AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPsychiatry and PsychologyPhenomena and ProcessesDisciplines and OccupationsInformation Science
UbiquitinUbiquitin-Protein LigasesUbiquitinsLigasesUbiquitin-Conjugating EnzymesUbiquitinationEndosomal Sorting Complexes Required for TransportProteasome Endopeptidase ComplexAngelman SyndromeUbiquitin-Activating EnzymesPolyubiquitinSKP Cullin F-Box Protein LigasesUbiquitin-Protein Ligase ComplexesUbiquitin ThiolesteraseMolecular Sequence DataAnaphase-Promoting Complex-CyclosomeAmino Acid SequenceProtein Sorting SignalsSignal TransductionHydroxyapatitesCysteine EndopeptidasesMultienzyme ComplexesSaccharomyces cerevisiae ProteinsProtein BindingMutationSaccharomyces cerevisiaeSubstrate SpecificityInhibitor of Apoptosis ProteinsRecombinant Fusion ProteinsCullin ProteinsCell LineSequence Homology, Amino AcidCell Cycle ProteinsBase SequenceProteinsUbiquitin CF-Box ProteinsProtein Structure, TertiaryProteolysisRING Finger DomainsUbiquitinated ProteinsCarrier ProteinsS-Phase Kinase-Associated ProteinsLysineProtein Processing, Post-TranslationalHeLa CellsUbiquitin-Specific ProteasesAmino Acid MotifsHEK293 CellsModels, BiologicalProtein TransportProto-Oncogene Proteins c-cblDNA-Binding ProteinsEndopeptidasesPhosphorylationAdaptor Proteins, Signal TransducingNuclear ProteinsSignal Processing, Computer-Assistedbeta-Transducin Repeat-Containing ProteinsCarbon-Nitrogen LyasesModels, MolecularTranscription FactorsProteasome InhibitorsTransfectionCells, CulturedNuclear Localization SignalsBinding SitesMembrane ProteinsLeupeptinsSUMO-1 ProteinImmunoprecipitationTwo-Hybrid System TechniquesProtein StabilityMultiprotein ComplexesRNA, MessengerRecombinant ProteinsGene Expression RegulationPeptide HydrolasesCloning, MolecularBlotting, WesternCell NucleusSequence AlignmentSmall Ubiquitin-Related Modifier ProteinsTranscription, GeneticCOS CellsCell Line, TumorRepressor ProteinsIntracellular Signaling Peptides and ProteinsRNA InterferenceRNA, Small InterferingProto-Oncogene Proteins c-mdm2Protein Interaction Domains and MotifsEndoplasmic ReticulumProtein ConformationTime FactorsImmunoblottingSumoylationPlasmidsApoptosisThiolester Hydrolases
LigasePathwaysLigasesReceptorsDegradationPathwayReceptorMitogen-activaUbiquitinationHomeostasisRegulatesRegulationEGFRKinaseEndocytosisAdaptorProteasomeSynaptic proteinsIntracellularMAPKEndoplasmic reticulumCytoplasmicMechanismsYeastVesicleProcessesSpecificityMembrane proteinsMass spectrometryMoleculeExtracellularEndosomal SortingTumorRoleProteaseVacuolarTransmembraneAxonalStabilityMechanismMitochondriaDeubiquitinaseMTORMorphologyPhysiologicalPeptidesMitochondrialDownstreamUbiquitylationViral proteinsGenesEndosomeMembranesCompartmentsGPCRGeneModificationResponsesSkeletalMutationTissuesLipid
Ligase16
  • A ubiquitin ligase (also called an E3 ubiquitin ligase) is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin from the E2 to the protein substrate. (wikipedia.org)
  • In simple and more general terms, the ligase enables movement of ubiquitin from a ubiquitin carrier to another thing (the substrate) by some mechanism. (wikipedia.org)
  • The ubiquitin ligase is referred to as an E3, and operates in conjunction with an E1 ubiquitin-activating enzyme and an E2 ubiquitin-conjugating enzyme. (wikipedia.org)
  • citation needed] The ubiquitylation reaction proceeds in three or four steps depending on the mechanism of action of the E3 ubiquitin ligase. (wikipedia.org)
  • The E3 ubiquitin ligase XBAT35.2 can ubiquitinate and modify VPS23A to promote its entry into the 26S proteasome for degradation, thereby positively regulating the ABA signaling pathway. (phys.org)
  • Therefore, the E3 ubiquitin ligase XBAT35.2 and the deubiquitinating enzymes UBP12 and UBP13 act as accelerators and brakes that balance VPS23A ubiquitination homeostasis at different environments . (phys.org)
  • Unexpectedly, in addition to VPS23A, the researchers further found that the E3 ubiquitin ligase XBAT35.2 of VPS23A is also a substrate of UBP12 and UBP13. (phys.org)
  • Guangchao Liu et al, The deubiquitinases UBP12 and UBP13 integrate with the E3 ubiquitin ligase XBAT35.2 to modulate VPS23A stability in ABA signaling, Science Advances (2022). (phys.org)
  • Regulation of PTEN/Akt and MAP kinase signalling pathways by the ubiquitin ligase activators Nfip1 and Ndfip2. (cam.ac.uk)
  • Some of these proteins have been shown both in vivo and in vitro to have ubiquitin E3 ligase activity. (embl.de)
  • A role for the ubiquitin ligase Nedd4 in membrane sorting of LAPTM4 proteins. (nih.gov)
  • SHARPIN forms a linear ubiquitin ligase complex regulating NF-B activity and apoptosis. (nature.com)
  • Degradation of CIC protein following lack of ATXN1L was as an alternative noticed to be mediated by the E3 ubiquitin ligase TRIM25 which was additional validated utilizing glioma-derived cell traces and the TCGA breast carcinoma and liver hepatocellular carcinoma cohorts. (ataxin.com)
  • The p53 interacting partner protein NUMB (homology of numb protein) preserves this intrinsic cellular asymmetry by preventing ubiquitin-mediated proteolysis of p53 catalyzed by the MDM2 E3 ubiquitin ligase 11 . (nature.com)
  • For many proteins ubiquitin is critical for controlling the degradation of receptors, but it is unknown what proteins are responsible for controlling this (e.g. the nature of the ubiquitin ligase) The images show a clear requirement for receptor (green) to be ubiquitinated or it remains on the endosome limiting membrane. (abdn.ac.uk)
  • In this context, during any sort of stress condition the alternative reading frame protein p14ARF subtracts MDM2, an E3 ubiquitin ligase, from the interaction with p53 in manner to free and stabilise p53 level in the nucleolus of the cell where it inhibits RNA polymerase I activity [ 3 ]. (biomedcentral.com)
Pathways18
  • Monoubiquitination has been linked to membrane protein endocytosis pathways. (wikipedia.org)
  • His group characterised many of the SNARE proteins that catalyse vesicle fusion, including the sorting signals that ensure their correct location, and the transport pathways and coat proteins that mediate this. (cam.ac.uk)
  • Specifically we evaluate the effect of increased dietary protein intake and caloric restricted diets on gene expression in skeletal muscle, particularly focusing on biosynthesis, degradation and the expression of genes in the ubiquitin-proteosome (UPP) and mTOR signaling pathways, including MuRF-1, MAFbx/atrogin-1, mTORC1, and S6K1. (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)
  • We discuss cross-talk of the MAPK/ERK signaling pathway with other signaling pathways, in particular interplay with the Hippo/MST pathway. (mdpi.com)
  • Here, we present a mathematical model of receptor sorting into alternative pathways that explains the EGF-concentration dependent response of CIE. (biomedcentral.com)
  • Recent studies on the involvement of the G12 family of heterotrimeric G proteins (Gα12 and Gα13, the products of the GNA12 and GNA13 genes, respectively) in oncogenic pathways have uncovered a link between G12. (biomedcentral.com)
  • Much of the signalling involved in DDR pathways relies on post-translational modification of cellular proteins to trigger changes in their behaviour. (lancaster.ac.uk)
  • Protein phosphorylation events play a key role within many DDR pathways and have been the subject of intense study. (lancaster.ac.uk)
  • Other ongoing research is in the area of cell death, particularly apoptosis, where there is activation of proteolytic pathways (mainly the caspase cascade) that mediate degradation of cellular proteins. (cost-proteostasis.eu)
  • Our research bridges a conceptual gap between mitochondria activity, signaling pathways, and metabolic networks conserved from yeast to humans. (cost-proteostasis.eu)
  • Proteins targeted to the peroxisome (in plants called glyoxisomes) are synthesized in the cytoplasm of the cell and are targeted to the peroxisome post-translationally, possibly via multiple pathways. (tcdb.org)
  • Despite the wealth of information available, it is still unclear exactly how p38 MAPK signaling pathways are regulated by many GPCRs, with current p38 targeted therapies having failed to meet clinical needs. (uga.edu)
  • GPCRs and MAPK-dependent signaling pathways regulate many physiological and pathophysiological processes and are the principle targets of more than 50% of current therapeutics. (uga.edu)
  • Insulin receptor substrates (IRSs) are major targets of IGF-I receptor (IGF-IR) tyrosine kinase activated by IGFs, and are known to play important roles in the activation of downstream signaling pathways, such as the Erk1/2 pathway. (oncotarget.com)
  • Tumor suppressors, oncogenes and alternatively deregulated upstream signalling pathways can directly influence the RNA polymerase I activity inducing hyper activation of rRNA transcription in cancer cells. (biomedcentral.com)
  • Nucleolar activity is also influenced by the interaction between pathways activated from extracellular signals in order to coordinate ribosome synthesis and cell proliferation [ 6 ]. (biomedcentral.com)
  • Generally, these receptors explain their function on the cell membrane where, after the binding with growth factors or neuregulin undergo to homo or hetero oligomerization with the activation of the intrinsic tyrosine kinase activity and the subsequent recruitment of proteins involved in the cytoplasmic signalling pathways. (biomedcentral.com)
Ligases14
Receptors20
  • Vacuolar protein sorting 23A (VPS23A), a key component of the endosomal sorting complex required for transport I, mediates the entry of ubiquitinated ABA receptors into the vacuole for degradation. (phys.org)
  • It inactivates the receptors that respond to the signal, or the transporter molecules that suck up the signal chemical by removing them from the cell surface. (alzforum.org)
  • This is the fate of proteins whose degradation is regulated - such as activated signalling receptors, or excess transporters and channels. (cam.ac.uk)
  • here, discrete export signals on the cargo are recognized and captured by specific receptors that are concentrated at sites of vesicle budding. (biologists.com)
  • This process depends on the general physico-chemical features of the cargo membrane protein and on the interactions of these features with the collective properties of the bilayer, instead of the one-to-one intermolecular interactions that exist between discrete signals and their receptors. (biologists.com)
  • Interestingly, cadherin-11 has no known intrinsic signaling activity and is thought to affect cell behavior via interactions with other cell surface receptors. (bvsalud.org)
  • These interactions between cadherin-11 and PDGFRs indicate a crosstalk between these receptors and their downstream signaling activities but the nature of this crosstalk is not entirely known. (bvsalud.org)
  • Protein phosphorylation of G-protein-coupled receptors (GPCR) is central to the myriad of functions that these ubiquitous receptors perform in biology. (biomedcentral.com)
  • The ESCRT-0 complex binds ubiquitin and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes (By similarity). (nih.gov)
  • The protein encoded by this gene is closely related to STAM, an adaptor protein involved in the downstream signaling of cytokine receptors, both of which contain a SH3 domain and the immunoreceptor tyrosine-based activation motif (ITAM). (nih.gov)
  • Paula studied protein delivery to lysosomes at the Cambridge Institute of Medical Research for her first postdoc, and for her second she investigated the role of ubiquitin in the signalling and down-regulation of growth factor receptors at the Physiological Laboratory, University of Liverpool. (swansea.ac.uk)
  • Two peroxisomal targeting signals, PTS1 and PTS2, are recognized by separate sets of receptors. (tcdb.org)
  • On completion of my PhD, I took a postdoctoral position at the University of California, San Francisco, where I continued my training in the laboratory of Prof Mark von Zastrow, a renowned leader in the field of endocytic trafficking in the function of G-protein-coupled receptors, where I investigated the role of Ubiquitin in endosomal trafficking. (abdn.ac.uk)
  • My research involves investigating the mechanisms by which G-protein-coupled Receptors are regulated to maintain signalling and homeostasis. (abdn.ac.uk)
  • G-protein coupled receptors (GPCRs), represent the largest family of cell surface receptors and are the prime regulators of many physiological systems. (abdn.ac.uk)
  • Too few receptors and the signal is missed, too many and the signal overwhelms the cell. (abdn.ac.uk)
  • This signalling fidelity of GPCRs is maintained by an elegant series of interactions that firstly prevent signalling and is followed by a regulated trafficking process involving the removal of desensitised receptors from the surface of the cell (internalisation) followed by either recycling to the plasma membrane for repeated signalling (resensitisation) or targeting to the lysosome for destruction and downregulation (Figure 1). (abdn.ac.uk)
  • My specific interests lie in how the levels of receptor are maintained or downregulated in the extended presence of agonist, and what mechanisms determine how receptors are sorted to the lysosome, in particular determining the distinct processes that control different receptor types. (abdn.ac.uk)
  • Since the EGFR signalling promotes proliferation in tumor the EGFR receptors often represent a marker of resistance with poor prognosis. (biomedcentral.com)
  • 2004) and subsequently to report on selective Aβ dependent alterations in synaptic proteins and neurotransmitter receptors, including surface glutamate receptors and PSD-95 (Almeida et al. (lu.se)
Degradation10
  • For example, a common 4-ubiquitin tag, linked through the lysine at position 48 (K48) recruits the tagged protein to the proteasome, and subsequent degradation. (wikipedia.org)
  • In recent years, studies have found that ubiquitination mediated protein degradation plays an important role in regulating the ABA signaling pathway. (phys.org)
  • Both the EGFR and the DAT proteins have sites to which the molecule ubiquitin-best known as labeling a protein for degradation-can attach. (alzforum.org)
  • These proteins are marked for degradation by addition of the small protein ubiquitin to their cytoplasmic domains, the attached tag acting as a sorting signal for the multivesicular body pathway. (cam.ac.uk)
  • USP8 deubiquitinates EPS15 and regulates EGFR degradation and MAPK signaling via removing conjugated ubiquitin from EGFR (1). (signalchem.com)
  • Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation. (nature.com)
  • The MIT Domain of UBPY Constitutes a CHMP Binding and Endosomal Localization Signal Required for Efficient Epidermal Growth Factor Receptor Degradation. (swansea.ac.uk)
  • Useful in vitro research using ATXN1L human cell traces revealed that lack of ATXN1L results in the buildup of polyubiquitinated CIC protein, selling its degradation by means of the proteasome. (ataxin.com)
  • Cell-fate-determinant molecule NUMB-interacting protein (TBC1D15) is overexpressed and contributes to p53 degradation in TICs. (nature.com)
  • Here we find that in Caenorhabditis elegans, mouse, rat and human neurons, dendritically and axonally polarized transmembrane proteins are recognized by endocytic machinery in the AIS, robustly endocytosed and targeted to late endosomes for degradation. (stanford.edu)
Pathway18
  • Misfolded proteins are frequently degraded in the endoplasmic reticulum, but once proteins leave the ER the main route to destruction is via the multivesicular body pathway to lysosomes or vacuoles. (cam.ac.uk)
  • In this Commentary, I review evidence in favor of the idea that partitioning of TMDs into bilayer domains that are endowed with distinct physico-chemical properties plays a pivotal role in the transport of membrane proteins within the early secretory pathway. (biologists.com)
  • The combination of such self-organizational phenomena with canonical intermolecular interactions is most likely to control the release of membrane proteins from the ER into the secretory pathway. (biologists.com)
  • March11 appears to have a role in ubiquitin-mediated protein sorting in the trans-Golgi network (TGN)-multivesicular body (MVB) transport pathway (Morokuma et al. (utsouthwestern.edu)
  • 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)
  • Targeted inhibition of individual kinases of the MAPK signaling pathway using synthetic compounds represents a promising way to effective anti-cancer therapy. (mdpi.com)
  • Using the Drosophila nephrocyte as a genetic screen platform, most genes involved in endocytosis and cell trafficking were screened, and the key components were identified of the cell trafficking pathway required for SD protein endocytosis and recycling. (sdbonline.org)
  • The SD protein endocytosis and recycling pathway was found to contain clathrin , dynamin , AP-2 complex, like-AP180 (Lap) , auxilin and Hsc70-4 (the endocytosis part) followed by Rab11 and the exocyst complex (the recycling part). (sdbonline.org)
  • Disrupting any component in this pathway led to disrupted SD on the cell surface and intracellular accumulation of mislocalized SD proteins. (sdbonline.org)
  • This study provides the first in vivo evidence of trapped SD proteins in clathrin-coated pits at the plasma membrane when this pathway is disrupted. (sdbonline.org)
  • All genes in this SD protein endocytosis and recycling pathway, as well as SD proteins themselves, are highly conserved from flies to humans. (sdbonline.org)
  • Thus, these results suggest that the SD proteins in human kidney undergo the same endocytosis and recycling pathway to maintain the filtration structure, and mutations in any genes in this pathway could lead to abnormal SD and renal diseases. (sdbonline.org)
  • Though transcriptomic signatures of ATXN1L KO cell traces indicated upregulation of the mitogen-activated protein kinase pathway, ERK exercise was discovered to contribute to CIC operate however not stability. (ataxin.com)
  • Speciality: I have established the Nematode C. elegans as a genetic and proteomic platform to study the regulation of the mevalonate pathway that is critical for cholesterol biosynthesis as well as for the synthesis of metabolites required for small GTPase protein activation and cellular respiration. (cost-proteostasis.eu)
  • By placing ubiquitin and sumo as key regulators of HMGCS1 protein, our findings uncover a new link between post-translation modification and mevalonate pathway regulation. (cost-proteostasis.eu)
  • The p38 mitogen-activated protein kinase (MAPK) pathway is a key mediator of vascular inflammatory responses in lung disease and is an important drug target for the treatment of chronic obstructive pulmonary disease (COPD) and cancer. (uga.edu)
  • We provided evidence for Aβ-dependent dysfunction in the ubiquitin proteasome system and multivesicular body (MVB) sorting pathway (Almeida et al. (lu.se)
  • In addition, we provided insights into Aβ modulation of the mTOR pathway, a central signaling pathway that is implicated in aging, synaptic plasticity and autophagy (Ma et al. (lu.se)
Receptor13
  • There is also traffic in the opposite direction: molecules are transported into the cell from outside, including worn-out or excess receptor and channel proteins from the outside of the cell membrane. (alzforum.org)
  • Our main result is that a scenario where different endocytosis routes consume the same form of receptor corroborates the observation of a clear-cut, stimulus dependent sorting. (biomedcentral.com)
  • Ligand induced phosphorylation of EGF receptor creates docking sites for adaptor proteins, such as EPS15, epsin and AP-2 [ 6 , 7 ]. (biomedcentral.com)
  • Via direct or indirect binding, adaptors recruit the receptor to special membrane regions which are characterized by a particular composition of cage-proteins and/or -lipids [ 8 , 9 ]. (biomedcentral.com)
  • In this study, we used a computational model to represent the experimentally proven interactions between cadherin-11 and the two PDGFRs and we inspected whether the crosstalk also exists downstream of the signaling initiated by the two receptor families. (bvsalud.org)
  • G protein-coupled receptor kinase 2 (GRK2) was originally identified as the kinase that mediates. (biomedcentral.com)
  • The Ubiquitin Isopeptidase UBPY Regulates Endosomal Ubiquitin Dynamics and Is Essential for Receptor Down-regulation. (swansea.ac.uk)
  • In the budding yeast Saccharomyces cerevisiae , the minimal transport machinery includes the membrane proteins Pex13 and Pex14 and the cargo-protein-binding transport receptor, Pex5. (tcdb.org)
  • AAA peroxins are involved in the export from peroxisomes of Pex5p, the PTS1 (peroxisome-targeting signal type 1) receptor. (tcdb.org)
  • The Grimsey lab focuses on the impact of G protein-coupled receptor (GPCR) mediated non-canonical p38 Mitogen Activated Protein (MAP) kinase signaling in vascular inflammation, angiogenesis and chronic lung disease. (uga.edu)
  • Dores MR, Grimsey NJ , Mendez F and Trejo J. (2016) ALIX Regulates the Ubiquitin Independent Lysosomal Sorting of the P2Y1 Purinergic Receptor via a YPXL Motif. (uga.edu)
  • Grimsey NJ , Coronel LJ, Cordova IC, and Trejo J. (2016) Recycling and Endosomal Sorting of Protease-Activated Receptor-1 Is Distinctly Regulated by Rab11A and Rab11B Proteins. (uga.edu)
  • Dores MR, Lin H, Grimsey NJ , Mendez F and Trejo J. (2015) The -Arrestin ARRDC3 Mediates ALIX Ubiquitination and G Protein-Coupled Receptor Lysosomal Sorting. (uga.edu)
Mitogen-activa2
  • p38 mitogen-activated protein kinase has been implicated in both skeletal muscle atrophy and hypertrophy. (biomedcentral.com)
  • Aberrations in Capicua (CIC) have lately been implicated as a adverse prognostic consider a mess of most cancers sorts by means of the derepression of targets downstream of the mitogen-activated protein kinase (MAPK) signaling cascade, similar to oncogenic E26 transformation-specific (ETS) transcription components. (ataxin.com)
Ubiquitination8
Homeostasis4
  • This enables cells to communicate and respond to external environments, maintain cellular homeostasis, and transduce signals. (mdpi.com)
  • aux depletion leads to excessive ISC proliferation and midgut homeostasis disruption, which is unlikely caused by defective Notch signaling. (sdbonline.org)
  • Immunoreceptor signaling during development, homeostasis, and effector function of T cells and NK cells. (upstate.edu)
  • Role of SUMO and ubiquitin signaling in adult tissue homeostasis focusing on adult gut, innate immunity. (cost-proteostasis.eu)
Regulates2
  • The GTPase Rab11 regulates endosomal protein trafficking and previous work has shown that loss of Rab11 caused intestinal inflammation and hyperplasia in mice and flies. (sdbonline.org)
  • Our group is interested in protein SUMOylation, a post-translational modification that predominantly regulates nuclear processes including transcription and the DNA damage response. (cost-proteostasis.eu)
Regulation7
  • Subsequent genetic experiments demonstrated that UBP12 and UBP13 can participate in the regulation of ABA signaling and plant responses to drought stress through VPS23A. (phys.org)
  • At the Ipsen Foundation's 23rd Colloquium on Alzheimer's Disease, held 28 April 2008 in Paris, the focus shifted from the rogue proteins that characterize these diseases to the regulation of their movements around the cell. (alzforum.org)
  • Cross-talk between plant cells and their surroundings requires tight regulation of information exchange at the plasma membrane (PM), which involves dynamic adjustments of PM protein localization and turnover to modulate signal perception and solute transport at the interface between cells and their surroundings. (cas.cz)
  • The course is focused on principles and mechanisms of gene expression regulation in both prokaryotic and eukaryotic cells, including regulation of transcription, translation and protein stability. (cuni.cz)
  • USP8 (ubiquitin carboxyl-terminal hydrolase 8) is a member of the ubiquitin-specific processing protease family of proteins and is involved in the regulation of endosomal ubiquitin processes for endosome morphology, cargo sorting and membrane trafficking at the early endosome stage. (signalchem.com)
  • Elucidate the structure, dynamics and functions of intrinsically disordered proteins and protein regions (IDPs/IDRs) and their biological regulation by Post-translational modifications. (upstate.edu)
  • Molecular mechanisms responsible for signaling and regulation of plant response to nutrient deficiency stress and other abiotic stresses (with focus on the role of posttranslational processes). (cost-proteostasis.eu)
EGFR5
  • C-Cbl monoubiquitylates EGFR, signaling for its internalization and trafficking to the lysosome. (wikipedia.org)
  • However, the EGFR can undergo endocytosis when no ubiquitin is attached, using a complex of specific helper molecules, whereas DAT requires the attachment of ubiquitin to activate a specific enzyme that triggers endocytosis ( Miranda and Sorkin, 2007 ). (alzforum.org)
  • This study found that auxilin (Aux) restricts intestinal stem cell (ISC) proliferation mainly through EGFR signaling. (sdbonline.org)
  • Interestingly, aux depletion causes a dramatic increase in EGFR signaling, with a strong accumulation of EGFR at the plasma membrane and an increased expression of EGFR ligands in response to tissue stress. (sdbonline.org)
  • Finally, blocking EGFR signaling completely suppresses the defects caused by aux depletion. (sdbonline.org)
Kinase2
  • NM23-H1 (also known as NME1) was the first identified metastasis suppressor, which displays a nucleoside diphosphate kinase (NDPK) and histidine protein kinase activity. (biomedcentral.com)
  • Grimsey NJ, Aguilar, B, Smith TH, Le P, Soohoo AL, Puthenveedu MA, Nizet V and Trejo J. (2015) Ubiquitin Plays an Atypical Role in GPCR-Induced p38 MAP Kinase Activation on Endosomes. (uga.edu)
Endocytosis6
  • Endocytosis is one way of limiting the responses of a cell to signals coming from outside. (alzforum.org)
  • Unlike membrane remodeling in classical curvature-dependent processes like clathrin-mediated endocytosis, cristae junctions are most likely shaped by integral membrane proteins. (db-engine.de)
  • In animals and fungi, turnover of PM proteins is controlled by reversible ubiquitylation, which signals endocytosis and delivery to the cell's lytic compartment, and there is emerging evidence for related mechanisms in plants. (cas.cz)
  • We demonstrate that ubiquitin acts as a principal signal for PM protein endocytosis in plants and reveal dynamic adjustments in PIN2 ubiquitylation coinciding with variations in vacuolar targeting and proteolytic turnover. (cas.cz)
  • SD proteins are known to undergo endocytosis and recycling to maintain the integrity of the filtration structure. (sdbonline.org)
  • Following endocytosis GPCRs can undergo recycling to the plasma membrane (1) (possibly regulated by the retromer) or sorting to the lysosome. (abdn.ac.uk)
Adaptor1
  • The coat on the budding vesicle comprises two layers, an inner layer of adaptor proteins (gray ovals) and an outer layer that forms a polyhedral cage. (biologists.com)
Proteasome2
  • Commonly, E3s polyubiquitinate their substrate with Lys48-linked chains of ubiquitin, targeting the substrate for destruction by the proteasome. (wikipedia.org)
  • Finley, D. Recognition and processing of ubiquitin-protein conjugates by the proteasome. (nature.com)
Synaptic proteins1
  • SMOC1 and SPON1 proteins associated with Aß plaques were elevated in AD CSF nearly 30 years before the onset of symptoms, followed by changes in synaptic proteins, metabolic proteins, axonal proteins, inflammatory proteins and finally decreases in neurosecretory proteins. (cdc.gov)
Intracellular4
  • To ensure that the correct sets of molecules talk to each other, the intracellular space is highly structured and special signals are employed to move specific molecules from one structure to another. (alzforum.org)
  • These enzymes add ubiquitin (see MIM 191339) to target lysines in substrate proteins, thereby signaling their intracellular transport. (utsouthwestern.edu)
  • Involved in intracellular signal transduction mediated by cytokines and growth factors. (nih.gov)
  • TAR DNA-binding protein of 43 kDa (TDP-43) is a serious element of intracellular aggregates fashioned in brains of the sufferers with frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), that are correctively known as TDP-43 proteinopathies. (ataxin.com)
MAPK1
  • Deregulation of the MAPK signaling occurs under many pathological conditions including neurodegenerative disorders, metabolic syndromes and cancers. (mdpi.com)
Endoplasmic reticulum2
Cytoplasmic1
  • Loss of Pcs impairs Rab11 localization on the trans-side of Golgi units and induces the cytoplasmic accumulation of post-Golgi vesicles bearing rhabdomere proteins, as observed in Rab11-deficiency. (sdbonline.org)
Mechanisms5
  • The aim of this unit is to examine the molecular mechanisms of protein sorting in eukaryotes, and will review recent data demonstrating that some of these processes are fundamental to all living cells. (manchester.ac.uk)
  • These painstaking methods are now being applied to investigating how molecules are moved around in neurons and how the proteins that characterize neurodegenerative diseases may disrupt one or more of these mechanisms. (alzforum.org)
  • There are a number of plausible mechanisms, several of them mediated by dietary protein that may provide some explanation for the negative net protein balance. (biomedcentral.com)
  • The molecular mechanisms of other cellular processes like protein sorting and distribution, membrane transport, cytoskelet function and basic processes of cell signalling are also emphasised. (cuni.cz)
  • As CIC standing has develop into a prognostic consider a number of most cancers sorts, additional data into the mechanisms which govern CIC stability and performance could show helpful for future therapeutic approaches. (ataxin.com)
Yeast2
  • This was the starting point for wider studies, mostly in yeast, of protein sorting and trafficking. (cam.ac.uk)
  • Vacuolar H+-ATPase dysfunction rescues intralumenal vesicle cargo sorting in yeast lacking PI(3,5)P2 or Doa4. (colorado.edu)
Vesicle1
Processes3
  • Soluble cargo can be recruited to ER exit sites by signal-mediated processes (cargo capture) or by bulk flow. (biologists.com)
  • In this protocol, we describe how unique properties of ubiquitin (Ub)-binding domains (UBDs) can be used to selectively detect, visualize and inhibit Ub-dependent processes in mammalian cells. (nature.com)
  • 2011 ) have reviewed the processes by which matrix and membrane proteins are incorporated into the peroxysome. (tcdb.org)
Specificity2
Membrane proteins3
  • Eukaryotic cells are subdivided into membrane-bounded organelles, each with a characteristic set of membrane proteins. (cam.ac.uk)
  • For membrane proteins, a third mechanism, based on the interaction of their transmembrane domain (TMD) with lipid microdomains, must also be considered. (biologists.com)
  • Most peroxisomal membrane proteins do not have PTS1 or PTS2, and insertion requires several peroxins distinct from those required for import of soluble matrix proteins. (tcdb.org)
Mass spectrometry2
Molecule2
  • A protein can be tagged with a single ubiquitin molecule (monoubiquitylation), or variety of different chains of ubiquitin molecules (polyubiquitylation). (wikipedia.org)
  • Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. (embl.de)
Extracellular2
  • The ability of a cell to respond to extracellular signals such as neurotransmitters is vital for regulating normal physiological function. (abdn.ac.uk)
  • We found 32 dementia-associated plasma proteins that were involved in proteostasis, immunity, synaptic function, and extracellular matrix organization. (cdc.gov)
Endosomal Sorting1
  • USP8, a Regulator of Endosomal Sorting, Is Involved in Mouse Acrosome Biogenesis Through Interaction with the Spermatid ESCRT-0 Complex and Microtubules, Biology of Reproduction, 82(5), 930-939, 2010. (signalchem.com)
Tumor3
  • We describe how these moieties can be used to inhibit tumor necrosis factor (TNF)-mediated NF-κB signaling and to detect ubiquitinated cytosolic Salmonella in living cells, emphasizing a more flexible use compared with chain-specific antibodies. (nature.com)
  • Dysregulation of IGF signaling represents a central tumor promoting principle in human carcinogenesis. (oncotarget.com)
  • GEP analyses were performed on highly purified, flow-cytometry sorted tumor-cells from eight subgroups of BCLs. (lu.se)
Role6
  • Some studies have suggested a role for this protein in maintaining centriole-nucleated sensory organelles termed primary cilia, and AS is now considered to belong to the growing class of human genetic disorders linked to ciliary dysfunction (ciliopathies). (springer.com)
  • The legume-rhizobium symbiosis offers an excellent model system to study the role of Ca 2+ signaling in eukaryotic cell development. (elifesciences.org)
  • My research interests are in understanding how cells maintain genome integrity and, in particular, in understanding the role played by ubiquitin and SUMO modification in this process. (lancaster.ac.uk)
  • Sorting Nexin 16:Structure,Function,and Role in Diseases]. (nih.gov)
  • Upon IL-2 and GM-CSL stimulation, it plays a role in signaling leading to DNA synthesis and MYC induction. (nih.gov)
  • Benjamin Foster is a postdoctoral research associate investigating the role of ubiquitin and ubiquitin-like signalling in genome stability. (portlandpress.com)
Protease1
  • To explore this question, researchers from XIE Qi's team at the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences found deubiquitinases ubiquitin-specific protease 12 (UBP12) and UBP13 are the interacting proteins of VPS23A via performing a screening assay. (phys.org)
Vacuolar1
  • Moreover, we provide experimental evidence indicating that PIN2 vacuolar sorting depends on modification specifically by lysine63-linked ubiquitin chains. (cas.cz)
Transmembrane2
  • Orthologous to human LAPTM4B (lysosomal protein transmembrane 4 beta). (nih.gov)
  • A large pore is formed by transmembrane proteins. (tcdb.org)
Axonal2
  • Neurons are highly polarized cells with extensive axonal and dendritic projections that send and receive signals over long distances. (stanford.edu)
  • Neuronal polarity requires sorting and maintaining a unique set of proteins to the neuron's distinct axonal and somatodendritic domains. (stanford.edu)
Stability3
  • A series of biochemical experiments demonstrated that UBP12 and UBP13 can deubiquitinate VPS23A and maintain the protein stability of VPS23A. (phys.org)
  • The Ataxin -family protein ATXN1L has beforehand been reported to work together with CIC in each developmental and illness contexts to facilitate the repression of CIC goal genes and promote the post-translational stability of CIC. (ataxin.com)
  • Funded by a Wellcome Trust Ph.D studentship, her current research focuses on understanding how ubiquitylation governs the stability and sorting of a remarkably short-lived immune checkpoint protein, CTLA4. (portlandpress.com)
Mechanism4
  • However, the precise mechanism by which a high protein diet may mitigate dietary weight loss induced reductions in fat free mass has not been fully elucidated. (biomedcentral.com)
  • The precise mechanism by which an increased dietary protein intake may mitigate weight loss induced reductions in FFM has not been fully elucidated. (biomedcentral.com)
  • In the past years, it has emerged as a powerful mechanism for the cell to temporally and spatially control its signaling response [ 5 ]. (biomedcentral.com)
  • Our studies have revealed a novel mechanism for GPCR dependent activation of non-canonical p38 signaling. (uga.edu)
Mitochondria2
  • Sorting of proteins to specific compartments within mitochondria. (manchester.ac.uk)
  • We further characterized this circuit and found how it is regulated temporally by an age-dependent cytosol-to-mitochondria sorting of specific circuit components. (cost-proteostasis.eu)
Deubiquitinase1
  • Here we identified the deubiquitinase, ubiquitin specific peptidase 9X (USP9X) as a novel binding partner of IRS-2. (oncotarget.com)
MTOR1
  • Maintenance of fat free mass is dependent upon nutrient stimulation of protein synthesis via the mTOR complex, although during caloric restriction a decrease (atrophy) in skeletal muscle may be driven by a homeostatic shift favouring protein catabolism. (biomedcentral.com)
Morphology1
  • Dendrites require exact and well timed supply of protein substrates to distal areas to make sure the proper morphology and performance of neurons. (ataxin.com)
Physiological1
  • They are essential regulators of cyclic nucleotide signaling with diverse physiological functions. (axonmedchem.com)
Peptides2
  • Water 2H and 17O spin relaxation is used to study water dynamics in the hydration layers of two small peptides, two globular proteins and in living cells of two microorganisms. (lu.se)
  • This distribution comprises a small fraction of protein-specific hydration sites, where water rotation is strongly retarded, and a dominant fraction of generic hydration sites, where water rotation is as fast as in the hydration shells of small peptides. (lu.se)
Mitochondrial3
  • Mitochondrial targeting signals. (manchester.ac.uk)
  • At least some of these proteins are likely to be found within the MICOS complex (mitochondrial contact site and cristae organizing system). (db-engine.de)
  • Mitochondrial biology, stress signaling and aging-related degenerative diseases. (upstate.edu)
Downstream2
  • Overall, our predictions suggest the existence of another layer of crosstalk, namely between ß-catenin (downstream to cadherin-11) and an ERK inhibitor protein (e.g. (bvsalud.org)
  • Similar to STAM, this protein acts downstream of JAK kinases, and is phosphorylated in response to cytokine stimulation. (nih.gov)
Ubiquitylation2
  • The final step in the first ubiquitylation event is an attack from the target protein lysine amine group, which will remove the cysteine, and form a stable isopeptide bond. (wikipedia.org)
  • Here, we describe the fate of Arabidopsis PIN2 protein, required for directional cellular efflux of the phytohormone auxin, and identify cis- and trans-acting mediators of PIN2 ubiquitylation. (cas.cz)
Viral proteins1
  • The RING-variant domain is a C4HC3 zinc-finger like motif found in a number of cellular and viral proteins. (embl.de)
Genes1
  • Over two dozen proteins involved in protein import and membrane insertion, peroxins, encoded by PEX genes, have been characterized. (tcdb.org)
Endosome1
  • The protein encoded by this gene associates with late endosome membranes as is involved in tubule formation, cholesterol transport, and transport of tetraspanin CD81. (nih.gov)
Membranes2
  • To create particular shaped cells and cell organelles, membranes must undergo deformations which are determined by the structure and elasticity of the membrane and this process is most probable driven by proteins, lipids and/or interplay of both. (db-engine.de)
  • These proteins act as channels and allow ions to move across cell membranes. (elifesciences.org)
Compartments1
  • As in a petrochemical plant, different steps in the production process take place in dedicated compartments, and signaling systems regulate the movement of molecules between compartments. (alzforum.org)
GPCR1
  • Figure 1 - Simplified model of GPCR post-endocytic sorting. (abdn.ac.uk)
Gene5
  • Recruitment of the linear ubiquitin chain assembly complex stabilizes the TNF-R1 signaling complex and is required for TNF-mediated gene induction. (nature.com)
  • This gene encodes a member of the sorting nexin family. (nih.gov)
  • Description of the protein which includes the UniProt Function and the NCBI Gene Summary. (nih.gov)
  • In contrast, loss-of-function mutations in the let-7 microRNA gene prevent a developmental decline in dendritic growth ability, whereas loss-of-function mutations in its direct target, the lin-41 tripartite motif protein gene, cause further decline. (stanford.edu)
  • The LIN-14 transcription factor likely directly represses dma-1 gene expression through a transcriptional means, whereas the LIN-41 tripartite motif protein likely indirectly promotes dma-1 gene expression through a posttranscriptional means. (stanford.edu)
Modification2
  • Ubiquitin and SUMO modification of specific proteins is recognised as an important element of the cellular response to genetic damage. (lancaster.ac.uk)
  • Through a combination of biochemical analysis, using purified proteins and cell-free extracts of Xenopus laevis eggs, and in vivo cell biological analysis using established human cell lines, my group is identifying key targets of ubiquitin and SUMO modification in the DNA damage response. (lancaster.ac.uk)
Responses2
  • protective cytotoxic t-cell responses induced by venezuelan equine encephalitis virus replicons expressing ebola virus proteins. (liverpool.ac.uk)
  • Speciality: Previous and ongoing research in my group is in the area of stress responses, including the unfolded protein response and heat shock responses. (cost-proteostasis.eu)
Skeletal3
  • During eucaloric conditions the continual breakdown of protein that occurs in the body's organs and vital tissues is replenished in the post-absorptive state via supply of amino acids derived primarily from the skeletal muscle component of FFM[ 7 ]. (biomedcentral.com)
  • Providing there is adequate dietary protein intake, muscle protein gains which occur in the fed state balances the loss of muscle protein which occurs in the post absorptive state allowing day to day skeletal muscle mass to remain relatively constant[ 7 , 10 ]. (biomedcentral.com)
  • The FFM reduction that typically occurs during CR weight loss also implies a negative net skeletal muscle protein balance. (biomedcentral.com)
Mutation1
Tissues1
  • To test the idea that loss of Rab11 may promote cancer progression, archival human patient tissues were analyzed and 51 out of 70 colon cancer tissues had lower Rab11 protein staining. (sdbonline.org)
Lipid3
  • Each cell produces thousands of different protein and lipid molecules. (alzforum.org)
  • Specifically, we use recombinantly expressed proteins and purified native protein complexes in combination with a wide variety of model membrane systems, including planar lipid bilayers (single channel electrophysiology), giant unilamellar vesicles, lipid nanodiscs and supported bilayers. (db-engine.de)
  • Protein-lipid interactions. (cost-proteostasis.eu)