These findings provide the initial indication of a novel cell density-dependent pathway that is responsible for the regulation of VHL cellular localization. (nih.gov)
IκBζ, an atypical member of the nuclear IκB family of proteins, is expressed at low levels in most resting cells, but is induced upon stimulation of Toll-like/IL-1 receptors through an IRAK1/IRAK4/NFκB-dependent pathway. (oncotarget.com)
These receptors function as ligand-dependent transcription factors [2] - [4] , acting either through the transcriptional regulation of genes (genomic pathway) or through membrane and cytoplasmic signaling cascades (non-genomic pathway). (scirp.org)
Current BC treatment options exclusively target the genomic signaling pathway. (scirp.org)
Downregulation of Herg1 suppresses osteosarcoma proliferation and invasion by targeting Hippo signaling pathway]. (cancerindex.org)
RNA-seq results indicated that CSE1L activated the MAPK signaling pathway in NSCLC cells by increasing activity of P65. (researchsquare.com)
CSE1L promotes proliferation of NSCLC cells by activating the MAPK signaling pathway and inhibiting apoptosis in coordination with P65. (researchsquare.com)
Skeletal muscle and myogenic C2C12 cells were used to study the effects of MSY3 phosphorylation in vivo and in vitro on its sub-cellular localization and activity, by blocking the IGF1/PI3K/Akt pathway, by Akt depletion and over-expression, and by mutating potential MSY3 phosphorylation sites. (biomedcentral.com)
This study highlights a previously undescribed Akt-mediated signaling pathway involved in the repression of myogenin expression in myogenic cells and in mature muscle. (biomedcentral.com)
Pathways6
USP4 has substrates of important function in a number of cell signalling pathways, including the NF-κB, TGF-β, Wnt/β-catenin, p53, and spliceosome pathways. (wikipedia.org)
Estrogen signaling pathways have been identified as efficient targets of breast cancer therapy, given their key role in promoting breast tumor growth. (scirp.org)
Estrogens stimulate the proliferation and the differentiation of breast epithelial cells through the activation of downstream mitogenic signaling pathways, namely via the estrogen receptors ERα and ERβ. (scirp.org)
Therefore, the identification of new actors of estrogen signaling pathways should improve treatment specificity and thus overcome cancer drug resistance. (scirp.org)
These therapeutic molecules serve as important sources for new drugs that interfere with cellular proliferation, apoptosis, metastasis, and angiogenesis by regulating signaling pathways. (biomedcentral.com)
Moreover, many canonical cancer-associated signaling pathways induce metabolic reprogramming. (pharmaceuticalintelligence.com)
Nucleo-cytoplasmic transport4
The thesis entitled „Investigations on the significance of nucleo-cytoplasmic transport for the biological function of cellular proteins" aimed to unreveal molecular mechanisms in order to improve our understanding of the impact of nucleo-cytoplasmic transport on cellular functions. (uni-frankfurt.de)
Within the scope of this work, it could be shown that regulated nucleo-cytoplasmic transport of a subfamily of homeobox transcription factors controlled their intra- and intercellular transport, and thereby influencing also their transcriptional activity. (uni-frankfurt.de)
The impact of nucleo-cytoplasmic transport on the regulation of apoptosis was underlined by showing that the evolutionary conservation of a NES within the anti-apoptotic protein survivin plays an essential role for its dual function in the inhibition of apoptosis and ordered cell division. (uni-frankfurt.de)
In summary, this work does not only underline the general significance of nucleo-cytoplasmic transport for cell biology, but also demonstrates its potential for the development of novel therapies against diseases like cancer and viral infections. (uni-frankfurt.de)
Nucleus7
Those signals initiate the translocation of USP4 to the nucleus from the cytoplasm and vice versa, respectively. (wikipedia.org)
Western blot analysis of nuclear and cytoplasmic fractions identified Bok in both the nucleus and the cytoplasm of HEK 293T cells, HeLa cells, and breast cancer cells, and its nuclear concentration increased after treatment of those cells with leptomycin B, an inhibitor of the exportin Crm1. (deathbase.org)
Transport receptors constantly shuttle between the nucleus and cytoplasm, thereby rapidly crossing the permeability barrier of nuclear pores (59). (irjs.info)
Proteins bearing a classical nuclear localization signal (cNLS) are imported into the nucleus by the importin / heterodimer (26, 49, 55). (irjs.info)
Export and import of mRNA and specific proteins from the nucleus is a key step in intracellular signaling and can lead to cell proliferation or apoptosis. (researchsquare.com)
Western blot analysis of HD brain tissue shows full-length huntingtin protein in the nuclear fraction as well as abundant immunopositive bands at lower molecular weight, suggesting proteolytic products in the nucleus. (jci.org)
Proteins4
Besides cis-active transport Signals, also post-translational modifications can influence the localization and biological activity of proteins in trans. (uni-frankfurt.de)
Apicomplexan parasites such as and export element (PEXEL) directs proteins into erythrocytes to remodel the host cell and establish infection. (colinsbraincancer.com)
GRA15 is sufficient for host nuclear factor kappa B activation (10) and GRA1 GRA4 and GRA7 are effective antigens used in DNA vaccines (11 12 These findings demonstrate that secretory proteins play a significant role in host cell modulation and immune responses. (colinsbraincancer.com)
The control of nuclear localization via phosphorylation and dephosphorylation serves as the primary regulatory mechanism for MiT family proteins, and several kinases and phosphatases have been identified to directly determine the transcriptional activities of MiT proteins. (molcells.org)
Protein12
USP4 is a nucleocytoplasmic shuttling protein that bears a functional nuclear localization signal (NLS) 766QPQKKKK772 and a nuclear export signal (NES) 133VEVYLLELKL142. (wikipedia.org)
The proportion of cytoplasmic to nuclear USP4 pool varies depending on the cell type, the phase of cell cycle and the level of protein expression. (wikipedia.org)
Selinexor, a small molecule that inhibits nuclear export protein XPO1, has demonstrated efficacy in solid tumors and hematologic malignancies with the evidence of clinical activity in sarcoma as a single agent. (aacrjournals.org)
A putative nuclear localization signal, a nuclear export signal, and a cytoplasmic retention locus have been identified in the VHL protein. (nih.gov)
Des weiteren konnte gezeigt werden, daß die evolutionäre Konservierung eines nuklearen Exportsignals (NES) im anti-apoptotischen Protein Survivin für dessen duale Funktion, der Verhinderung von Apoptose und der geordneten Zellteilung, eine essentielle Rolle spielt. (uni-frankfurt.de)
TDP-43 is a 43 kDa heterogeneous nuclear ribonuclear protein (hnRNP) composed of 414 amino acids and is encoded by the TARDBP gene located on chromosome 1 (1p36.22) [ 14 ]. (biomedcentral.com)
These data highlight that ESE-1 contains NLS and NES signals that play a critical role in regulating its subcellular localization and function, and that an intact SAR domain mediates MEC transformation exclusively in the cytoplasm, via a novel nontranscriptional mechanism, whereby the SAR motif is accessible for ligand and/or protein interactions. (biomedcentral.com)
The HT/PEXEL motif serves as a cleavage signal and may contributes to protein-protein associations. (colinsbraincancer.com)
shMTHFR enhanced cytosolic and nuclear SHMT/DHFR/TYMS protein complex, MTHFD1 ( A ), as well as DNA repair protein MLH1, and p53 expressions ( B ) in folate repletion and folate depletion. (bioz.com)
shMTHFR enhanced cytosolic and nuclear SHMT/DHFR/TYMS 1 protein expression 2 in HepG2 cells. (bioz.com)
Lower MTHFR is associated with increased proportional cell populations in the G2/M phase, increased cytosol, and nuclear SHMT1/DHFR/TYMS protein expression under folate deficiency. (bioz.com)
ZO-1 is a protein located on a cytoplasmic membrane surface of intercellular tight junctions. (thermofisher.com)
Cytosol1
The accumulation of FOXO1 in the cytosol and nuclear exclusion promoted cell proliferation and inhibited apoptosis. (biomedcentral.com)
Epithelial1
Here, we report that treatment with orally administered ginger-derived nanoparticles (GDNP) prevents insulin resistance by restoring homeostasis in gut epithelial Foxa2 mediated signaling in mice fed a high-fat diet (HFD). (thno.org)
Apoptosis3
NF-κB ( Nuclear Factor kappa B ) is a ubiquitous family of transcription factors involved in biological processes such as inflammation, immunity, proliferation and apoptosis [ 1 - 3 ]. (oncotarget.com)
Nuclear translocation of the pro-apoptotic Bcl-2 family member Bok induces apoptosis. (deathbase.org)
Advantages (C-E). The altered metabolism of cancer cells is likely to imbue them with several proliferative and survival advantages, such as enabling cancer cells to execute the biosynthesis of macromolecules (C), to avoid apoptosis (D), and to engage in local metabolite-based paracrine and autocrine signaling (E). Potential Liabilities (F and G). This altered metabolism, however, may also confer several vulnerabilities on cancer cells. (pharmaceuticalintelligence.com)
Apoptotic2
Mutating the nuclear export signal of Bok by site-directed mutagenesis resulted in an increase in its nuclear localization and apoptotic activity. (deathbase.org)
These results suggest that nuclear export of Bok is a regulated process mediated by Crm1, and constitutes the first report of a link between the apoptotic activity and nuclear localization of a pro-apoptotic member of the Bcl-2 family. (deathbase.org)
Pore1
The website of exchange may be the nuclear pore complicated (NPC), among the largest macromolecular assemblies inside a eukaryotic cell, which may be traversed inside a unaggressive or a facilitated way. (irjs.info)
Importins2
The largest class of nuclear transport receptors is the superfamily of importin -like factors (also named karyopherins) that PCI-32765 distributor can be classified as importins (import karyopherin) and exportins (export karyopherin) depending on the direction in which they transport the cargo (reviewed PCI-32765 distributor in references 25, 32, 43, 72, and 80). (irjs.info)
Cargo binding and release of importins and exportins is controlled by a steep RanGTP gradient, which is maintained across the nuclear envelope through the asymmetric distribution of factors that regulate the guanine nucleotide-bound state of Ran (25, 41, PCI-32765 distributor 43, 47, 76). (irjs.info)
Regulation1
In order to further dissect the regulation of nuclear transport and to efficiently identify transport inhibitors, cell-based assays are urgently required. (uni-frankfurt.de)
Putative1
To map the minimal functional nuclear localization (NLS) and nuclear export (NES) signals, we fused in-frame putative NLS and NES motifs between GFP and the SAR domain. (biomedcentral.com)
Cancer5
Thus, this novel mechanism by which selinexor suppresses NFκB signaling provides unique opportunities for cancer therapy, especially when this drug is combined with a proteasome inhibitor. (aacrjournals.org)
Since survivin is considered a bona fide cancer therapy target, these results strongly encourage future work to identify molecular decoys that specifically inhibit the nuclear export of survivin as novel therapeutics. (uni-frankfurt.de)
Lnc408-CBY1-β-catenin signaling axis might serve as a new diagnostic and therapeutic target for breast cancer. (nature.com)
ESE-1 initiates transformation of MCF-12A cells via a non-transcriptional, cytoplasmic process that is mediated by a unique 40-amino acid serine and aspartic acid rich (SAR) subdomain, whereas, ESE-1's nuclear transcriptional property is required to maintain the transformed phenotype of MCF7, ZR-75-1 and T47D breast cancer cells. (biomedcentral.com)
Drivers (A and B). The metabolic derangements in cancer cells may arise either from the selection of cells that have adapted to the tumor microenvironment or from aberrant signaling due to oncogene activation. (pharmaceuticalintelligence.com)
Cellular1
Therefore, the cellular assay Systems developed in this work may not only serve to identify synthetic nuclear export and Import inhibitors but may also be applied in systematic RNAi-screening approaches to identify novel components of the transport machinery. (uni-frankfurt.de)
Receptor2
Many nuclear transport procedures are mediated by soluble transportation receptors that understand particular sequences or structural characteristics of their cargoes and facilitate the passage of receptor-cargo complexes through the NPC. (irjs.info)
Data expand the understanding of the mechanism by which the NR4A2 nuclear receptor can facilitate DNA DSB repair. (cusabio.com)
Stress responses1
Cytoplasmic stress responses in Er1 F/− macrophages. (nature.com)
Insulin1
Genes associated with metabolism or insulin signaling were further quantified using the real time polymerase chain reaction (RT-PCR). (thno.org)
Kappa3
A luciferase reporter assay was used to examine the transcriptional activity of nuclear factor kappa - light - chain - enhancer of activated B cells (NF-κB). (biomedcentral.com)
We previously showed that genotoxic stress induced an active extracellular release of nucleophosmin (NPM) in human cardiac mesenchymal progenitor cells, and that serum deprivation provokes NPM secretion from human endothelial cells, eliciting inflammation via nuclear factor kappa B (NF-kB) transcriptional activation. (frontiersin.org)
It also regulates the stability and activity of transcription factors including p53 and nuclear factor kappa B (NF-κB) ( 5 , 6 ). (frontiersin.org)
Motifs1
Additional signals for microneme targeting include two tyrosine-based motifs SYHYY and EIEYE at the C-terminus of MIC2 (16). (colinsbraincancer.com)
Transcriptional1
While previous publications have established ESE-1's transcription factor function, we have reported that ESE-1 initiates transformation of MECs via a novel non-nuclear, non-transcriptional mechanism [ 13 ]. (biomedcentral.com)
Processes1
Maps also chart the connectivity between these molecules, elucidating the circuits and signaling processes that give rise to function. (stanford.edu)
Nucleocytoplasmic1
Nucleocytoplasmic localization of FOXO1 was determined by nucleocytoplasmic isolation and immunofluorescence. (biomedcentral.com)
In these transport cycles GTP hydrolysis constitutes the sole input of metabolic energy, which allows import and export cargoes to accumulate against gradients of chemical activities (21, 29, 38, 60, 67, 78). (irjs.info)
Initiate2
Furthermore, we show that exclusive cytoplasmic targeting of the SAR domain is sufficient to initiate transformation, and we report that an intact SAR domain is required, since block mutagenesis reveals that an intact SAR domain is necessary to maintain its full transforming potency. (biomedcentral.com)
We've shown a 40-amino acidity (AA) serine and aspartic acidity rich (SAR) site inside the ESE-1 can be both required and adequate to mediate ESE-1 changing function which enforced nuclear localization of full-length ESE-1 or from the SAR site only abrogates ESE-1 capability to initiate change [13]. (ap26113.com)
Sequence2
We showed here that human Bok is the only member of the Bcl-2 family to have a leucine-rich sequence indicative of a nuclear export signal within its BH3 domain. (deathbase.org)
A signal sequence domain essential for processing, but not import, of mitochondrial pre-ornithine carbamyl transferase. (mcmaster.ca)
Expression1
shMTHFR promoted nuclear MLH1/p53 expression under folate deficiency that can protect cells from folate depletion induced micronuclei and uracil misincorporation. (bioz.com)
Single1
Selinexor induced IκB nuclear localization as a single agent, and the effect was enhanced by stabilization of IκB when pretreated with the proteasome inhibitor carfilzomib. (aacrjournals.org)
Process1
This process is dependent on the nuclear export signal (NES) of GTSE1 (Monte et al. (reactome.org)