Targets protein eukaryotic initiation factor 2. Medical search. Frequent questions

MAP kinase-interacting serine/threonine-protein kinase 2 is an enzyme that in humans is encoded by the MKNK2 gene. (wikipedia.org)
The gamma(1)34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1alpha to dephosphorylate the alpha subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase. (scienceopen.com)
In human cells infected with herpes simplex virus 1 the double-stranded RNA-dependent protein kinase (PKR) is activated but phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2) and total shutoff of protein synthesis is observed only in cells infected with gamma(1)z34.5- mutants. (scienceopen.com)
Extracellular signal-regulated kinase (ERK) is a part of the mitogen-activated protein kinase (MAPK) signaling pathway which allows the transduction of various cellular signals to final effectors and regulation of elementary cellular processes. (mdpi.com)
The protein levels of phospho-phosphatidylinositol 3-kinase, protein kinase B, phospho-eukaryotic initiation factor 4E binding protein-1 (p-4E-BP1), 4E-BP1 and ribosomal protein S6 kinase 1, in the liver of fish fed the 0.84% diet were higher than those in fish fed the 0.40% diet. (researchsquare.com)
Phosphatidylinositol-3-kinase (PI3-K) pathway has been reported as an important intracellular mediator frequently activated in cancer cells [ 2 ]. (biomedcentral.com)
The General Control Nonderepressible 2 (GCN2) kinase is a conserved member of the integrated stress response (ISR) pathway that represses protein translation and helps cells to adapt to conditions of nutrient shortage. (biomedcentral.com)
VCP inhibitors also perturbed intracellular amino acid levels, activated eukaryotic translation initiation factor 2α kinase 4 (EIF2AK4), and enhanced cellular dependence on amino acid supplies, consistent with a failure of amino acid homeostasis. (ox.ac.uk)
IRE1 (ERN1) is a protein kinase and endoribonuclease that facilitates cytosolic splicing of (XBP1s) mRNA, thereby Benzylpenicillin potassium enhancing expression of the XBP1s isoform, which induces transcription of genes involved in Benzylpenicillin potassium ER-associated protein degradation (ERAD), lipid synthesis, and protein folding (7, 8). (iwap2018.com)
Structural analysis identifies imidazo[1,2-b]pyridazines as PIM kinase inhibitors with in vitro antileukemic activity. (ox.ac.uk)
The high-resolution crystal structure of a PIM1 inhibitor complex revealed that imidazo[1,2-b]pyridazines surprisingly interact with the NH(2)-terminal lobe helix alphaC rather than with the kinase hinge region. (ox.ac.uk)
In vitro kinase assays and immunoblotting using lysates from human MV4;11 leukemic cells showed inhibition of phosphorylation of known PIM downstream targets, such as BAD and eukaryotic translation initiation factor 4E-binding protein 1, by K00135. (ox.ac.uk)
However, EGFR-tyrosine kinase inhibitor (TKI) alone or in combination therapy with paclitaxel or docetaxel had been used for breast cancer patients in clinical trials, but both therapies failed [ 2 ]. (biomedcentral.com)
The Parkinson's disease genes pink1 and parkin , which encode a mitochondrially targeted protein kinase, and an E3 ubiquitin ligase, respectively, participate in a key mitochondrial quality-control pathway that eliminates damaged mitochondria. (sdbonline.org)
Furthermore, BIMP increased the protein expressions and phosphorylation of BiP, CHOP, and protein kinase RNA-like ER kinase and the phosphorylation of eukaryotic translation initiation factor 2. (inra.fr)
CK2 (proteins kinase CK2) may phosphorylate eIF2 (eukaryotic translation initiation aspect 2) phosphorylation of eIF2 also pointed to Ser2 being a preferred site for CK2 phosphorylation. (bioinf.org)
The central/C-terminal locations also support the binding sites for CK2, whereas the phosphorylation sites because of this proteins kinase can be found in the N-terminal area. (bioinf.org)
The current presence of three lysine blocks and phosphorylation sites for proteins kinase CK2 and PKC (proteins kinase C) are quality from the N-terminal area of mammalian eIF2 [21]. (bioinf.org)
The websites phosphorylated on mammalian eIF2 have already been mapped at Ser2, Ser67 (both targeted by CK2), Ser13 (targeted by PKC) and Ser218 [targeted by PKA (proteins kinase A)] [21]. (bioinf.org)
eIF2 can be a substrate for DNA-PK (DNA proteins kinase) [24], even though the phosphorylation site(s) because of this kinase never have been identified however. (bioinf.org)
Background The serine-threonine protein kinase mammalian target of rapamycin (mTOR), which is definitely inhibited from the immunosuppressant drug rapamycin regulates several intracellular pathways in response to numerous extracellular signals, nutrient availability, energy status of the cell and stress. (researchensemble.com)
These pathways involve mTOR-dependent activation of the 70 kDa ribosomal protein S6 kinase (p70S6K) as well as the inactivation of the repressor of mRNA translation, eukaryotic initiation element 4E (eIF4E) binding protein (4EBP) [1,2]. (researchensemble.com)
GS-002 also induced endoplasmic reticular (ER) stress as evidenced by increases in ER stress-responsive proteins including glucose-regulated protein 78 (GRP78), growth arrest- and DNA damage-inducible gene 153 (GADD153), phosphorylated eukaryotic initiation factor 2 α (eIF2 α ), phosphorylated protein endoplasmic-reticular-resident kinase (PERK), and ATF-3. (hindawi.com)
The induction of ATF-3 expression was mediated by mitogen-activated protein kinase (MAPK) signaling pathways in GS-002-treated cells. (hindawi.com)
The UPR consists of three signaling pathways initiated by detachment of upstream transducers activating transcription factor 6 (ATF6), protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) and inositol-requiring enzyme 1 (IRE1) from glucose-regulated protein 78 (GRP78), a chaperone protein that monitors accumulation of unfolded and misfolded proteins inside the ER lumen. (londonspring.org)
2) PERK signaling consist of auto-phosphorylation of PERK (P-PERK), generating an active kinase that phosphorylates eukaryotic translation-initiation factor 2α (P-eIF2α). (londonspring.org)
Image analysis of the matched maps identified 7 proteins that were either over- or down-expressed: activated protein kinase c receptor (LACK), alpha tubulin (×2), prostaglandin f2-alpha synthase, protein disulfide isomerase, vesicular transport protein and a hypothetical protein. (who.int)
L'analyse d'image des cartes appariées a permis d'identifier sept protéines qui étaient soit surexprimées, soit sous-exprimées : le récepteur de la protéine kinase C activée, la tubuline alpha (×2), la prostaglandine F2-alpha synthase, la protéine disulfide isomérase, une protéine du transport vésiculaire et une protéine hypothétique. (who.int)
The class I PI3Ks are activated by growth factor tyrosine kinase receptors (class IA), such as EGFR, or by G protein coupled receptors (GPCRs) (class IB). (ebrary.net)
Subsequently, mTOR phosphorylates key eukaryotic translation regulators, including p70-S6 kinase (p70S6K) and the eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) (Hay and Sonenberg 2004). (ebrary.net)
In the UPR, the sensor proteins are the kinase PERK and the kinase/endoribonuclease IRE1 work together to recognize and respond to unfolded proteins. (ucsb.edu)
Here, we show that eIF4A1, but not eIF4A2, enhances translational repression during the inhibition of mechanistic target of rapamycin complex 1 (mTORC1), an essential kinase complex controlling cell proliferation. (biorxiv.org)
Further mechanistic studies revealed that these functions were controlled by the eukaryotic initiation factor (eIF) 4E and the mitogen-activated protein kinase (MAPK) interacting protein kinase (MNK) signaling pathways, which regulate which mRNAs will be translated. (lu.se)

Specifically, blocking MNK2 interaction with eIF4G has been shown to boost protein synthesis and promote beta cell regeneration. (wikipedia.org)
These results indicate that in infected cells, gamma(1)34.5 interacts with and redirects phosphatase to dephosphorylate eIF-2alpha to enable continued protein synthesis despite the presence of activated PKR. (scienceopen.com)
The proposed mechanism for maintenance of protein synthesis in the face of double-stranded RNA accumulation is different from that described for viruses examined to date. (scienceopen.com)
Endoplasmic reticulum stress (ERS) is a state induced by increased synthesis of intracellular proteins, accumulation of mal-folded proteins, changes in cytosolic calcium levels, or imbalances in endoplasmic reticulum (ER) redox homeostasis [ 8 ]. (biomedcentral.com)
Functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. (nih.gov)
The translation initiation factor EIF2 catalyzes the first regulated step of protein synthesis initiation, promoting the binding of the initiator tRNA to 40S ribosomal subunits. (nih.gov)
In many cell lines, exposure to rapamycin results in a relatively small decrease in overall protein synthesis (~15-20%), but dose result specifically in G1 cell cycle arrest. (biomedcentral.com)
Inadequate fine-tuning of protein synthesis and failure of amino acid homeostasis following inhibition of the ATPase VCP/p97. (ox.ac.uk)
VCP inhibition had an impact on two key regulators of protein synthesis, eukaryotic initiation factor 2α (eIF2α) and mechanistic target of rapamycin complex 1 (mTORC1), and attenuated global protein synthesis. (ox.ac.uk)
Thus, cancer cell death following VCP inhibition was linked to inadequate fine-tuning of protein synthesis and activity of PPP1R15A/PP1c. (ox.ac.uk)
Thus, depletion of VCP enzymatic activity triggers cancer cell death in part through inadequate regulation of protein synthesis and amino acid metabolism. (ox.ac.uk)
Phosphorylation of eIF2α on Ser51 inhibits 5' cap-dependent mRNA translation, resulting in the global suppression of protein synthesis to facilitate adaptation to a variety of stresses linked to protein synthesis, including proteotoxic stress, viral replication, heme depletion and amino acid withdrawal [ 2 ]. (biomedcentral.com)
The eIF2α kinases phosphorylate Ser51 of eIF2α which leads to suppression of global protein synthesis but selective enhancement of translation of some mRNAs, such as that encoding ATF4. (biomedcentral.com)
Preliminary studies for the practical outcomes of mammalian eIF2 phosphorylation for proteins synthesis showed it Formoterol supplier did not influence the power of eIF2 to create the ternary complicated with GTP and Met-tRNAiMet [33]. (bioinf.org)
In today's work, we researched the phosphorylation of individual eIF2 as well as the relevance of the primary phosphorylation sites and of the complete N-terminal site of eIF2 in its discussion with some companions, in proteins synthesis and in cell viability. (bioinf.org)
Summary We conclude that mTOR has a part in maintaining prolonged pain claims via mRNA translation and thus protein synthesis. (researchensemble.com)
Nevertheless, to time, few have looked into the function of vertebral proteins synthesis pathways in consistent pain-like state governments. (researchensemble.com)
Kim and co-workers show that proteins synthesis can be an important element of the behavioural hypersensitivity induced by shot of formalin in to the hind paw of mice. (researchensemble.com)
ATF-3 induces DNA synthesis and expression of cyclin D1 in hepatocytes [ 21 ] and is involved in serum-induced cell proliferation as a target gene of c-myc [ 10 ]. (hindawi.com)
Eukaryotic translation initiation factor 2 (EIF-2) functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA and binding to a 40S ribosomal subunit. (thermofisher.com)
While AKT phosphorylates multiple downstream targets (see above), the emerging picture is that the ability of AKT to coordinate mitogenic and nutrient-sensing pathways controlling protein synthesis is a key mechanism by which AKT regulates cell proliferation. (ebrary.net)
They both exert regulatory control by shutting down protein synthesis, turning on genes, and degrading transcripts. (ucsb.edu)
Activation of PERK elicits a transient global protein synthesis shutdown through the phosphorylation of the alpha subunit of the eukaryotic translation initiation factor 2 (eIF2α). (ucsb.edu)
Our data show that the distinct protein interactions of these highly homologous translation factor paralogs shape protein synthesis during mTORC1 inhibition and provide a unique example of the repressive role of a universal translation activator. (biorxiv.org)

3 In that clinical trial, some clinical responses associated with the reduction of eukaryotic translation initiation factor 4E (eIF4E) levels were seen. (haematologica.org)
Phosphorylation by mTOR of 4E-BP1 disrupts its binding to eIF4E, a protein that binds the 5'-cap structure of mRNA. (biomedcentral.com)
Whether translation initiation factor 4E (eIF4E), the mRNA cap binding and rate-limiting factor required for translation, is a target for cytotoxicity and cell death induced by cadmium , a human carcinogen, was investigated. (cdc.gov)
Exposure of human cell lines, HCT15, PLC/PR/5, HeLa, and Chang, to cadmium chloride resulted in cytotoxicity and cell death, and this was associated with a significant decrease in eIF4E protein levels. (cdc.gov)
Further studies revealed the absence of alterations in the eIF4E mRNA level in the cadmium -treated cells despite their decreased eIF4E protein level. (cdc.gov)
In addition, exposure of cells to cadmium resulted in enhanced ubiquitination of eIF4E protein while inhibitors of proteasome activity reversed the cadmium -induced decrease of eIF4E protein. (cdc.gov)
Taken together, our results demonstrate that the exposure of cells to cadmium chloride resulted in cytotoxicity and cell death due to enhanced ubiquitination and consequent proteolysis of eIF4E protein, which in turn diminished cellular levels of critical genes such as cyclin D1. (cdc.gov)
The latter overrides the repressing activity of 4E-BP1 on the eukaryotic initiation factor 4E (eIF4E), resulting in enhanced translation of a subset of growth promoting genes (Hay and Sonenberg 2004). (ebrary.net)

and (iii) the alpha subunit in purified eIF-2 phosphorylated in vitro is specifically dephosphorylated by S10 fractions of wild-type infected cells at a rate 3000 times that of mock-infected cells, whereas the eIF-2alpha-P phosphatase activity of gamma(1)34.5- virus infected cells is lower than that of mock-infected cells. (scienceopen.com)
Growth arrest and DNA damage-inducible protein GADD34 targets protein phosphatase 1 alpha to the endoplasmic reticulum and promotes dephosphorylation of the alpha subunit of eukaryotic translation initiation factor 2. (scienceopen.com)
This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S pre-initiation complex. (nih.gov)
Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF-2 and release of an eIF-2-GDP binary complex. (nih.gov)
In most metazoans, GCN2 is one of the four known kinases that phosphorylate eukaryotic initiation factor 2, α subunit (eIF2α) to inhibit translation initiation [ 19 ]. (biomedcentral.com)
Some of the proteotoxic effects of VCP depletion depended on the eIF2α phosphatase, protein phosphatase 1 regulatory subunit 15A (PPP1R15A)/PP1c, but not on mTORC1, although there appeared to be cross-talk between them. (ox.ac.uk)
PERK (EIF2AK3) is the third UPR sensor, which phosphorylates the subunit of eukaryotic initiation Benzylpenicillin potassium factor 2 (eIF2) to direct translational and transcriptional modes of gene expression that regulate ER processing of proteins, metabolism, and the oxidation status of cells (6, 10). (iwap2018.com)
An important functional component of hemidesmosomes is the integrin beta-4 subunit (ITGB4), a protein containing two fibronectin type III domains. (absave.com)
catalytic subunit of CK2 (CK2) inhibits its activity in proteins substrates [16]. (bioinf.org)
EXPERIMENTAL Reagents and antibodies Apigenin, emodin and anti-His6 antibody had been extracted from Sigma, anti-eIF2 as well as the catalytic subunit from the PP2A (proteins phosphatase 2A) phosphatase had been from Cell Signaling Technology, anti-CK2 and anti-eIF5 had been from Santa Cruz Biotechnology and anti-eIF2 was from Cell Signaling Technology. (bioinf.org)
EIF-2 is composed of three subunits, alpha, beta, and gamma, with the protein encoded by this gene representing the beta subunit. (thermofisher.com)
The beta subunit catalyzes the exchange of GDP for GTP, which recycles the EIF-2 complex for another round of initiation. (thermofisher.com)

The anti-eIF2 antibody grew up in rabbits immunized using the recombinant proteins, as well as the immunoglobulin small fraction was extracted from Formoterol supplier sera by Proteins ACagarose Formoterol supplier chromatography (Amersham Biosciences). (bioinf.org)
P-eIF2α blocks its translation initiating activity and induces ATF4 phosphorylation (P-ATF4) leading to P-ATF4 nuclear translocation as a transcription factor to induce expression of GRP78, C/EBP homologous protein (CHOP), XBPu etc. (londonspring.org)
Active PKR phosphorylates the same residue targeted by PERK on eIF2α, while active RNaseL degrades RNAs. (ucsb.edu)

3) IRE1α signaling includes IRE1α phosphorylation (P-IRE1α), an active endonuclease that cleaves XBP-1u mRNA to XBP-1s mRNA, which is then translated to an active transcription factor to induce UPR target genes encoding GRP78, ERAD proteins etc. (londonspring.org)
A second activation-specific AKT phosphorylation in serine 473 (pAKT S473 ) is targeted by mTOR as part of its complex 2 (mTORC2) (Sarbassov et al. (ebrary.net)
AKT phosphorylation and inactivation of TSC2 results in increased levels of the GTP-bound (active) form of Rheb1, which in turn promotes the phosphorylation and activation of mTOR, also known as the mammalian target of rapamycin (Manning and Cantley 2003). (ebrary.net)

EIF5B (Eukaryotic Translation Initiation Factor 5B) is a conserved eukaryotic translation factor that mediates association of the 40S and 60S ribosomal subunits during eukaryotic translation initiation, and modulates the cell cycle progression by regulating the translation of upstream open reading frames (uORF)-containing mRNAs such as p27 and p21 [ 3 ]. (techscience.com)

AKT prevents cell death by inactivating proapoptotic factors including BAD, procaspase-9 and Forkhead transcription factor family proteins (FOXOs), activates transcription factors that upregulate antiapoptotic genes, including NF-kB, inactivates p53 through Mdm2, and phosphorylates the cell cycle inhibitors p21 CIP1/WAF1 and p27 KIP1 , thus increasing cell proliferation (Hennessy et al. (ebrary.net)

MNK2 has been shown to interact with MAPK1 and Eukaryotic translation initiation factor 4 gamma. (wikipedia.org)
Heterogeneous population of RNA granules serve as motile units to translocate, store, translate, and degrade mRNAs in the dendrites contain cis -elements and trans -acting factors such as RNA-binding proteins and microRNAs to convey stimulus-, transcript-specific local translation. (frontiersin.org)
The existence of mRNAs retaining both nuclear cap binding protein and EJC in the distal sites of neuronal processes suggests that some localized mRNAs have not yet undergone the "very first translation," which contribute to the spatio-temporal regulation of gene expression. (frontiersin.org)
Specifically, the PDCD4 protein combines directly with the mRNA coding region of the target gene ( MYB/c-MYB ) to block translation [2] . (plos.org)
It can also compete with eukaryotic translation initiation factor (eIF)4G and RNA for eIF4A binding and trap eIF4A in an inactive conformation to inhibit translation initiation via its two highly conserved MA3 domains [3] - [6] . (plos.org)
In this issue of the JCI, Maier and colleagues identify eukaryotic translation initiation factor 5A (eIF5A) as a critical regulator of the inflammatory response in mouse pancreatic islets. (jci.org)
4EBP1, eukaryotic translation initiation factor 4E binding protein 1. (medlink.com)
This was followed by sustained MTOR (mechanistic target of rapamycin) activation, with enlarged cell size, glucose uptake and translation, which is detrimental to the quiescent HSCs. (ox.ac.uk)
Eukaryotic translation initiation factors (eIFs) are crucial in the initiation of protein translation. (cbmed.at)
Protein biosynthesis can directly target the translation of specific mRNA and foster cell viability, invasion, formation of metastasis and tumor proliferation. (cbmed.at)
Influence of eukaryotic translation initiation factor 6 (eIF6) on non-small lung cancer development and progression. (cbmed.at)
In the glioma cells, EIF5B promotes cell survival by enhancing the translation of several IRES-containing mRNAs including those encoding anti-apoptotic proteins such as XIAP and Bcl-xL [ 4 ]. (techscience.com)
However, a block on protein translation that was itself cytotoxic alleviated stress signaling and reduced cell death triggered by VCP inhibition. (ox.ac.uk)
The encoded protein, which is insoluble and found both in the nucleus and in the cytoplasm, can function as a translation initiation factor and prevent the association of the 40S and 60S ribosomal subunits. (absave.com)
Their studies centered on mice missing delicate mental retardation gene (FMR1), which is another proteins that affects translation mRNA. (researchensemble.com)
Eukaryotic translation initiation factor 4E is a cellular target for toxicity and death due to exposure to cadmium chloride. (cdc.gov)
LINC00659 knock-down promoted the proliferation, migration, and angiogenesis ability of EPCs, while an pcDNA-eukaryotic translation initiation factor 4A3 (EIF4A3), a EIF4A3 overexpression vector, or fibroblast growth factor 1 (FGF1) small interfering RNA (siRNA) combined with LINC00659 siRNA could not enhance this effect. (biomedcentral.com)
This event leads to the paradoxical translation of a few select mRNAs that contain regulatory upstream open reading frames (uORFs), such as the mRNAs encoding the transcription factors ATF4 and CHOP. (ucsb.edu)
Eukaryotic translation initiation factor (eIF) 4A - a DEAD-box RNA-binding protein - plays an essential role in translation initiation. (biorxiv.org)

1 Protein Kinases and Signal Transduction Laboratory, Departament De Bioquímica I Biologia Molecular and Institut De Neurociències, Universitat Autònoma De Barcelona (UAB), Barcelona, Spain. (nih.gov)
Targeted inhibition of individual kinases of the MAPK signaling pathway using synthetic compounds represents a promising way to effective anti-cancer therapy. (mdpi.com)
Much attention has recently been focused on PIM kinases as potential targets for the treatment of hematopoietic malignancies and some solid cancers. (ox.ac.uk)
Using protein stability shift assays, we identified a family of imidazo[1,2-b]pyridazines to specifically interact with and inhibit PIM kinases with low nanomolar potency. (ox.ac.uk)
Taken together, we report a family of small molecules that selectively interact and block PIM kinases and could serve as a lead to develop new targeted antileukemic therapeutics. (ox.ac.uk)

Features of signaling through the mammalian target of rapamycin complex 1 pathway via the tuberous sclerosis 1/tuberous sclerosis 2 complex. (medlink.com)
RAD001 (everolimus), a mammalian target of rapamycin (mTOR) pathway inhibitor in phase II clinical trials in oncology, exerts potent antiproliferative/antitumor activities. (aacrjournals.org)

Endoplasmic reticulum stress (ERS) is a self-protective mechanism resulting from an imbalance in quality control of unfolded proteins when cells are stressed, which plays an active role in lung cancer development, but the relationship between ERS and the pathological characteristics and clinical prognosis of LUAD patients remains unclear. (biomedcentral.com)
The unfolded protein response (UPR) is a major mechanism that detects and alleviates protein-folding stresses in the endoplasmic reticulum. (elifesciences.org)
The endoplasmic reticulum (ER) is the major subcellular compartment that is involved in protein folding and secretion. (elifesciences.org)
Here, we show that triggers the unfolded protein response (UPR) in host cells through calcium release from the endoplasmic reticulum (ER). (iwap2018.com)
Recent research demonstrated that the potential to induce apoptosis through endoplasmic reticular (ER) stresses can be a target for cancer therapy. (hindawi.com)
Endoplasmic Reticulum (ER) homeostasis/stress and the unfolded protein response (UPR) signaling in physiopathologic conditions. (londonspring.org)
The Unfolded Protein Response (UPR) , the stress response network of the endoplasmic reticulum (ER), exquisitely illustrates this concept. (ucsb.edu)

Cox regression analysis identifies independent prognostic factors for these patients, and enrichment analysis of prognosis-related genes was also performed. (biomedcentral.com)
In the subset of VPA targeted genes, 114 were downregulated whilst 217 genes were upregulated. (plos.org)
In the subset of LiCl targeted genes, 73 were downregulated and 91 were upregulated. (plos.org)
In response to ER stress, ATF6 transits from the ER to the Golgi apparatus, where it is cleaved, releasing an N-terminal cytosolic fragment (ATF6-N) that enters the nucleus and activates UPR target genes involved in protein folding and transport (6, 9). (iwap2018.com)
Treatment with BIMP increased the mRNA levels of the ER stress marker genes binding immunoglobulin protein (BiP) and the transcription factor C/EBP homologous protein (CHOP). (inra.fr)

Through this interaction, mRNAs and their associative proteins form messenger ribonucleoprotein particles (mRNPs) that are actively transported along the cytoskeleton to intracellular destinations. (frontiersin.org)

The carboxyl-terminal 64 aa of gamma(1)34.5 protein are homologous to the corresponding domain of MyD116, the murine growth arrest and DNA damage gene 34 (GADD34) protein and the two domains are functionally interchangeable in infected cells. (scienceopen.com)
Description of the protein which includes the UniProt Function and the NCBI Gene Summary. (nih.gov)
Gene symbols, accession ids and various other target identifiers. (nih.gov)
Total count of NCBI Gene Reference Into Function hits for target listed in parenthesis, and summary table with links to publications per PMID with the specific text in article that includes the reported target. (nih.gov)
Three Benzylpenicillin potassium ER transmembrane proteins, IRE1, ATF6, and PERK, operate as sensors that activate the UPR, leading to changes in gene expression that restore and expand the processing capacity of the organelle (6,C8). (iwap2018.com)
The protein encoded by this gene binds to the fibronectin type III domains of ITGB4 and may help link ITGB4 to the intermediate filament cytoskeleton. (absave.com)
The ornithine decarboxylase gene is a transcriptional target of c-Myc. (idrblab.net)
An essential E box in the promoter of the gene encoding the mRNA cap-binding protein (eukaryotic initiation factor 4E) is a target for activation by c-myc. (idrblab.net)
To implement effective RNAi against A. flavus requires identification of suitable gene target/s that are critical for fungal growth and aflatoxin production. (usda.gov)
Comprehensive gene expression programs are subsequently initiated, allowing the cell to either resolve the protein folding stress or die trying. (ucsb.edu)

ABSTRACT In order to define the protein expressional changes related to the process of meglumine antimoniate resistance in anthroponotic cutaneous leishmaniasis (CL), we performed a comparative proteomics analysis on sensitive and resistant strains of Leishmania tropica isolated from Iranian CL patients. (who.int)

Autophagy dysfunction results in the accumulation of intracellular damaged proteins, causing neurodegeneration or cardiac hypertrophy [ 4 ]. (biomedcentral.com)

Cross-talk of the MAPK signaling pathway with other proteins and signaling pathways have a crucial impact on clinical outcomes of targeted therapies and plays important role during development of drug resistance in cancers. (mdpi.com)
The integrated stress response (ISR) is an adaptive signaling pathway that contributes to the biology of a number of hematologic malignancies since they are inherently prone to numerous cellular stresses [ 2 ]. (biomedcentral.com)
The ISR (Fig. 1 ) is a complex signaling pathway that regulates cellular responses to stress stimuli and enables either adaptation or the instigation of cell death mechanisms [ 2 ]. (biomedcentral.com)

Treating SMMC-7721 cells with Rapamycin, a specific mTOR inhibitor, significantly reduce hTERT protein level but did not affect hTERT transcription. (biomedcentral.com)
Several molecular targets have been tested in clinical trials and this chapter presents novel research on the efficacy of mTOR inhibition in cancer treatment and prevention. (ebrary.net)

As depicted in Fig. 7.1, AKT phosphory- lates and inactivates the tumor-suppressor protein tuberous sclerosis complex protein 2 (TSC2), which forms a complex with tuberous sclerosis complex protein 1 (TSC1), and act together as a GTPase activating protein (GAP) for the small GTPase Rheb1 (Inoki et al. (ebrary.net)

I believe these data provide new and important insights into the regulatory pathways that contribute to the development of diabetes and deepen our understanding of the function of the, so far, rather enigmatic cellular protein eIF5A. (jci.org)
The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
DR acts by promoting stress response pathways and preventing age-related functional decline, delaying the appearance of cardiovascular diseases, type 2 diabetes, and neurodegeneration in mammals, including non-human primates [ 6 ]. (biomedcentral.com)
p97) is an essential regulator of protein degradation in multiple pathways and has emerged as a target for cancer therapy. (ox.ac.uk)
Some of these natural mushroom compounds have demonstrated specific activity against signaling pathways that are aberrantly activated in cancer cells and have been shown to negatively modulate specific molecular targets involved in cell proliferation, survival, and angiogenesis [ 10 ] [ 11 ] . (encyclopedia.pub)
Targeted therapies exploit molecular vulnerabilities unique to cancer cells and typically alter cellular signaling pathways to inhibit tumorigenic growth and promote cell death. (biomedcentral.com)
Therefore, an improved understanding of the molecular signaling pathways modulated by targeted therapies is critical to enhancing the efficacy of these agents. (biomedcentral.com)
2006). In turn AKT plays a key role in the transmission of pro-proliferative and transforming pathways initiated by EGFR and multiple growth factor receptors, as well as by oncogenic active PI3K mutants (Luo et al. (ebrary.net)

ABTL0812 is a first-in-class small molecule with anti-cancer activity, which is currently in clinical evaluation in a phase 2 trial in patients with advanced endometrial and squamous non-small cell lung carcinoma ( NCT03366480 ). (nih.gov)
Given the fact that ABTL0812 is under clinical development, our findings support the hypothesis that manipulation of dihydroceramide levels might represents a new therapeutic strategy to target cancer. (nih.gov)
The authors point out that while clinical studies that target components of the tumor microenvironment in this setting are still limited, the integration of preclinical findings described here may help facilitate novel clinical strategies for the prevention and treatment of brain metastases. (aacr.org)
Progress in genetic analyses have advanced our understanding of the molecular drivers underpinning hematologic malignancies, thus prompting the development of an array of targeted therapies that are revolutionizing the clinical management of these diseases [ 1 ]. (biomedcentral.com)
based on a number of pathologic, physiologic, and clinical factors. (msdmanuals.com)
ER protein determinations were performed using two-thirds of all breast cancers are ER at the time of diagnosis, the standard methods in the routine clinical laboratory (9). (lu.se)

The introduction of vismodegib, which targets glioma-associated protein 1 (GLI1) through the Smoothened receptor (Smo), was based on the novel discovery by this group that UDP-glucuronosyltransferase 1 A (UGT1A) and GLI1 have increased expression in resistant AML cells and induce glucuronidation of ribavirin and cytarabine. (haematologica.org)
However, if the stress on the ER is chronic or severe and quality control of protein folding cannot be met, ER activates its stress receptor, the unfolded protein response, which triggers programmed cell death [ 9 ]. (biomedcentral.com)
PTPRC/CD45: Protein Tyrosine Phosphatase Receptor Type C, CD45 antigen. (ox.ac.uk)
Ligand-dependent activation of the G-protein coupled receptor 119 (GPR119) lowers blood glucose via glucose-dependent insulin secretion and intestinal glucagon-like peptide-1 production. (biomedcentral.com)
Anti-epidermal growth factor receptor (EGFR) therapy is an effective way to inhibit proliferation of many cancer types such as non-small cell lung cancer (NSCLC) and colorectal cancer [ 1 ]. (biomedcentral.com)

Using EBNA3C amino acids 365-545 in a yeast two hybrid screen, we found an interaction with the Growth Arrest and DNA-damage protein, Gadd34. (scienceopen.com)

In preclinical models utilizing human lung cancer cells and specific NSCLC mutational subsets, the researchers found that tumor growth was enhanced by anti-PD-1 treatment but not by anti-PD-1 F(ab) 2 fragments, which lack the Fc portion of the antibody. (aacr.org)
eIFs are promising targets for several tumor entities and could be used in cancer therapy and as potential prognostic biomarkers. (cbmed.at)
Therefore, EMT-targeted therapy is necessary to effectively overcome tumor drug resistance and recurrence. (techscience.com)
In addition, there are non-cellular components such as growth factors, cytokines, and extracellular matrix that surround the tumor cells. (biomedcentral.com)
They are responsible for the regulation of various pro- and anti-tumor factors and play a role in the progression of the disease. (biomedcentral.com)
Our research primarily focuses on tumor immunology, with a particular emphasis on understanding the behavior of Tumor-Associated Macrophages (TAMs) and is dedicated to finding novel targets that reprogram immunosuppressive and pro-metastatic Tumor-Associated Macrophages into an anti-tumor phenotype. (lu.se)
Figure 1: Finding Novel Targets that Reprogram the Immunosuppresive Tumor Microenvironment (TME). (lu.se)

Activating transcription factor-(ATF-) 3, a stress-inducible transcription factor, is rapidly upregulated under various stress conditions and plays an important role in inducing cancer cell apoptosis. (hindawi.com)

In the present study, we demonstrate that IRE1α (also known as ERN1) and its downstream target, XBP1, are activated in skeletal muscle of mice upon injury. (elifesciences.org)
Deviations from homeostasis are quickly and effectively identified by specialized sensor proteins that relay information to downstream effectors, which initiate appropriate actions to restore homeostasis. (ucsb.edu)

In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF-2 must exchange with GTP by way of a reaction catalyzed by eIF-2B. (nih.gov)

Expression of the L1 protein using recombinant DNA technology produces noninfectious virus-like particles (VLPs). (cdc.gov)

Deregulated protein biosynthesis contributes to carcinogenesis and the progression of cancer. (cbmed.at)
The major risk factors associated with HCC development and progression include chronic hepatitis B or C virus infections, high alcohol consumption, and activation of oncogenes [ 2 ]. (techscience.com)
Additionally, the TME is influenced by m 6 A regulatory factors, impacting the progression and prognosis of CRC. (biomedcentral.com)
The elucidation of the dysregulated molecular mechanisms driving HNSCC progression may afford a unique opportunity to identify novel targeted treatment options for HNSCC therapy and prevention. (ebrary.net)

Biosynthesis of spermidine (Spd) is critical for cell growth as it is required for hypusination-mediated activation of eukaryotic initiation (translational) factor 5A (eIF5A). (usda.gov)

MNK2 has been identified as a therapeutic target for diabetes. (wikipedia.org)
Our data suggested that EIF5B is a promising prognostic biomarker and therapeutic target in HCC. (techscience.com)
The cellular mechanisms that control protein degradation may constitute a non-oncogenic cancer cell vulnerability and, therefore, a therapeutic target. (ox.ac.uk)
Therapeutic Target Database describing target druggability information. (idrblab.net)
A database to provide information about the known and explored therapeutic protein and nucleic acid targets, the targeted disease, pathway information and the corresponding drugs directed at each of these targets. (idrblab.net)
thus, indicating the therapeutic potential of ISR modulation as a strategy for improving the efficacy of targeted therapies. (biomedcentral.com)
We also discuss the evidence for the emerging role of the ISR in mediating the efficacy of targeted therapies and the significance of these findings for developing new therapeutic approaches for hematologic malignancies. (biomedcentral.com)
In summary, the data indicated the roles of LINC00659 in the pathogenesis of LEDVT, and the LINC00659/EIF4A3/FGF1 axis could be a novel therapeutic target for the treatment of LEDVT. (biomedcentral.com)

With purified protein and soluble substrates, the exoglucanase activity of the GH7 domain embedded in the Fusion 3 construct in L. starkeyi was significantly higher than that of the GH7 domain in TeTr CBHI expressed alone. (biomedcentral.com)

Higher GRP78 affinity for unfolded/misfolded proteins dissociates GRP78 from ATF6, PERK and IRE1, enabling GRP78 unfolded/misfolded protein binding that then initiates three UPR signaling cascades. (londonspring.org)
Sensors and effectors are coupled as specific domains of single proteins in PERK, PKR and IRE1. (ucsb.edu)

Impt-1 knockdown exacerbated DR-induced longevity and required several DR-activated transcription factors to extend lifespan, among them SKN-1 and DAF-16, which were induced during larval development and adulthood, respectively, in response to impt-1 RNAi. (biomedcentral.com)

The study shows the usefulness of proteomics in identifying proteins that may express differences between sensitive and resistant L. tropica isolates. (who.int)

DHS has been efficiently targeted by low-molecular-weight drugs, such as the spermidine analogue GC7 ( 24 ) and the multivalent guanylhydrazone CNI-1493 ( 14 ). (jci.org)
This review aims to provide new insights into the molecular targets and theoretical foundations for the treatment of CRC. (biomedcentral.com)

Estrogens are important regulators of growth and differentiation in (range, 0 -9 fmol/mg protein, median 0.7). (lu.se)

Using a wide range of biochemical and lipidomic analyses, we demonstrated that ABTL0812 increases cellular long-chain dihydroceramides by impairing DEGS1 (delta 4-desaturase, sphingolipid 1) activity, which resulted in sustained ER stress and activated unfolded protein response (UPR) via ATF4-DDIT3-TRIB3 that ultimately promotes cytotoxic autophagy in cancer cells. (nih.gov)
ChIP-QPCR analysis revealed that ATF4, an ER-stress inducible transcription factor, directly activated Zbtb38 transcription by binding to the Zbtb38 promoter. (oncotarget.com)

The eIF-2alpha-P phosphatase activities are sensitive to inhibitor 2. (scienceopen.com)

Bioinformatics analysis demonstrated that the EIF5B transcript and protein levels as well as the EIF5Bcopy number were significantly higher in the HCC tissues compared with the non-cancerous liver tissues. (techscience.com)

Finally, targeted ablation of IRE1α also reduces Notch signaling, abundance of satellite cells, and skeletal muscle regeneration in the mdx mice, a model of Duchenne muscular dystrophy. (elifesciences.org)
C) Lysates were prepared from the cells and IRE1, GFP, or actin protein levels were measured by immunoblot analyses using specific antibodies. (iwap2018.com)
We further identify a novel role for the host ER stress sensor protein IRE1 in pathogenesis. (iwap2018.com)
On the other hand, activation of IRE1 results in the production of the transcription factor XBP1 through a well-understood unconventional splicing mechanism. (ucsb.edu)

Finally, we identified that EV-associated enolase was resistant to SpeB degradation, and therefore could be utilized as the internal control protein for verifying SLO degradation. (bvsalud.org)
This study revealed that RopB would participate in modulating protein composition in EVs via SpeB-dependent protein degradation and suggested that enolase is a potential internal marker for studying GAS EVs. (bvsalud.org)

DHS catalyzes the transfer of the aminobutyl moiety of the polyamine spermidine to the ε-NH 2 group of Lys50 in the inactive eIF5A precursor protein. (jci.org)

The ER is sensitive to the perturbations in protein homeostasis through a stress-sensing pathway known as the unfolded protein response (UPR). (iwap2018.com)

In this review, we discuss the role of the integrated stress response in the biology of hematologic malignancies, its critical involvement in the mechanism of action of targeted therapies, and as a target for pharmacologic modulation as a novel strategy for the treatment of hematologic malignancies. (biomedcentral.com)

Methionine is an essential amino acid, that affects the metabolism of protein, lipid and glucose. (researchsquare.com)

Specifically: (1) ATF6 signaling involves its translocation to Golgi apparatus for proteolytic cleavage by site-1 protease (S1P) and site-2 protease (S2P) and subsequent release into the nucleus as an active transcription factor to induce expression of GRP78, ubiquitously expressed X-box binding protein 1 (XBP1u) etc. (londonspring.org)

Anatomy21

Organisms17

Diseases1

Chemicals and Drugs121

Analytical, Diagnostic and Therapeutic Techniques and Equipment24

Phenomena and Processes60

Disciplines and Occupations1

Technology, Industry, Agriculture1

Information Science3

Health Care1

Kinase33

Synthesis24

EIF4E8

Subunit12

EIF23

Phosphorylation3

Conserved eukaryotic translation1

Phosphorylates1

Translation19

Kinases5

Mammalian2

Endoplasmic7

Genes5

MRNAs1

Gene10

Abstract1

Intracellular1

Signaling pathway3

MTor2

Tuberous scleros1

Pathways8

Clinical6

Receptor5

Amino Acids1

Tumor7

Apoptosis1

Downstream2

Another round of initiation1

Recombinant1

Progression4

Translational1

Therapeutic8

Substrates1

PERK2

Transcription factors1

Proteomics1

Molecular2

Regulators1

ATF42

Inhibitor1

Bioinformatics1

IRE14

Degradation2

EIF5A1

Homeostasis1

Mechanism1

Metabolism1

GRP781