a dual-targeting ability to mitochondria and nuclei. (ic4r.org)
• However, some viral proteins, such as C, NS1, and NS5 from Zika virus (ZIKV) containing nuclear localization signals (NLSs) and nuclear export signals (NESs), are also located in the nucleus of Vero cells. (nih.gov)
• The nucleus is separated from the rest of the cell cytoplasm by a double membrane known as the Nuclear Envelope (NE), punctated by Nuclear Pore Complexes (NPCs), through which all transport between the nucleus and cytoplasm occurs. (pharmafocusasia.com)
• 45 kDa require specific targeting signals to gain either access to or egress from the nucleus. (pharmafocusasia.com)
• The pores allow the passive diffusion of small proteins, but bigger proteins entering the nucleus are usually bound by karyopherin complexes on their nuclear localization signal [ 5 ]. (biomedcentral.com)

Subcellular1

• first predicted the subcellular localization of OsHXKs using the TargetP program for determination of the presence of any N-terminal presequences, including putative mitochondrial targeting peptides (mTPs), and the predictNLS program for determination of NLSs. (ic4r.org)

Superfamily1

• The activity of the glucocorticoid receptor (GR), a nuclear receptor transcription factor belonging to subclass 3C of the steroid/thyroid hormone receptor superfamily, is typically triggered by glucocorticoid hormones. (nih.gov)

Bipartite2

• In addition, the TUSP proteins contain a tubby signature motif (FXGRVTQ), two bipartite nuclear localization signals (NLSs) at the C-terminal, two proline-rich regions, one WD40 repeat region and one suppressor of cytokines signaling domain. (elsevierpure.com)
• We also explored using specific models for the monopartite and bipartite NLSs, but surprisingly, found no significant improvement in positive predictive value. (biomedcentral.com)

Mutations1

• Mutations that result in excess Wnt signaling are associated with a number of human cancers especially colorectal cancer ( Polakis, 2007 ). (silverchair.com)

Pathway1

• We use Drosophila as a model system for studying Wnt signaling, because its powerful genetics allows the discovery of new pathway components. (silverchair.com)

Sequence1

• The performance comparison between SeqNLS with and without the linear motif scoring shows that linear motif features are highly complementary to sequence features in discerning NLSs. (elsevierpure.com)

Pathways2

• Although patience is a virtue when it comes to deciphering the many mechanisms GR uses to influence various signaling pathways, the current review is testimony of the fact that groundbreaking mechanistic work has been accumulating over the past years and steadily continues to grow. (nih.gov)
• Although there are many nuclear import pathways in eukaryotic cells, most of these have not been characterized in detail. (biomedcentral.com)

Prediction3

• SeqNLS: nuclear localization signal prediction based on frequent pattern mining and linear motif scoring. (elsevierpure.com)
• For the two independent datasets, our SeqNLS not only can consistently find over 50% of NLSs with prediction precision of at least 0.7, but also outperforms other state-of-the-art NLS prediction methods in terms of F1 score or prediction precision with similar or higher recall rates. (elsevierpure.com)
• Dive into the research topics of 'SeqNLS: nuclear localization signal prediction based on frequent pattern mining and linear motif scoring. (elsevierpure.com)

PredictNLS1

• We compiled a list of experimentally verified NLSs in yeast and found that PredictNLS [ 8 ] predicts 10% of the NLSs in this set. (biomedcentral.com)

Transducer and activator1

• Moreover, pUL47 significantly inhibited polyriboinosinic:polyribocytidylic acid [poly(I:C)]-induced interferon beta (IFN-β) production and downregulated interferon-stimulated gene (ISG) expression, such as Mx and oligoadenylate synthetase-like (OASL), by interacting with signal transducer and activator of transcription-1 (STAT1). (biomedcentral.com)

Consistently find1

• We show that our method is able to consistently find 37% of the NLSs with a low false positive rate and that our method retains its true positive rate outside of the yeast data set used for the training parameters. (biomedcentral.com)

Analyses1

• Western blot analyses of nuclear and cytoplasmic fractions from the transfected cells were also performed. (ox.ac.uk)

Receptor1

• Two of the latter affect the HAT domain, while one maps within the conserved nuclear receptor binding of (aa 1-170) and will probably destroy a Nuclear Localization Signal. (nih.gov)

Patterns2

• NLSs are known to have diverse patterns, of which only a limited number are covered by currently known NLS motifs. (elsevierpure.com)
• Here we propose a sequential pattern mining algorithm SeqNLS to effectively identify potential NLS patterns without being constrained by the limitation of current knowledge of NLSs. (elsevierpure.com)

Bind1

• Unlike other PY-NLSs, which generally bind Kapβ2 in fully extended conformations, the FUS peptide is atypical as its central portion forms a 2.5-turn α-helix. (nih.gov)

Confocal1

• In this study, high-resolution confocal light microscopy is used to explore the localisation of SUN3 and SUN4 in the perinuclear region, to explore topology and to study the role of mid-SUNs on endoplasmic reticulum morphology. (brookes.ac.uk)

Approaches1

• In combination with other agents, tumour cell-specific nuclear targeting approaches have great potential in developing truly tumour cell-specific therapeutic treatments. (pharmafocusasia.com)

Examine2

• This Frontiers Research Topic aims to highlight recent advances made to examine the role of the nuclear envelope (NE) as the "key border" in plants. (brookes.ac.uk)
• To further examine function of the predicted NLSs, The NLSs of OsHXK5 and OsHXK6 to GFP were fused, respectively, thereby generating OsHXK5NLS-GFP and OsHXK6NLS-GFP. (ic4r.org)

Envelope2

• My research focuses on the nuclear envelope in plants. (brookes.ac.uk)
• Previous higher plant studies have associated them with functions at the nuclear envelope and the endoplasmic reticulum (ER). (brookes.ac.uk)

Fluorescence1

• The quantitative analysis of GFP fluorescence intensity supported that GFP signals were mostly present in nuclei of maize protoplasts expressing OsHXK5DmTP-GFP or OsHXK6DmTP-GFP. (ic4r.org)

Similar1

• The FUS PY-NLS occupies the structurally invariant C-terminal arch of Kapβ2, tracing a path similar to that of other characterized PY-NLSs. (nih.gov)

Show1

• The experiment results on the newly curated Yeast and Hybrid datasets show that SeqNLS is effective in detecting potential NLSs. (elsevierpure.com)

Identify2

• Epistasis experiments from many laboratories have used these phenotypes to identify genes required for proper Wg signaling. (silverchair.com)
• In order to test the predictive power of computational methods to predict NLSs in S. cerevisiae , we sought to identify a set of experimentally confirmed NLSs. (biomedcentral.com)

Types1

• Wnt signaling generates embryonic pattern in many tissue types from epidermal epithelia to the nervous system. (silverchair.com)