• SCF ubiquitin ligases in the maintenance of genome stability. (nih.gov)
  • Among these mechanisms, ubiquitin-mediated degradation of key proteins has an important role in the regulation of the DDR, centrosome duplication and chromosome segregation. (nih.gov)
  • This review discusses the functions of a group of ubiquitin ligases, the SCF (SKP1-CUL1-F-box protein) family, in the maintenance of genome stability. (nih.gov)
  • Given that general proteasome inhibitors are currently used as anticancer agents, a better understanding of the ubiquitylation of specific targets by specific ubiquitin ligases may result in improved cancer therapeutics. (nih.gov)
  • An SCF-like ubiquitin ligase complex that controls presynaptic differentiation. (nih.gov)
  • Many F-box proteins are target recognition subunits of SCF (Skp, Cullin, F-box) ubiquitin-ligase complexes. (nih.gov)
  • The SCF (SKP1/CUL1/F-box protein) complexes are assembled using a CUL1 scaffold. (nih.gov)
  • Substrates are recruited to the complex by SKP1 and a variable F-box protein that determines substrate specificity. (nih.gov)
  • FSN-1 physically associates with RPM-1 and the C. elegans homologues of SKP1 and Cullin to form a new type of SCF complex at presynaptic periactive zones. (nih.gov)
  • The effects of diaphragmatic contractions with assisted mechanical ventilation on diaphragmatic isometric, isotonic contractile properties, or the expression of muscle atrophy factor-box (MAF-box), the gene responsible for muscle atrophy, are unknown. (nih.gov)
  • MAF-box gene was overexpressed with controlled ventilation. (nih.gov)
  • We conclude that preserving diaphragmatic contractions during mechanical ventilation attenuates the force loss induced by complete inactivity and maintains MAF-box gene expression in control. (nih.gov)
  • fsn-1 functions in the same pathway as rpm-1, a gene encoding a large protein with RING finger domains. (nih.gov)
  • The SCF (SKP1/CUL1/F-box protein) complexes are assembled using a CUL1 scaffold. (nih.gov)
  • Many key activators and inhibitors of cell division are targeted for degradation by a recently described family of E3 ubiquitin protein ligases termed Skp1-Cdc53-F-box protein (SCF) complexes. (nih.gov)
  • SCF complexes physically link substrate proteins to the E2 ubiquitin-conjugating enzyme Cdc34, which catalyses substrate ubiquitination, leading to subsequent degradation by the 26S proteasome. (nih.gov)
  • SCF complexes contain a variable subunit called an F-box protein that confers substrate specificity on an invariant core complex composed of the subunits Cdc34, Skp1 and Cdc53. (nih.gov)
  • Through mass spectrometric analysis of Cdc53 associated proteins, we have identified three novel F-box proteins that appear to participate in SCF-like complexes. (nih.gov)
  • Many F-box proteins are target recognition subunits of SCF (Skp, Cullin, F-box) ubiquitin-ligase complexes. (nih.gov)
  • The mammalian PER and CRY proteins form multimeric complexes that enter the nucleus and repress the transcriptional activity of CLK/BMAL1, modulating circadian output (reviewed in references 29 and 41 ). (asm.org)
  • Aurora B complexes with three other proteins, Survivin, Borealin and INCENP. (wikipedia.org)
  • It is accepted that in plants, CDK/cyc complexes phosphorylate the retinoblastoma-related protein (RBR), causing the activation of a set of genes that are regulated by the E2F/DP transcription factor and are necessary for S-phase entry and DNA replication. (plantcell.org)
  • CDK/cycD complexes act at the G1/S checkpoint by phosphorylating the RBR protein, causing the release of the E2F transcription factor and entry into S-phase. (plantcell.org)
  • Complexes that target proteins for degradation often contain F-box proteins. (genetics.org)
  • The association between CUL1 and Skp1, which serves as the molecular scaffold for the components of SCF ubiquitin ligase complexes, was markedly repressed in the presence of HBZ. (asm.org)
  • Although the ubiquitin-proteasome system is necessary for clearance of these repressors, distinct E3 ligase complexes target them: the C-terminal to Lis1 Homology (CTLH) complex targets Cup, TRAL, and ME31B for degradation early in the MZT and the Skp/Cullin/F-box-containing (SCF) complex targets SMG at the end of the MZT. (princeton.edu)
  • SCF (Skp1/Cullin/F-box protein) complexes and anaphase-promoting complexes (APC) represent two major classes of ubiquitin ligases whose activities are thought to regulate primarily the G1/S and metaphase/anaphase cell-cycle transitions, respectively. (elsevier.com)
  • The elongin BC dimer acts as a bridge between pVHL and hCUL-2 because pVHL and hCUL-2 can form distinct complexes with elongins B and C. These results reveal a striking structural resemblance of pVHL/elongin BC/hCUL-2 complex with the E3-like ubiquitin ligase complex SKP1/Cullin/F-box protein with respect to protein composition and sites of interactions. (elsevier.com)
  • The act of ligating UBIQUITINS to PROTEINS to form ubiquitin-protein ligase complexes to label proteins for transport to the PROTEASOME ENDOPEPTIDASE COMPLEX where proteolysis occurs. (harvard.edu)
  • Although some of these networks constitute stable multi-protein complexes while others are more dynamic, they are all built from specific binary interactions between individual proteins. (biomedcentral.com)
  • The APCCdh1 (anaphase promoting complex) and SCFSkp2 (SKP-Cullin-F-box) complexes are E3 ligase activities that modify the corresponding target proteins with ubiquitin in a cell cycle-dependent manner. (mbl.co.jp)
  • The VHL gene product (pVHL) forms a multimeric complex with the elongin B and C, Cul2 and Rbx1 proteins (VCBCR complex), which is homologous to the SCF family of ubiquitin ligase complexes. (ox.ac.uk)
  • The effectors of repression are large multimeric complexes which contain both the repressor proteins that bind to transcription factors and a number of co-repressors that actually mediate transcriptional silencing either by inhibiting the basal transcription machinery or by recruiting chromatin-modifying enzymes. (biomedcentral.com)
  • Both SMRT and N-CoR exist in multi- protein complexes that have an estimated size of 1.5-2 mDa. (biomedcentral.com)
  • Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes. (rush.edu)
  • Nagy Z, Wynne K, von Kriegsheim A, Gambaryan S, Smolenski A. Cyclic Nucleotide-dependent Protein Kinases Target ARHGAP17 and ARHGEF6 Complexes in Platelets. (signagen.com)
  • 2009 ). E3 ligases can function independently as a single component or as part of modular multi-subunit complexes containing a RING module (e.g. (researchsquare.com)
  • Through the F-box, these proteins are linked to the Skp1 protein and the core of SCFs (Skp1-cullin-F-box protein ligase) complexes. (embl.de)
  • The binding of the specific substrates by SCFs complexes is mediated by divergent protein-protein interaction motifs present in F-box proteins, like WD40 repeats, leucine rich repeats [( PUBMED:9529603 ), ( PUBMED:10581972 )] or ANK repeats. (embl.de)
  • Recent work has shown that central to the temporal control mechanism is a relationship between newly identified E3 ubiquitin protein ligases, designated SCFs (Skp1-cullin-F-box protein ligase complexes), which confer substrate specificity on ubiquitination reactions and the activities of protein kinases that phosphorylate substrates destined for destruction at specific sites, thereby converting them into preferred targets for ubiquitin modification catalyzed by SCFs. (embl.de)
  • Ubiquitination of proteins requires a multienzyme system. (nih.gov)
  • A key component of ubiquitination pathways, the ubiquitin ligase, controls both the specificity and timing of substrate ubiquitination. (nih.gov)
  • Murine PER2 (mPER2) hyperphosphorylation induced by the cell-permeable protein phosphatase inhibitor calyculin A is rapidly followed by ubiquitination and degradation by the 26S proteasome. (asm.org)
  • Selective protein degradation mediated by ubiquitination is also directly implicated in TRN development. (genetics.org)
  • S-phase-kinase-interacting protein 2 (Skp2) is identified as an E3 ubiquitin ligase that targets p27 kip1 for ubiquitination and plays a very important role in cell cycle regulation. (arvojournals.org)
  • We previously reported that Skp1, a component of the Skp1-Cullin-F-box protein (SCF) complex essential for the timely degradation of cell cycle proteins by ubiquitination, physically interacts with Bfa1, which is a key negative regulator of the mitotic exit network (MEN) in response to diverse checkpoint-activating stresses in budding yeast. (elsevier.com)
  • These data suggest that mutated SMAD4 proteins undergo rapid degradation in acute myelogenous leukemia cells via SCF β-TrCP1 E3 ligase-mediated protein ubiquitination (or ubiquitylation) and subsequent proteasomal degradation. (elsevier.com)
  • Their rapid turnover by the ubiquitin-proteasome pathway is regulated through phosphorylation of Myc Box I and ubiquitination by the E3 ubiquitin ligase SCFFbxW7 However, N-Myc protein (the product of the MYCN oncogene) is stabilized in neuroblastoma by the protein kinase Aurora-A in a manner that is sensitive to certain Aurora-A-selective inhibitors. (icr.ac.uk)
  • Ubiquitination is the covalent link of target proteins with the small protein ubiquitin and serves as a signal to target protein degradation by the proteasome or to other outcomes such as endocytosis, degradation by the lysosome or specification of cellular localization. (biomedcentral.com)
  • Ubiquitination is the covalent attachment of molecules of the small 76 amino-acids protein ubiquitin to a target protein which is then marked for proteasome destruction or endocytosis or participation in a range of processes. (biomedcentral.com)
  • Ubiquitination along with other post-translational modifications of proteins such as phosphorylation, hydroxylation and acetylation is a regulated process for the execution of which a multitude of regulators exist. (biomedcentral.com)
  • The ubiquitin proteasome system (UPS) regulates the expression levels of cellular proteins by ubiquitination of protein substrates followed by their degradation via the proteasome. (biomedcentral.com)
  • As the PER and CRY proteins are progressively phosphorylated during the night, they are targeted for ubiquitination by specific E3 ligases and are eventually degraded by the proteasome. (hhmi.org)
  • A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. (rush.edu)
  • h) The Ci-3P mutant protein (red), carrying mutations in three PKA phosphorylation sites, is ectopically expressed in CSN4 mosaic wing pouches under the control of ms1096-GAL4. (nih.gov)
  • The mammalian circadian regulatory proteins PER1 and PER2 undergo a daily cycle of accumulation followed by phosphorylation and degradation. (asm.org)
  • CKIε-mediated phosphorylation of PER2 recruits the ubiquitin ligase adapter protein β-TrCP to a specific site, and dominant negative β-TrCP blocks phosphorylation-dependent degradation of mPER2. (asm.org)
  • Localization of Aurora B to the centromere during prometaphase and metaphase requires phosphorylation of the mammalian kinetochore-specific histone-H3 variant centromere protein A (CENP-A). CENP-A associates with the centromere and is necessary for assembly of the kinetochore. (wikipedia.org)
  • This study describes a viral latency mechanism based on phosphorylation-regulated viral replication protein stability that may underlie chronic viral infections for some small genome DNA and RNA viruses. (pnas.org)
  • We show that evolutionarily conserved MCV LT phosphorylation sites are constitutively recognized by cellular Fbw7, βTrCP, and Skp2 Skp-F-box-cullin (SCF) E3 ubiquitin ligases, which degrade and suppress steady-state LT protein levels. (pnas.org)
  • Our data show that phosphorylation of c-Jun caused by overexpression of mitogen-activated protein kinase kinase kinase 1 (Mekk1), an upstream activator of c-Jun, enhances the interaction of c-Jun with WWOX. (aacrjournals.org)
  • Dong Q, Giorgianni F, Beranova-Giorgianni S, Deng X, O'meally RN, Bridges D, Park EA, Cole RN, Elam MB, Raghow R. Glycogen synthase kinase-3 mediated phosphorylation of serine 73 targets sterol response element binding protein-1c (SREBP-1c) for proteasomal degradation. (signagen.com)
  • They bind to other proteins through their armadillo domains and play a variety of roles in the CELL including SIGNAL TRANSDUCTION, regulation of DESMOSOME assembly, and CELL ADHESION. (bireme.br)
  • Here, we review the substrates and pathways regulated by the yeast F-box proteins Cdc4, Grr1 and Met30. (nih.gov)
  • To test whether protection of substrate receptors by deneddylation is a general rule, we first examined the protein stability of Slimb, a substrate receptor for the SCF complex that ubiquitylates several substrates including Ci155 (refs 13, 47). (nih.gov)
  • Genetic studies have identified CKIε (casein kinase Iε) as a key regulator of metazoan circadian rhythm and both genetic and biochemical studies suggest that the PER proteins are important substrates (reviewed in reference 10 ). (asm.org)
  • instead, most mutations are monoallelic missense changes involving specific arginine residues at β-sheet propellor tips that allow the FBXW7 protein to recognise its substrates. (bmj.com)
  • SCF ligases bring ubiquitin conjugating enzymes (either Ubc3 or Ubc4) to substrates that are specifically recruited by the different F-box proteins. (embl.de)
  • In mice, a positively acting heterodimeric transcription factor composed of the PAS-bHLH proteins CLOCK (CLK) and BMAL1 drives transcription of tissue-specific circadian output genes, as well as its own negative regulators, the Period (denoted mPer1 , mPer2 , and mPer3 ), and Cryptochrome ( mCry1 and mCry2 ) genes. (asm.org)
  • Several of these genes encode proteins that contribute to specialized structures required for sensing touch, including large-diameter microtubules, extracellular matrix, and a channel complex that transduces mechanical stimuli into electrical signals. (genetics.org)
  • These circadian rhythms are generated and maintained by the circadian clock, which consists of positive and negative feedback loops formed by a large number of genes and proteins. (elifesciences.org)
  • Since the cryptochromes regulate the activity of BMAL1 and CLOCK, the proteins associated with the two master clock genes, these changes can have a significant effect on the circadian clock of an organism. (elifesciences.org)
  • Brain and muscle ARNT-like protein 1 (BMAL1) and 'circadian locomotor output cycles kaput' (CLOCK) activate expression of many transcripts including the period ( Per1 , Per2 , and Per3 ) and cryptochrome ( Cry1 and Cry2 ) genes, whose protein products (PERs and CRYs) inhibit CLOCK and BMAL1, resulting in rhythmic expression. (elifesciences.org)
  • Analyzing the expression of some factors related to proteolytic and thermogenic processes, we observed in tumor-bearing animals an increased expression of genes involved in proteolysis such as ubiquitin ligases Muscle Ring Finger 1 (MuRF-1) and Muscle Atrophy F-box protein (MAFBx). (lu.se)
  • It is well established that the Tax protein is a potent oncoprotein that either strongly activates or inactivates the transcription of target genes as well as interacts with numerous cellular factors that promote the survival and immortalization of HTLV-1-infected T cells ( 8 - 13 ). (asm.org)
  • An interaction between the two proteins results in activation of reporter genes that have upstream binding sites for the BD. (biomedcentral.com)
  • We assigned 16,169 out of 29,624 FST genes to 34 MapMan classes, including major three categories such as DNA, RNA and protein. (springeropen.com)
  • To determine the functions of the proteins, 38 co-expressed DAPs from the two groups were annotated using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analytical tools. (beds.ac.uk)
  • These key genes and proteins were closely scrutinized and discussed. (beds.ac.uk)
  • A number of intriguing candidate genes were highly differentially expressed, including a putative pollen arabinogalactan protein, a stylar Kunitz family protease inhibitor, and a stylar peptide hormone Rapid ALkalinization Factor. (beds.ac.uk)
  • TBLR1 and the homologous genes interact with proteins that regulate the nuclear hormone receptor family of transcription factors. (biomedcentral.com)
  • The LBD serves as a molecular switch that recruits co-activator or co-repressor proteins that regulate transcription of the target genes. (biomedcentral.com)
  • The IPR is controlled by PALS-22 and PALS-25, proteins of unknown biochemical function, which regulate expression of genes induced by natural intracellular pathogens. (bvsalud.org)
  • DEGs revealed upregulation of multifaceted defense related genes such as PR-protein ( EgPR-1 ) , protease inhibitor ( EgBGIA ), PRR protein ( EgLYK3 ) chitinase ( EgCht ) and expansin ( EgEXPB18 ) at 3 d.p.i and 7 d.p.i which dropped at 11 d.p.i. (biomedcentral.com)
  • I therefore have good knowledge in assaying the activities of a wide range of enzymes, characterizing interactions between genes as well as protein physical interactions using techniques such as immunoprecipitation and know how to do a screening of strains (yeast and filamentous fungi) for drugs using microplate reader. (exeter.ac.uk)
  • At the core, the bHLH-PAS transcriptional activators CLOCK and BMAL1 activate the Period ( Per1, Per2 ) and Cryptochrome ( Cry1, Cry2 ) genes, whose transcripts and proteins slowly accumulate during the daytime. (hhmi.org)
  • NP1 Protein of the Bocaparvovirus Minute Virus of Canines Controls Access to the Viral Capsid Genes via Its Role in RNA Processing. (signagen.com)
  • Aurora B has been shown to bind to end-binding protein 1 (EB1), a protein that regulates microtubule dynamics. (wikipedia.org)
  • On the other hand, the E3 ligase Itch, which contains four WW domains, regulates the stability of transcription factors, such as c-Jun and p63 ( 11 , 12 ), through regulation of their protein turnover. (aacrjournals.org)
  • Furthermore, we have also shown that WWOX competes with the WW domain-containing protein YAP for binding target proteins and thus regulates their transactivation function ( 14 ). (aacrjournals.org)
  • A mutation of the rpm-1 gene, which encodes an E3 ubiquitin ligase that negatively regulates this pathway to promote synaptogenesis, suppresses only the mec-15 cell-body defect. (genetics.org)
  • In this article, we describe the molecular and phenotypic characterization of mec-15 , which defines an additional ubiquitin ligase pathway that regulates multiple aspects of TRN development. (genetics.org)
  • The diversity of these phenotypes is consistent with the finding that mec-15 encodes an F-box protein that likely regulates protein degradation. (genetics.org)
  • hCDC4 (FBW7, FBXW7) is a new potential tumor suppressor gene which provides substrate specificity for SCF (Skp-Cullin-F-box) ubiquitin ligases and thereby regulates the degradation of potent oncogenes such as cyclin E, Myc, c-Jun and Notch. (medsci.org)
  • mTOR regulates protein synthesis in part by phosphorylating and releasing the negative regulator of translation 4EBP1 from eIE4E, an initiation factor that binds the 7-methyl-guanosine cap on mature mRNAs, and by phosphorylating and activating S6 kinase, which has numerous downstream translation regulatory targets ( Fig. 1 ). (aacrjournals.org)
  • Van Rechem and colleagues show that KDM4A regulates protein synthesis in the cytoplasm through its association with translation initiation factors. (aacrjournals.org)
  • The ubiquitin proteasome system (UPS) is an essential metabolic constituent of cellular physiology that tightly regulates cellular protein concentrations with specificity and precision to optimize cellular function. (jci.org)
  • These findings indicate that Cks1, as well as Skp2, regulates the expression level of p27 protein in gastric carcinomas. (aacrjournals.org)
  • This review is focused on a conserved ubiquitin ligase complex known as SCF that plays a key role in marking a variety of regulatory proteins for destruction by the 26S proteasome. (nih.gov)
  • An SCF-like ubiquitin ligase complex that controls presynaptic differentiation. (nih.gov)
  • To test whether the SCF-Slimb interaction is essential for neddylation-mediated Slimb turnover, we examined the protein stability of Myc-SlimbΔfbx that cannot be incorporated into the SCF complex because of the truncation of the F-box47. (nih.gov)
  • The jasmonate receptor is a multi-component complex, composed of Arabidopsis SKP-LIKE PROTEIN1 (ASK1), CORONATINE INSENSITIVE 1 (COI1), inositol phosphate (InsP), and jasmonate ZIM-domain protein (JAZ). (frontiersin.org)
  • a multiple component complex of Arabidopsis SKP-LIKE PROTEIN1 (ASK1), COI1, and Jasmonate ZIM-domain protein 1 (JAZ1). (frontiersin.org)
  • We identify the Caenorhabditis elegans SCF PROM-1 E3 ubiquitin-ligase complex as functioning to downregulate mitotic cell cycle protein levels including cyclin E, WAPL-1 , and KNL-2 at meiotic entry and, independently, promoting homologous chromosome pairing as a positive regulator of the CHK-2 kinase. (genetics.org)
  • CUL1 is the functional cullin for the SCF(ZTL) complex. (uniprot.org)
  • Here, we evaluated the effects of the functional interactions of ERK proteins with dual-specificity phosphatase 1 (DUSP1), a specific inhibitor of ERK, and S-phase kinase-associated protein 2 (SKP2)/CDC28 protein kinase 1b (CKS1) ubiquitin ligase complex in human hepatocellular carcinoma (HCC). (aacrjournals.org)
  • These results demonstrate that CUL1 is required for TOC1 degradation and further suggest that this protein is the functional cullin for the SCF(ZTL) complex. (washington.edu)
  • Here we identify a direct interaction between the catalytic domain of Aurora-A and a site flanking Myc Box I that also binds SCFFbxW7 We determined the crystal structure of the complex between Aurora-A and this region of N-Myc to 1.72-Å resolution. (icr.ac.uk)
  • However, the system fails to detect protein-protein interactions that require the presence of additional components of a multisubunit complex. (elsevier.com)
  • Here we demonstrate that the vector YIpDCE1 can be used to express elongins B and C in yeast, and that these proteins form a stable complex that interacts with the von Hippel-Lindau tumor-suppressor gene product (pVHL). (elsevier.com)
  • Only when pVHL and elongins B and C (VBC) are present does an interaction with the cullin family member, hCUL-2, occur, forming the heterotetrameric pVHL/elongin BC/hCUL-2 complex. (elsevier.com)
  • Thus, it seems possible that pVHL/elongin BC/hCUL-2 complex will possess ubiquitin ligase activity targeting specific proteins for degradation by the proteasome. (elsevier.com)
  • The tumor suppressor Fbxw7 (F-box and WD-40 domain protein 7), a subunit of an SCF-type ubiquitin ligase complex, induces the degradation of positive regulators of the cell cycle. (elsevier.com)
  • A family of structurally-related proteins that were originally identified by their ability to complex with cyclin proteins (CYCLINS). (wakehealth.edu)
  • Abundantly expressed throughout the cell cycle, Cdt1 is ubiquitinated by the ubiqutin ligase complex SCF skp2 during S and G 2 phases and degraded by proteasome. (mbl.co.jp)
  • During M and G 1 phases, Geminin is ubiquitinated by the E3 ligase complex APCcdh1 and degraded by the proteasome. (mbl.co.jp)
  • The pVHL-associated SCF ubiquitin ligase complex: molecular genetic analysis of elongin B and C, Rbx1 and HIF-1alpha in renal cell carcinoma. (ox.ac.uk)
  • Oct4 drives the expression of Nipp1 and Ccnf that inhibit the activity of the protein phosphatase 1 (PP1) complex to establish hyperphosphorylation of the retinoblastoma protein 1 (pRb) as a hallmark feature of self-renewing mESCs. (wiley.com)
  • The PER and CRY proteins associate and translocate into the nucleus during the evening and physically interact with the CLOCK:BMAL1 complex to repress their own transcription. (hhmi.org)
  • We propose that the affinity of substrate-E3 interaction, ligase activity and E1 activity are three major determinants for substrate ubiquitylation and thereby substrate degradation in vivo. (nih.gov)
  • Unlike the increased level of Arm, the Ci155 protein level is instead downregulated in both CSN5 and CSN4 mutant cells (Fig. 2a,b), suggesting that neddylated SCFSlimb degrades more Ci155, despite the reduced levels of both Cul142 and the substrate receptor Slimb (Fig. 1a) in CSN mutants. (nih.gov)
  • Subsequently, E2 ubiquitin-conjugating enzyme binds ubiquitin and delivers it to the substrate, via binding to the E3 ubiquitin ligase that specifically binds the target substrate. (plantcell.org)
  • The highly conserved protein consists of an NH2 terminal F-box and seven WD40 repeats in the COOH terminal region and acts as an adaptor protein providing substrate specificity for SCF (Skp-Cullin-F-box) ubiquitin ligases which are involved in tagging proteins for degradation in the proteasome. (medsci.org)
  • Objective FBXW7 encodes the substrate recognition component of a ubiquitin ligase that degrades targets such as Notch1, c-Jun, c-Myc and cyclin E. FBXW7 mutations occur in several tumour types, including colorectal cancers. (bmj.com)
  • G, Hampl A, Zdrahal Z, Bryja V. Dishevelled is a NEK2 kinase substrate controlling dynamics of centrosomal linker proteins. (utoronto.ca)
  • The need for high substrate specificity and the large number of known F-box proteins in yeast and worms [2] [4] suggest the existence of a large family of mammalian F-box proteins. (embl.de)
  • Deleting the C-terminal 233 amino acids of SMG abrogates F-box protein interaction and confers immunity to degradation. (princeton.edu)
  • Fucci-G 1 Orange is a fusion protein of a fragment of human Cdt1 (amino acids 30-120) with the orange fluorescent mKO2 (monomeric Kusabira-Orange2) that indicates the G 1 phase. (mbl.co.jp)
  • Fucci-S/G 2 /M Green is a fusion protein of a fragment of human Geminin (amino acids 1-110) with the green fluorescent protein mAG1 (monomeric Azami-Green1) that visualizes S, G 2 and M phases. (mbl.co.jp)
  • The F-box is a protein motif of approximately 50 amino acids that functions as a site of protein-protein interaction. (emmlaroca.com)
  • In Nicotiana benthamiana leaves, SYMRK-yellow fluorescent protein was localized at the plasma membrane, and interaction with SINAs, as determined by bimolecular fluorescence complementation, was observed in small punctae at the cytosolic interface of the plasma membrane. (plantcell.org)
  • We have previously shown that the first WW domain of WWOX mediates protein-protein interaction with proline-tyrosine (PY)-rich motifs class I, PP x Y ( 7 ). (aacrjournals.org)
  • Here, we describe a physical and functional interaction between the WWOX tumor suppressor and the activating protein-1 (AP-1) transcription factor component c-Jun. (aacrjournals.org)
  • In a serial binding assay, HBZ interacted with cullin 1 (CUL1) through a head-to-tail interaction. (asm.org)
  • Second, we have undertaken a bioinformatics analysis based on binary protein interaction data to produce putative interaction networks of MAPs. (ox.ac.uk)
  • Informative regions of the map could be highlighted by searching for paralogous interactions and by clustering proteins on the basis of their interaction profiles. (biomedcentral.com)
  • In a yeast two-hybrid assay, the two proteins to be tested for interaction are expressed with amino-terminal fusion moieties in the yeast Saccharomyces cerevisiae . (biomedcentral.com)
  • Pairs of BD and AD fused proteins can then be tested for interaction by mating the appropriate pair of yeast strains and assaying reporter activity in the resulting diploid cells [ 2 ]. (biomedcentral.com)
  • Systematic protein-protein interaction mapping for clinically relevant human GPCRs. (utoronto.ca)
  • Complete understanding of cellular function requires knowledge of the composition and dynamics of protein interaction networks, the importance of which spans all molecular cell biology fields. (springernature.com)
  • Coupling this method to biotin affinity enrichment and mass spectrometry negates many of the solubility and interaction strength issues inherent in traditional AP-MS methods, and provides unparalleled spatial context for protein interactions. (springernature.com)
  • Here we describe the parallel implementation of both BioID and FLAG AP-MS allowing simultaneous exploration of both spatial and temporal aspects of protein interaction networks. (springernature.com)
  • others contained either different protein-protein interaction modules or no recognizable motifs. (embl.de)
  • Here, we identify the E3 ubiquitin ligase Mind bomb (Mib1) as a new interaction partner of Plk4. (biologists.org)
  • Here, we report on a new interaction between Plk4 and the E3 ubiquitin ligase Mind bomb 1 (Mib1). (biologists.org)
  • As many F-box proteins can be found in sequence databases, it appears that a host of cellular pathways will be regulated by SCF-dependent proteolysis. (nih.gov)
  • The current study was designed to test the hypothesis that hibernators use periodic arousal to increase protein anabolism that compensates for the continuous muscle proteolysis during disuse. (healthdocbox.com)
  • Cardiomyocytes showed an increase in proteolysis by activating autophagy and the ubiquitin proteasome system, and a decrease in protein synthesis by decreasing P70S6K. (bvsalud.org)
  • Human Cdk subunit 1 ( Cks1 ), as well as S-phase kinase-associated protein 2 ( Skp2 ), is an essential and specific factor in the p27 proteolysis by SCF Skp2 ubiquitin ligase. (aacrjournals.org)
  • These findings may suggest that WW domain-containing proteins may compete to regulate multiple cellular processes, such as transcription and protein turnover, through their ability to interact with target proteins. (aacrjournals.org)
  • Post-translational modifications can regulate function, localization and turn-over of every cell protein impacting on cell morphology, activity and interactions in the multi-cellular organism. (biomedcentral.com)
  • As one type of post-translational modification (PTM), the main function of the UPS is mediating the degradation of cellular proteins. (biomedcentral.com)
  • Aurora B kinase is a protein that functions in the attachment of the mitotic spindle to the centromere. (wikipedia.org)
  • Intriguingly, EB1 overexpression enhances Aurora B kinase activity, at least in part because EB1 blocks the dephosphorylation/inactivation of Aurora B by protein phosphatase 2A. (wikipedia.org)
  • The best-characterized RAS effector promoting cell cycle progression is the mitogen-activated protein kinase (MAPK) pathway ( 9 ). (aacrjournals.org)
  • In this cascade, RAS induction triggers activation of RAF, MAPK kinase kinase (MEK), and extracellular signal-regulated kinase (ERK) proteins, leading to up-regulation of c-FOS, c-JUN, c-MYC, and ETS targets ( 9 ). (aacrjournals.org)
  • Shown are receptor tyrosine kinase (RTK) and glucose signaling axes that elicit control on mTORC1, a key regulator of protein synthesis. (aacrjournals.org)
  • Ecdysone-inducible expression of oncogenic Ha-Ras in NIH 3T3 cells leads to transient nuclear localization of activated extracellular signal-regulated kinase regulated by mitogen-activated protein kinase phosphatase-1. (icr.ac.uk)
  • The Ras family of GTP-binding proteins are key transducers of extracellular signals, particularly through the mitogen-activated protein kinase (MAPK) pathway. (icr.ac.uk)
  • Inhibition of the protein kinase WEE1 synergizes with chemotherapy in preclinical models and WEE1 inhibitors are being explored as potential cancer therapies. (icr.ac.uk)
  • The encoded protein promotes apoptosis by dephosphorylating and inactivating the serine/threonine kinase Akt, and functions as a tumor suppressor in multiple types of cancer. (mybiosource.com)
  • S-Phase Kinase-Associated Proteins" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (wakehealth.edu)
  • This graph shows the total number of publications written about "S-Phase Kinase-Associated Proteins" by people in this website by year, and whether "S-Phase Kinase-Associated Proteins" was a major or minor topic of these publications. (wakehealth.edu)
  • Below are the most recent publications written about "S-Phase Kinase-Associated Proteins" by people in Profiles. (wakehealth.edu)
  • Putative Membrane Receptors Contribute to Activation and Efficient Signaling of Mitogen-Activated Protein Kinase Cascades during Adaptation of Aspergillus fumigatus to Different Stressors and Carbon Sources. (exeter.ac.uk)
  • In eukaryotes, the bulk of the protein degradation that occurs in the cytoplasm and nucleus is carried out by the 26S proteasome. (nih.gov)
  • After translation of viral RNAs into HBV proteins occurs in the host cytoplasm, viral pgRNA is encapsulated into core particles. (biomedcentral.com)
  • Specifically, we study how proteins partition between nucleus and cytoplasm and how different nuclear composition affects cellular function. (princeton.edu)
  • The concepts of SCF ubiquitin ligase function are illustrated by analysis of the degradation pathway for the G1 cyclin Cln2. (nih.gov)
  • Thus, HMB appears to be more potent than Leu and KIC in inhibiting protein degradation in the absence or presence of insulin, and this inhibitory effect may be dependent on PI3K/Akt signaling pathway regardless of insulin, and mTOR signaling was only involved in this effect of HMB in the absence of insulin. (bireme.br)
  • fsn-1 functions in the same pathway as rpm-1, a gene encoding a large protein with RING finger domains. (nih.gov)
  • Thus, MEC-15 acts in parallel with RPM-1 , implicating a second protein degradation pathway in TRN development. (genetics.org)
  • In this study, we showed that exacerbated hypertrophy induced by pressure overload in cardiac-deleted Pak1 mice was attributable to a failure to upregulate the antihypertrophic E3 ligase, Fbxo32, responsible for targeting proteins for the ubiquitin-degradation pathway. (ahajournals.org)
  • KDM4A depletion was then shown to result in decreased global protein synthesis, an effect also seen with rapamycin, the pioneering inhibitor of the mTOR signaling pathway. (aacrjournals.org)
  • They play an important role in the protein degradation pathway by becoming components of SKP CULLIN F-BOX PROTEIN LIGASES, which selectively act on a subset of proteins including beta-catenin and IkappaBbeta. (bireme.br)
  • A plasmid containing Skp2 siRNA was used to decrease the high constitutive level of Skp2 protein in rTF, which can lead to consequent degradation of p27 kip1 . (arvojournals.org)
  • Here, we show that the F-box protein Skp2 is polyubiquitinated, and hence earmarked for destruction, by APC CDH1 . (elsevier.com)
  • Western blot analysis showed that Cks1/Skp2-cotransfected cells expressed a much lower level of p27 protein than the controls. (aacrjournals.org)
  • SMAX1 is a member of an eight-gene family in Arabidopsis that has weak similarity to HEAT SHOCK PROTEIN 101 , which encodes a caseinolytic peptidase B chaperonin required for thermotolerance. (plantphysiol.org)
  • The HTLV-1 genome encodes three common retroviral structural and enzymatic proteins ( gag , pol , and env proteins) and is flanked by long terminal repeats (LTR) at each end. (asm.org)
  • The plus strand of the pX region encodes regulatory and accessory proteins, including p12 I , p21 I , p13 II , p30 II , Rex, and Tax ( 7 ). (asm.org)
  • Among the viral transcripts, preC mRNA encodes precore protein. (biomedcentral.com)
  • Fucci-S/G 2 /M Green (N+C) encodes a fusion protein of a part of human Geminin (1-60) with mAG1. (mbl.co.jp)
  • A single highly conserved gene encodes a small family of protein molecules. (biomedcentral.com)
  • The most affected processes belong to the categories "stress responses," "protein metabolism" and "secondary metabolism," highlighting the intrinsic capacity of grape berries to perceive HT and to build adaptive responses. (frontiersin.org)
  • We discovered that proteins involved in "post-embryonic development" and "metabolic pathways" such as carbohydrate and nitrogen metabolism could be used to construct a developmentally associated network. (beds.ac.uk)
  • Furthermore, we discussed the potential function of several vital DAPs from GO and KEGG analyses that were closely related to histone modification, ubiquitin-mediated protein degradation, transcription factors, carbohydrate and nitrogen metabolism and heat shock proteins (HSPs). (beds.ac.uk)
  • The effect of myostatin on protein metabolism is related to fiber type composition, which may be associated to the extent of atrophy mediated effect of myostatin on muscle. (bvsalud.org)
  • (b) The F-box protein β-TRCP controls DNA damage-induced cell cycle arrest, cessation of DNA damage signaling, and recovery from cell cycle arrest. (nih.gov)
  • SCF PROM-1 is thus a novel regulator of meiotic entry, coordinating downregulation of mitotic cell cycle proteins and promoting homolog pairing. (genetics.org)
  • We screened the arrays using a novel pooled mating approach, initially focusing on proteins related to cell-cycle regulators. (biomedcentral.com)
  • F-box proteins are an expanding family of eukaryotic proteins characterized by an approximately 40 aminoacid motif, the F box (so named because cyclin F was one of the first proteins in which this motif was identified) [1]. (embl.de)
  • Since mec-15 phenotypes depend on the relative levels of these tubulins, MEC-15 may target proteins whose function is affected by these levels. (genetics.org)
  • Expression quantitative trait loci (eQTLs) regulate expression of mRNA or protein and originate from transcript-level polymorphisms of a single gene with a specific chromosomal location. (springeropen.com)
  • 2003), the molecular mechanisms that regulate the balance between muscle protein synthesis and degradation have not been clarified in this natural muscle system of hibernators. (healthdocbox.com)
  • We previously showed that PALS-22 and PALS-25 regulate the mRNA expression of the predicted ubiquitin ligase component cullin cul-6, which promotes thermotolerance in pals-22 mutants. (bvsalud.org)
  • The study provides further evidence, in addition to existing literature, that plant E3 ligases are exploited by geminiviruses to enhance pathogenicity. (researchsquare.com)
  • Plant E3 ligases are subdivided into 11 classes: the RING (Really Interesting New Gene), the CRL (Cullin RING), the RBR (RING-between-RING RING), the HECT (Homologous to E6-associated protein C-terminus) (Morreale and Walden, 2016 ), the U-Box (Hatakeyama et al. (researchsquare.com)
  • Given that general proteasome inhibitors are currently used as anticancer agents, a better understanding of the ubiquitylation of specific targets by specific ubiquitin ligases may result in improved cancer therapeutics. (nih.gov)
  • The ubiquitylation of proteins is reprogrammed by plant geminiviruses which alter the ubiquitin proteasome system (UPS) to fully infect the host. (researchsquare.com)
  • The E3 ligase activity of Mib1 triggers ubiquitylation of Plk4 on multiple sites, causing the formation of Lys11‐, Lys29‐ and Lys48‐ubiquitin linkages. (biologists.org)
  • Multiplexed proteomics is a powerful tool to assay cell states in health and disease, but accurate quantification of relative protein changes is impaired by interference from co-isolated peptides. (princeton.edu)
  • Leucine (Leu) and its metabolites α-ketoisocaproate (KIC) and -hydroxy- -methyl butyrate (HMB) are potent regulators of protein turnover. (bireme.br)
  • Our results implicate SINA4 E3 ubiquitin ligase in the turnover of SYMRK and provide a conceptual mechanism for its symbiosis-appropriate spatio-temporal containment. (plantcell.org)
  • We find that Merkel cell polyomavirus (MCV), a life-long human infection that can cause Merkel cell carcinoma, persists as a nonreplicating, silent infection owing to the continuous cellular turnover of its replication protein. (pnas.org)
  • Adverse cellular conditions, such as nutrient starvation, inhibit networks controlling MCV replication protein turnover and signal the virus to spread to uninfected cells or to a new host. (pnas.org)
  • ZEITLUPE (ADO1/ZTL) is the F-box protein that associates with the SCF (for Skp/Cullin/F-box) E3 ubiquitin ligase that is responsible for marking APRR1/TOC1 for turnover. (uniprot.org)
  • Extensor digitorum longus muscles and C2C12 myotubes exhibited a reduction in protein turnover. (bvsalud.org)
  • Vpu induces the expression of four microRNAs that target mRNAs encoding proteins required for peroxisome formation and metabolic function. (asm.org)
  • On the one hand, the UPS acts as a host defense mechanism to selectively recognize HBV proteins as well as special cellular proteins that favor the viral life cycle and induces their ubiquitin-dependent proteasomal degradation to limit HBV infection. (biomedcentral.com)
  • MDM2 binding induces a conformational change in p53 that is opposed by heat-shock protein 90 and precedes p53 proteasomal degradation. (rush.edu)
  • A more recently developed method called BioID employs the expression of bait proteins fused to a nonspecific biotin ligase, BirA*, that induces in vivo biotinylation of proximal proteins. (springernature.com)
  • Expression of Aurora B reaches a maximum at the G2-M transition, whereas Aurora B protein is most active during mitosis. (wikipedia.org)
  • They function in combination with the E2 enzyme Cdc34 to ubiquitinate G1 cyclins, Cdk inhibitors and many other proteins, to mark them for degradation. (embl.de)
  • have now confirmed that the circadian clock does indeed participate in the DNA damage response and have revealed that two proteins known to be involved in the circadian clock- Cryptochrome 1 and 2 -have a central role in protecting the integrity of the genetic information in the cell. (elifesciences.org)
  • However, it was unclear whether CUL-6 acted alone, or together with other cullin-ring ubiquitin ligase components, which comprise a greatly expanded gene family in C. elegans Here we use coimmunoprecipitation studies paired with genetic analysis to define the cullin-RING ligase components that act together with CUL-6 to promote thermotolerance. (bvsalud.org)
  • Accordingly, C. elegans employs three post-transcriptional pathways, SCF PROM-1 -mediated protein degradation, GLD-1-mediated translational repression, and GLD-2-mediated translational activation, to control and coordinate the initiation of meiotic development. (genetics.org)
  • Thus, modulation of protein levels by proteosome pathways plays a critical role in regulating the development of neurons in C. elegans . (genetics.org)
  • Protein degradation is deployed to modulate the steady-state abundance of proteins and to switch cellular regulatory circuits from one state to another by abrupt elimination of control proteins. (nih.gov)
  • Protein-mediated viral latency through cellular SCF E3 ligase targeting of viral replication proteins is a unique form of latency that may promote chronic viral persistence for some small DNA and RNA viruses. (pnas.org)
  • Here, we show that the HIV-1 accessory protein Vpu is necessary and sufficient for the depletion of cellular peroxisomes during infection. (asm.org)
  • Derived from a single cell, all cells of a multi-cellular organism possess the same DNA sequences in their whole genome and thus their various phenotypes must be the result of differences in transcriptional and post-transcriptional regulation of cellular proteins secondary to intra-cellular and external signals. (biomedcentral.com)
  • Moreover, in the infected hepatocytes, certain cellular proteins that are dependent on the UPS are involved in abnormal biological processes which are mediated by HBV. (biomedcentral.com)
  • Some F-box proteins have been shown to be critical for the controlled degradation of cellular regulatory proteins [2] [3]. (embl.de)
  • Our findings reveal a novel functional cross-talk between c-Jun transcription factor and WWOX tumor suppressor protein. (aacrjournals.org)
  • Its ability to ubiquitinate p53 is regulated by TUMOR SUPPRESSOR PROTEIN P14ARF. (rush.edu)
  • Posttranscriptional regulation, in particular the temporally regulated proteasomal degradation of specific clock proteins, is critical to the clock mechanism ( Gallego and Virshup, 2007 ). (plantphysiol.org)
  • We have demonstrated that both mutated proteins exhibit enhanced polyubiquitination (or polyubiquitylation) and proteasomal degradation. (elsevier.com)
  • WWOX contains two WW domains that mediate protein-protein interactions. (aacrjournals.org)
  • Further experiments are needed to work out how these proteins influence the activity of BMAL1 and CLOCK, and to investigate the seemingly conflicting roles of the two cryptochromes and the interactions between them. (elifesciences.org)
  • The yeast two-hybrid system is a powerful technique that detects interactions between two proteins and has been useful in identifying new binding partners. (elsevier.com)
  • Maps depicting binary interactions between proteins can be powerful starting points for understanding biological systems. (biomedcentral.com)
  • In the most extensive screen to date, a Gal4-based two-hybrid system was used recently to detect over 20,000 interactions among Drosophila proteins. (biomedcentral.com)
  • Although these data are a valuable resource for insights into protein networks, they cover only a fraction of the expected number of interactions. (biomedcentral.com)
  • We detected 1,814 reproducible interactions among 488 proteins. (biomedcentral.com)
  • Protein-protein interactions have an essential role in a wide variety of biological processes. (biomedcentral.com)
  • Maps depicting the possible binary interactions among proteins can therefore provide clues not only about the functions of individual proteins but also about the structure and function of entire protein networks and biological systems. (biomedcentral.com)
  • One of the most powerful technologies used in recent years for mapping binary protein interactions is the yeast two-hybrid system [ 1 ]. (biomedcentral.com)
  • To map interactions among large sets of proteins, the BD and AD expression vectors are placed initially into different haploid yeast strains of opposite mating types. (biomedcentral.com)
  • Traditional AP-MS methods are well suited to providing information regarding the temporal aspects of soluble protein-protein interactions, but the requirement to maintain protein-protein interactions during cell lysis and AP means that both weak-affinity interactions and spatial information is lost. (springernature.com)
  • Almost all of these regulatory proteins have been identified in different plant species. (plantcell.org)
  • Notably, protein synthesis inhibition and sensitivity to several mTOR inhibitors were potentiated by KDM4A depletion or small molecule inhibition in HEK 293T cells, suggesting a rational combination therapy. (aacrjournals.org)
  • WWOX is a tumor suppressor that functions as a modular protein partner of transcription factors. (aacrjournals.org)
  • Levels of DUSP1, as assessed by real-time reverse transcription-PCR and Western blot analysis, were significantly higher in tumors with better prognosis (as defined by the length of patients' survival) when compared with both normal and nontumorous surrounding livers, whereas DUSP1 protein expression sharply declined in all HCC with poorer prognosis. (aacrjournals.org)
  • One protein is fused to a DNA-binding domain (BD) and the other is fused to a transcription activation domain (AD). (biomedcentral.com)
  • The CLOCK protein acts as a heterodimeric transcription factor with a partner known as BMAL1 (ARNTL). (hhmi.org)
  • Among these mechanisms, ubiquitin-mediated degradation of key proteins has an important role in the regulation of the DDR, centrosome duplication and chromosome segregation. (nih.gov)
  • 2004). Upregulation (or balanced regulation) of several molecular chaperones (e.g., heat shock protein 70) examined during winter dormancy might further imply the significance of periodic arousals for muscle retention (Lee et al. (healthdocbox.com)
  • Li S, Shu B, Zhang Y, Li J, Guo J, Wang Y, Ren F, Xiao G, Chang Z, Chen D. Carboxyl terminus of Hsp70-interacting protein regulation of osteoclast formation in mice through promotion of tumor necrosis factor receptor-associated factor 6 protein degradation. (rush.edu)
  • PHLPP: a pleckstrin homology domain leucine-rich repeat protein phosphoserine and ¿threonine phosphatase. (mybiosource.com)