• The protein complex SCFβ-TrCP1/2 is an E3 ubiquitin ligase that functions in Wee1A ubiquitination. (wikipedia.org)
  • This active complex may provide multiple E2 active sites, enabling efficient ubiquitination of substrates. (rcsb.org)
  • In this review, we will discuss recent advances on the functions of Cul3 ubiquitin ligases in cancer development, progression, and therapeutic response and the dysregulation of Cul3-mediated ubiquitination events in human malignancies. (tmu.edu.tw)
  • Mechanistically, TMEM127 binds to RET and recruits the NEDD4 E3 ubiquitin ligase for RET ubiquitination and degradation via TMEM127 C-terminal PxxY motifs. (stanford.edu)
  • Mechanistically, SUSD6 forms a trimolecular complex with TMEM127 and MHC-I, which recruits WWP2 for MHC-I ubiquitination and lysosomal degradation. (stanford.edu)
  • Ubiquitination targets proteins for degradation and is a potent regulator of cellular protein function. (embl-heidelberg.de)
  • Moreover, we observed that PUS10 is ubiquitinated by E3 ubiquitin ligase CRL4DCAF1 complex and the increase of PUS10 in aged HSPC is due to aging-declined CRL4DCAF1- mediated ubiquitination degradation signaling. (haematologica.org)
  • In simple terms, the process is like a cell taking unused documents (aberrant proteins) to its secretary (E3 enzyme), stamping them with an obsolete stamp (ubiquitination), and throwing them into a shredder (proteasome). (huatengsci.com)
  • This enables the E3 ligase complex to catalyze ubiquitination of the target. (cisbio.net)
  • The S. cerevisiae protein Swe1 is also regulated by degradation. (wikipedia.org)
  • In yeast, the glucose-induced degradation-deficient (GID) E3 ligase selectively degrades superfluous gluconeogenic enzymes. (elifesciences.org)
  • Particularly in yeast, an organism where gluconeogenesis and glycolytic activity are intermittently coordinated, the multi-subunit GID E3 ligase complex specifically targets the surplus of gluconeogenic enzymes, including the conserved Fructose-1,6-bisphosphatase 1 (Fbp1), for proteasomal degradation. (elifesciences.org)
  • The COP9/signalosome (CSN) is a highly conserved eight subunit complex that, by deneddylating cullins in cullin-based E3 ubiquitin ligases, regulates protein degradation. (biomedcentral.com)
  • These proteins were rescued by the proteasome inhibitor MG132, indicating the autocatalytic degradation of F-box proteins upon loss of CSN2 or CSN5. (biomedcentral.com)
  • The regulated expression and degradation of proteins are critical to all aspects of cell development and proliferation. (biomedcentral.com)
  • A key component involved in regulating degradation of proteins by the UPS is the COP9 signalosome (CSN). (biomedcentral.com)
  • Loss of TMEM127 altered normal cell membrane organization and recruitment and stabilization of membrane protein complexes, impaired assembly, and maturation of clathrin coated pits, and reduced internalization and degradation of cell surface RET. (stanford.edu)
  • Many cell-cycle regulators are targeted for degradation by being tagged with chains of the small protein ubiquitin. (nature.com)
  • Mechanistically, we found that Rab40c binds the protein phosphatase 6 (PP6) complex and ubiquitylates one of its subunits, ankyrin repeat domain 28 (ANKRD28), thus leading to its lysosomal degradation. (life-science-alliance.org)
  • The human ubiquitin-proteasomesystem (UPS) is the main pathway of intracellular protein degradation, which is involved in more than 80% of intracellular protein degradation. (huatengsci.com)
  • The concept of targeted protein degradation challenges conventional rules for pharmaceutical drug discovery. (cisbio.net)
  • Rather than directly modify protein function by occupying an active site, PROteolysis TArgeting Chimeras (PROTACs) exploit the cell's own degradation machinery to irreversibly destroy target proteins. (cisbio.net)
  • PROteolysis TArgeting Chimeras (PROTACs) are small two-headed (heterobifunctional) molecules that hijack the cell's protein degradation machinery to irreversibly destroy the target. (cisbio.net)
  • The resulting polyubiquitin chain flags the target protein for degradation by the proteasome. (cisbio.net)
  • The resulting ternary complex catalyzes polyubiquitination of the target protein, tagging it for degradation by the proteasome. (cisbio.net)
  • The proteostasis network (PN) is an assembly of distinct dynamic molecular pathways that control the functionality of the proteome (proteome homeodynamics) during protein synthesis, folding, trafficking, and degradation. (hindawi.com)
  • It is now well established that Myc levels are in part regulated by ubiquitin-dependent proteasomal degradation. (silverchair.com)
  • In these complexes, the Cullin protein serves as a scaffold to connect two functional modules of the ligases, the catalytic subunit and substrate-binding subunit. (tmu.edu.tw)
  • Greater than 95% knockdown of the non-catalytic subunit CSN2 and the deneddylating subunit CSN5 of the CSN was achieved in the human myeloid progenitor cell line K562. (biomedcentral.com)
  • Since each cullin (Cul1-5) forms complexes with a variable substrate recognition subunit (SRS) (F-box proteins for Cul1 as above, VHL box proteins for Cul2, BTB proteins for Cul3, WD40 proteins for Cul4 and SOCS box proteins for Cul5, reviewed in [ 20 ]) specificity in CRL target protein recruitment is achieved by the large number of variable SRS containing CRLs. (biomedcentral.com)
  • Structural basis for the subunit assembly of the anaphase-promoting complex. (ox.ac.uk)
  • The means by which the activity of the catalytic subunit of CSN (CSN5) is regulated is not fully understood and thus new tools are required to study its activity. (gla.ac.uk)
  • and Atg13, the regulatory subunit of the Atg1p signaling complex that stimulates Atg1p kinase activity and is essential for vesicle formation for the duration of autophagy and cytoplasm-to-vacuole targeting. (atminhibitor.com)
  • Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. (icr.ac.uk)
  • In this work, we have revealed that early viral protein UBCv1, the only known conjugating enzyme encoded by a virus, modulates innate immune and inflammatory signaling. (mdpi.com)
  • Transcriptomic analysis of the two recombinant strains in comparison with the control strain showed that the correct folding of proteins assisted by molecular chaperones played a key role in the improvement of FumDM expression and its enzyme activity. (inra.fr)
  • Based on the acetylcholinesterase/choline oxidase dual enzyme-mediated cascade catalytic reactions of Fe(2+)/Fe(3+) transformation, a ratiometric fluorescence sensing scheme is developed. (inra.fr)
  • Here, we identified all subunits of the mammalian GID/CTLH complex and provide a comprehensive map of its hierarchical organization and step-wise assembly. (elifesciences.org)
  • Our structure explains how this TPR sub-complex, together with additional scaffolding subunits (Apc1, Apc4 and Apc5), coordinate the juxtaposition of the catalytic and substrate recognition module (Apc2, Apc11 and Apc10 (also known as Doc1)), and TPR-phosphorylation sites, relative to co-activator, regulatory proteins and substrates. (ox.ac.uk)
  • Solving the structure of protein complexes is particularly challenging when they contain many subunits. (nature.com)
  • One of the most complex ubiquitin ligases is the anaphase-promoting complex (APC) - a 1.5-megadalton assemblage of 1-2 copies of each of 13 different subunits, as well as two diffusible activators. (nature.com)
  • 2015) . Jarid2 methylation via the PRC2 complex regulates H3K27me3 deposition during cell differentiation . (sdbonline.org)
  • miR-34a negatively regulates mTORC1 and may also contribute to abnormal corticogenesis in tuberous sclerosis complex (TSC). (medscape.com)
  • Peli1 regulates the activation of a metabolic kinase, mTORC1, through its interaction with mTORC1 inhibitory proteins TSC1 and TSC2. (medscape.com)
  • Baculoviral IAP repeat-containing protein 6 (BIRC6), a giant IAP with dual E2 and E3 ubiquitin ligase activity, regulates programmed cell death through unknown mechanisms. (ox.ac.uk)
  • In addition to its effects on dMyc, Puf regulates both Ago and its cell cycle substrate Cyclin E. Therefore, Puf influences cell growth by controlling the stability of key regulatory proteins. (silverchair.com)
  • Interestingly, altered F-box protein gene expression was also observed in CSN2 and CSN5 knockdowns, suggesting a potential role of the CSN in regulating F-box protein transcription. (biomedcentral.com)
  • The TMEM127 gene encodes a transmembrane protein of poorly known function that is mutated in pheochromocytomas, neural crest-derived tumors of adrenomedullary cells. (stanford.edu)
  • Jumonji (JmjC) domain proteins (see Jarid2 ) influence gene expression and chromatin organization by way of histone demethylation, which provides a means to regulate the activity of genes across the genome. (sdbonline.org)
  • Histone deacetylase complexes remove histone acetylation, thereby repressing transcription and regulating the transcriptional output of each gene. (diamond.ac.uk)
  • This cluster incorporated GO terms like "signal transduction," "ubiquitinprotein ligase activity," and "positive regulation of gene expression" (supplemental Fig. S2H). (atminhibitor.com)
  • Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast Schizosaccharomyces pombe (S. pombe). (wikipedia.org)
  • The corresponding proteins are Wee1-like protein kinase and Wee1-like protein kinase 2 which act on the human Cdk1 homologue Cdk1. (wikipedia.org)
  • Equipped with a mouse model of stress (5-HT1A-R-/- mice) and a 5-HT1A-R-expressing hippocampal neuron-derived cell line, HN2-5, our earlier studies have reported that a 5-HT1A-R-mediated signaling pathway functions via extracellular receptor-activated kinase 1/2 (ERK1/2)-catalyzed activation of protein kinase C alpha (PKC) to promote synaptogenesis at P15 in the hippocampal CA1 region [12,16]. (thetechnoant.info)
  • A large pore is formed by transmembrane proteins. (tcdb.org)
  • The top-ranked negative regulators were surface protein sushi domain containing 6 (SUSD6), transmembrane protein 127 (TMEM127), and the E3 ubiquitin ligase WWP2. (stanford.edu)
  • Both polypeptides are dislocated in a step mediated by the transmembrane Hrd1p ubiquitin ligase complex and subsequently degraded. (warwick.ac.uk)
  • IBR domain is a cysteine-rich (C6HC) zinc finger domain that is present in Triad1, and which is conserved in other proteins encoded by various eukaryotes. (embl.de)
  • With the existence of a large number of BTB proteins in human, the Cul3 ubiquitin ligases ubiquitinate a wide range of substrates involving in diverse cellular functions. (tmu.edu.tw)
  • Our biochemical and cellular analysis thus demonstrates that the GID/CTLH complex prevents cell cycle exit in G1, at least in part by degrading Hbp1. (elifesciences.org)
  • Cellular proteostasis involves the coordinated and compensatory action of pathways that control biogenesis, folding, trafficking and breakdown of proteins allowing the cell to adapt to physiological or pathological environmental changes. (elifesciences.org)
  • TRIM E3 ubiquitin ligases regulate a wide variety of cellular processes and are particularly important during innate immune signalling events. (figshare.com)
  • Lastly, we noticed an enrichment of predicted G4 sequences in the promoter of TOP1-repressed cellular genes.nnCONCLUSIONS: Our results demonstrate the formation of a TOP1/G4 complex on the HIV-1 LTR promoter and its repressive effect on the promoter activity. (cnrs.fr)
  • Cells express a pool of thousands of different proteins that need to be tightly controlled for proper cellular structure, organization, and function. (hindawi.com)
  • Myc proteins control multiple cellular processes, including cell growth, proliferation, metabolism and apoptosis, and deregulation of Myc plays an important role in oncogenesis ( Dang, 2012 ). (silverchair.com)
  • It disrupted the AR translational MID1 regulator complex leading to release of the associated AR mRNA and subsequently to downregulation of AR protein in AR positive cell lines. (biomedcentral.com)
  • Building on the newer pathways for pathogenesis includes the E3 ubiquitin ligase Peli1 as an important regulator of T-cell metabolism and antitumor immunity. (medscape.com)
  • Using a genetic screen for modifiers of Drosophila Myc ( dMyc )-induced growth, we identified and characterized a ubiquitin-specific protease (USP), Puffyeye (Puf), as a novel regulator of dMyc levels and function in vivo . (silverchair.com)
  • Intrinsically disordered regions in Pex13 and Pex5 resemble those found in nuclear pore complex proteins. (tcdb.org)
  • The two main routes for eukaryotic intracellular protein clearance are the ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway. (biomedcentral.com)
  • Here, we show that loss of TMEM127 causes wildtype RET protein accumulation on the cell surface, where increased receptor density facilitates constitutive ligand-independent activity and downstream signaling, driving cell proliferation. (stanford.edu)
  • Rap 1 is a member of a group of proteins involved in the regulation of cell proliferation and differentiation. (medscape.com)
  • This effect is mainly achieved via inhibition of the mitochondrial respiratory chain I complex. (biomedcentral.com)
  • Inhibition of CRLs is mediated by the COP9 signalosome complex (CSN) which cleaves the isopeptide bond binding to NEDD8 and removes it. (gla.ac.uk)
  • Mutations abolishing G4 folding affected TOP1/G4 interaction and hindered G4-dependent inhibition of TOP1 catalytic activity in vitro. (cnrs.fr)
  • In the Cul3 ubiquitin ligases, Bric-a-brac/Tramtrack/Broad complex (BTB) domain-containing proteins function as a bridge to connect Cul3 and substrates. (tmu.edu.tw)
  • Information on how its 13 constituent proteins are assembled, and how they interact with co-activators, substrates and regulatory proteins is limited. (ox.ac.uk)
  • While the BTB domain is responsible for Cul3 binding, these proteins usually contain an additional domain for substrate interaction, such as MATH, kelch, Zn finger, and PAM, Highwire, and RPM-1 (PHR domain). (tmu.edu.tw)
  • In particular, we will focus on three Cul3 substrate adaptors, kelch-like ECH-associated protein (Keap1), kelch-like family member 20 (KLHL20), and speckle type BTB/POZ protein (SPOP), with the intent to highlight novel targets in cancer therapy. (tmu.edu.tw)
  • 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)
  • Essential component of a ubiquitin-editing protein complex, comprising also RNF11, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. (icr.ac.uk)
  • Please note that proteins can be included in multiple pathways, ie. (embl.de)
  • Over the past decade there has been an explosion in the number of small molecule inhibitors targeting protein kinases that regulate key cancer-related pathways and signal transduction cascades. (cisbio.net)
  • Plants are immobile and, to overcome harsh environmental conditions such as drought, salt, and cold, they have evolved complex signaling pathways. (mdpi.com)
  • The synthesis of several activity-based probes for CSN5 was attempted, each containing a zinc-binding group (ZBG) for attachment onto the catalytic site, a NEDD8 peptide to enable selectivity to CSN5 and a biotin tag for subsequent biochemical assays. (gla.ac.uk)
  • Here we have determined the 2.2 A crystal structure of an intermediate of UbcH5b~ubiquitin (Ub) conjugate, which is assembled into an infinite spiral through the backside interaction. (rcsb.org)
  • the interaction is inhibited by HTLV-1 protein Tax. (icr.ac.uk)
  • The RING domain is a protein interaction domain that has been implicated in a range of diverse biological processes. (embl-heidelberg.de)
  • Beyond the organelle dynamics, the constant interaction with the ubiquitin-proteasome-system (UPS) has become an emerging aspect of healthy mitochondria. (hindawi.com)
  • Canonical polyubiquitylation is not a prerequisite for this interaction because a catalytically inactive Hrd1p E3 ubiquitin ligase retains the ability to retrotranslocate RTA, and variants lacking one or both endogenous lysyl residues also require the Hrd1p complex. (warwick.ac.uk)
  • ARA55, ARA54, ARA70, BRCA1, and heat-shock proteins) may allow cells to become independent of androgens (intrinsic activation). (aacrjournals.org)
  • At the same time, Wee1 is inactivated through phosphorylation at its C-terminal catalytic domain by Nim1/Cdr1. (wikipedia.org)
  • Here, we show that these characteristics of the Omicron spike protein are determined by its receptor-binding domain. (bvsalud.org)
  • CSN5 contains a JAMM domain with a Zn2+ atom facilitating its catalytic activity. (gla.ac.uk)
  • Taxonomic distribution of proteins containing RING domain. (embl-heidelberg.de)
  • The complete taxonomic breakdown of all proteins with RING domain is also avaliable . (embl-heidelberg.de)
  • Click on the protein counts, or double click on taxonomic names to display all proteins containing RING domain in the selected taxonomic class. (embl-heidelberg.de)
  • Proteins that contain two Ring fingers and an IBR domain (these proteins are also termed RBR family proteins) are thought to exist in all eukaryotic organisms. (embl.de)
  • Percentage points are related to the number of proteins with IBR domain which could be assigned to a KEGG orthologous group, and not all proteins containing IBR domain. (embl.de)
  • They are characterized by a conserved tripartite motif in their N-terminal portion which comprises a canonical RING domain, one or two B-box domains and a coiled-coil region that mediates ligase dimerization. (figshare.com)
  • The crystal structure of a complex between the TRIM25 RING domain and an ubiquitin-loaded E2 identifies the structural and mechanistic features that promote a closed E2~Ub conformation to activate the thioester for ubiquitin transfer allowing us to propose a model for the regulation of activity in the full-length protein. (figshare.com)
  • We identified DNA topoisomerase1 (TOP1) to be a potent repressor of this promoter and linked this repression to its catalytic domain. (cnrs.fr)
  • Tuberin shows a small region of homologic identity to the catalytic domain of the Rap 1 guanosine triphosphatase (GTPase) activity protein (Rap 1 GAP). (medscape.com)
  • Cryo-electron microscopy structures of BIRC6 alone and in complex with SMAC reveal that BIRC6 is an antiparallel dimer juxtaposing the substrate-binding module against the catalytic domain. (ox.ac.uk)
  • A hallmark of proteome balance is the ubiquitin-proteasome system (UPS) that degrades roughly 80% of multi-ubiquitinated proteins ( Collins and Goldberg, 2017 ). (elifesciences.org)
  • Here, the CDC48 complex is required only for RTAΔ, although the involvement of individual ATPases (Rpt proteins) in the 19S regulatory particle (RP) of the proteasome, and the 20S catalytic chamber itself, is very different for the two RTA variants. (warwick.ac.uk)
  • Pex4p is a membrane protein that may facilitate cycling of Pex5p back to the cytosol. (tcdb.org)
  • Link to all annotated objects annotated to membrane protein complex. (planteome.org)
  • Link to all direct and indirect annotations to membrane protein complex. (planteome.org)
  • However, the exact functions of Rab40c remain to be determined, and what proteins are the targets of Rab40c-Cullin5-mediated ubiquitylation in mammalian cells are unknown. (life-science-alliance.org)
  • Each heterobifunctional PROTAC molecule targets a protein of interest (POI), serving as a bridge to bring it in close proximity with an E3 ligase. (cisbio.net)
  • Indeed, Hbp1 accumulates in cells lacking GID/CTLH activity, and Hbp1 physically interacts and is ubiquitinated in vitro by reconstituted GID/CTLH complexes. (elifesciences.org)
  • The E3 ligase interacts with the protein substrate and thus confers the specificity of the UPS [ 16 ]. (biomedcentral.com)
  • We show that puf genetically and physically interacts with dMyc and the ubiquitin ligase archipelago ( ago ) to modulate a dMyc-dependent cell growth phenotype, and that varying Puf levels in both the eye and wing phenocopies the effects of altered dMyc abundance. (silverchair.com)
  • Biochemical reconstitution demonstrates that the mammalian complex possesses inherent E3 ubiquitin ligase activity, using Ube2H as its cognate E2. (elifesciences.org)
  • Disruption of the MID1-α4/PP2A complex by metformin thus leads to increased PP2A activity. (biomedcentral.com)
  • A protein complex that includes a ubiquitin-protein ligase and enables ubiquitin protein ligase activity. (planteome.org)
  • Here, we provide a detailed characterization of the TRIM ligases TRIM25 and TRIM32 and show how their oligomeric state is linked to catalytic activity. (figshare.com)
  • In this study, we observed that the expression of pseudouridine (Ψ) synthase 10 is increased in aged hematopoietic stem and progenitor cells (HSPC) and enforced protein of Ψ synthase 10 (PUS10) recapitulates the phenotype of aged HSC, which is not achieved by its Ψ synthase activity. (haematologica.org)
  • CRLs are activated by covalent attachment to the C-terminus of the ubiquitin-like modifier NEDD8 by forming an isopeptide bond in a process called NEDDylation. (gla.ac.uk)
  • Ageing leads to a gradual dysfunction of the proteostasis network and thus to proteome instability due to accumulation of damaged and/or misfolded proteins [ 2 ]. (hindawi.com)
  • Polycomb Group (PcG) proteins maintain transcriptional repression throughout development, mostly by regulating chromatin structure. (sdbonline.org)
  • Chen, HY & Chen, RH 2016, ' Cullin 3 ubiquitin ligases in cancer biology: Functions and therapeutic implications ', Frontiers in Oncology , vol. 6, no. (tmu.edu.tw)
  • Western blot was used for analysis of protein levels, Boyden chamber assays for analyses of cell migration and co-immunoprecipitation (CoIP) followed by western blot, PCR or qPCR for analysis of protein-protein and protein-mRNA interactions. (biomedcentral.com)
  • CSN2 knockdown led to a reduction of both CSN5 protein and mRNA whilst CSN5 knockdown had little effect on CSN2. (biomedcentral.com)
  • Drosophila Jumonji/Jarid2 (dJmj) has been identified as a component of Polycomb repressive complex 2. (sdbonline.org)
  • Upon T-cell receptor (TCR)-mediated T-cell activation, deubiquitinates 'Lys-63'-polyubiquitin chains on MALT1 thereby mediating disassociation of the CBM (CARD11:BCL10:MALT1) and IKK complexes and preventing sustained IKK activation. (icr.ac.uk)
  • Due to the tumour-suppressive function of PP2A acting as an antagonist of protein kinases this may be relevant for the anti-tumour effects of metformin [ 16 , 17 ]. (biomedcentral.com)
  • Protein kinases have become one of the most important target classes for the development of more effective anticancer drugs. (cisbio.net)
  • Each PROTAC molecule can seek out and destroy many protein molecules in its lifetime. (cisbio.net)
  • Each PROTAC consists of a linker with a ligand on one end to confer target specificity, and a different ligand on the other end to engage the cell's ubiquitin system. (cisbio.net)
  • The PROTAC thus acts as a bridge that brings the target of interest into close proximity with an E3 ubiquitin ligase (Fig 1). (cisbio.net)
  • Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. (embl-heidelberg.de)
  • Our data present the first evidence for the sequential loss of F-box proteins upon CSN manipulation and are the first to identify a potential link between CSN function and autophagy. (biomedcentral.com)
  • Evidence suggests that RBR proteins are often parts of cullin-containing ubiquitin ligase complexes. (embl.de)
  • Our results define TMEM127 as a component of the ubiquitin system and identify aberrant RET stabilization as a likely mechanism through which TMEM127 loss-of-function mutations cause pheochromocytoma. (stanford.edu)
  • This review describes recent advances in the role of human HMGB proteins and other proteins interacting with them, in cancerous processes related to oxidative stress, with special reference to ovarian and prostate cancer. (hindawi.com)
  • Today's precision molecular therapies are dramatically improving outcomes for patients suffering from complex diseases such as cancer. (cisbio.net)
  • HMGB1 is an abundant protein, 10 6 molecules per cell [ 7 ], which has been postulated as a redox sensor [ 8 ]. (hindawi.com)
  • Many mechanistic features and protein constituents are still ill defined. (tcdb.org)