• Here, the authors identify pevonedistat, NEDD8 inhibitor, as synergistic with irinotecan by blocking neddylation-activated ubiquitin/proteasomal degradation of TOP1-DPC. (nature.com)
  • Cell-fate-determinant molecule NUMB-interacting protein (TBC1D15) is overexpressed and contributes to p53 degradation in TICs. (nature.com)
  • Mutations in the CUL7 gene, including the Gln1553Ter mutation, prevent the cullin-7 protein from bringing together the components of the E3 ubiquitin ligase complex, interfering with the process of tagging unneeded proteins for degradation. (medlineplus.gov)
  • Specifically, cullin-7 helps assemble a complex called an E3 ubiquitin ligase, which tags the unneeded proteins for degradation. (medlineplus.gov)
  • In particular, ubiquitin-mediated degradation is critically important at transition points where it provides directionality and irreversibility to the cell cycle, which is essential for maintaining genome integrity. (intechopen.com)
  • Ubiquitination of AURKB by BCR(KLHL21) E3 ubiquitin ligase complex may not lead to its degradation by the proteasome. (ucsc.edu)
  • Proteasome inhibitors MG132 or PS-341 and lysosome inhibitor Chloroquine (CQ) were used to inhibit proteasomal or lysosomal-mediated protein degradation respectively. (biomedcentral.com)
  • During growth, genes associated with protein ubiquitination/deubiquitination, cell cycle progression, and proteasomal degradation were affected, while genes linked to protein and carbohydrate catabolism were affected during early development. (frontiersin.org)
  • however, the encoded protein is a component of a multiprotein E3 ubiquitin ligase complex that mediates the targeting of substrate proteins for proteasomal degradation. (thermofisher.com)
  • 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)
  • Cyclin F, encoded by CCNF, is the substrate recognition component of the Skp1-Cul1-F-box E3 ubiquitin ligase complex, SCF cyclin F . E3 ubiquitin ligases play a key role in ubiquitin-proteasome mediated protein degradation, an essential component of protein homeostatic mechanisms within the cell. (edu.au)
  • Both ubiquitylated Ho and Ufo1 are transferred by the UbL-UbA protein, Ddi1, to the 19S Regulatory Particle (RP) of the proteasome for degradation. (bvsalud.org)
  • The Ddi1-UbL domain binds Rpn1 of the 19S RP, the Ddi1-UbA domain binds ubiquitin chains on the degradation substrate. (bvsalud.org)
  • The substrate-shield model predicts that Ho would protect Ufo1 from degradation and we find that Ddi1 binds Ho, Ufo1, and Rpn1 simultaneously forming a complex for transfer of Ho to the 19S RP. (bvsalud.org)
  • This would promote degradation of Ufo1 and disassembly of SCF(Ufo1) complexes. (bvsalud.org)
  • Cd did not affect the protein levels of Keap1, which is a repressor of the cytoplasmic Nrf2, or Cul-3, an E3 ligase involved in the proteasomal degradation of Nrf2. (cdc.gov)
  • In the largest E3 ligase subfamily, Cul3 binds a BTB domain, and an associated protein-interaction domain such as MATH recruits substrates for ubiquitination. (rcsb.org)
  • N-Terminally extended human ubiquitin-conjugating enzymes (E2s) mediate the ubiquitination of RING-finger proteins, ARA54 and RNF8. (nih.gov)
  • Numerous E3 ubiquitin ligases, which facilitate the ubiquitination of specific substrates, have been shown to control G1/S. In this chapter, we will discuss components in the ubiquitin proteasome system that are implicated in G1/S control, how these enzymes are interconnected, gaps in our current knowledge, and the potential role of these pathways in the cancer cycle and disease proliferation. (intechopen.com)
  • The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB. (ucsc.edu)
  • protein ubiquitination. (ucsc.edu)
  • Cadmium coordinates up-regulation of cytoprotective genes and protection agains metal toxicity by inhibiting the ubiquitination of Nrf2 and disrupting the Nrf2/Keap1 complex. (cdc.gov)
  • Cd stabilized the Nrf2 protein by inhibiting the Keap1/CuI3dependent ubiquitination and 26S proteasomal turnover of Nrf2. (cdc.gov)
  • Cd treatment reduced the ubiquitination of Nrf2, increased the nuclear accumulation of Nrf2, and disrupted the Nrf2/Keap1 complex in the nucleus. (cdc.gov)
  • In particular, the proteins produced from the genes associated with 3-M syndrome are thought to help regulate proteins involved in the body's response to growth hormones, although their specific role in this process is unknown. (medlineplus.gov)
  • The multifunctional regulator nuclear factor erythroid 2-related factor (Nrf2) is considered not only as a cytoprotective factor regulating the expression of genes coding for anti-oxidant, anti-inflammatory and detoxifying proteins, but it is also a powerful modulator of species longevity. (springer.com)
  • The major characteristics of Nrf2 are to some extent mimicked by Nrf2-dependent genes and their proteins including heme oxygenase-1 (HO-1), which besides removing toxic heme, produces biliverdin, iron ions and carbon monoxide. (springer.com)
  • The discovery of the antioxidant response element (ARE) have led to the conclusion that the battery of genes, including glutamate-cysteine ligase (GCL), thioredoxin reductase 1 (Txnrd1), NAD(P)H-quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HMOX1) is regulated through Nrf2 binding to this consensus binding sequence [ 3 ]. (springer.com)
  • Extensive evidence has revealed that the core clock machinery involves "clock genes" and "clock proteins" functioning as molecular cogs. (bioone.org)
  • Overall, this study reveals the impact of cln5 -deficiency on gene expression in D. discoideum , provides insight on the genes and proteins that play a role in regulating Cln5-dependent processes, and sheds light on the molecular mechanisms underlying CLN5 disease. (frontiersin.org)
  • Over two dozen proteins involved in protein import and membrane insertion, peroxins, encoded by PEX genes, have been characterized. (tcdb.org)
  • Transcription factor Nrf2 is a key regulator of genes encoding phase II detoxification enzymes and antioxidant proteins in response to environmental chemical insults. (cdc.gov)
  • Contributes to ubiquitin-protein transferase activity. (nih.gov)
  • This system also regulates the level of proteins involved in several critical cell activities such as the timing of cell division and growth. (medlineplus.gov)
  • Here, we report that PSMA is localized to a membrane compartment in the vicinity of mitotic spindle poles and associates with the anaphase-promoting complex (APC). (nih.gov)
  • SPB association of Plo1 requires mitosis-promoting factor (MPF) activity, whereas its disassociation requires the activity of the anaphase-promoting complex. (kent.ac.uk)
  • Mechanistic studies indicate that the regulatory role of TRIM28 on MAGEC2 protein expression in tumor cells depends on proteasome-mediated pathway. (biomedcentral.com)
  • However, like most CLN proteins, the association of CLN5 with a defined biological pathway is still under investigation. (frontiersin.org)
  • The vast majority of proteins entering the secretory pathway are synthesized on ribosomes docked at ER translocons and are co-transationally translocated into the ER lumen. (stanford.edu)
  • This highly complex 'protein biogenesis' process is assisted by a diverse network of folding catalysts and protein-modifying enzymes and is scrutinized by molecular chaperones and other 'quality control' factors which ensure that only correctly folded and assembled proteins exit the ER and proceed to distal compartments of the secretory pathway. (stanford.edu)
  • Our goal is to elucidate the functional networks that coordinate protein synthesis and quality control in the early secretory pathway. (stanford.edu)
  • UBE3A is associated with cervical cancer and may combine with the E6 proto-oncogene encoded by HPV16 within cervical cancer cells to form the E6/E6-AP protein complex through the ubiquitin proteasome pathway ( 4 ). (spandidos-publications.com)
  • In addition, numerous important cellular proteins, such as B-cell lymphoma-2 homologous antagonist/killer, Myc proto-oncogene protein, cyclin-dependent kinase inhibitor 1B, DNA replication licensing factor MCM-7, retinoblastoma 1 and Annexin A1, are degenerated through the UBE3A-mediated ubiquitin proteasome pathway ( 7 ). (spandidos-publications.com)
  • Under homeostatic conditions, Nrf2 is rapidly degradated through a Keap1-dependent, ubiquitin-26S proteasome pathway. (cdc.gov)
  • The Constant region is proximal to the cell membrane, followed by a transmembrane region and a short cytoplasmic tail, while the Variable region binds to the peptide/MHC complex. (wikipedia.org)
  • Our interpretation is that in the absence of substrate, the Ddi1-UbL binds Rpn1 while the Ddi1-UbA binds ubiquitin chains on Ufo1. (bvsalud.org)
  • Pex4p is a membrane protein that may facilitate cycling of Pex5p back to the cytosol. (tcdb.org)
  • Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for efficient chromosome alignment and cytokinesis. (ucsc.edu)
  • The complex also contains other proteins that may confer substrate specificity on the complex. (planteome.org)
  • C-terminal PTS1 [(SAC)-(KRH)-(LM)] and N-terminal PTS2 [(RK)-(LIV)-X 5 -(HQ)-(LA)] targeting sequences are recognized by Pex5p and Pex7p, respectively, which may shuttle with the substrate protein to the peroxisomal lumen. (tcdb.org)
  • The accumulation of both Cyclin and CKI proteins is tightly regulated at the level of transcription. (intechopen.com)
  • In addition, Cyclin and CKI proteins are controlled at the level of their destruction. (intechopen.com)
  • By recognising and regulating the availability of several protein substrates, SCF cyclin F plays a role in regulating various cellular processes including replication and repair of DNA and cell cycle checkpoint control. (edu.au)
  • The overexpression of miRNA‑375 significantly increased caspase‑3 and caspase‑9 activities, induced B‑cell lymphoma 2 (Bcl‑2)/Bcl‑2‑associated X protein, tumor protein 53 and cyclin‑dependent kinase inhibitor 1 protein expression and suppressed cyclin D1 and survivin protein expression in HPV‑18(+) cervical cancer cells. (spandidos-publications.com)
  • One feature of nuclear organization is the existence of subcompartments in which specific DNA sequences and proteins associate creating microenvironments that can be more or less favorable for specific processes. (cea.fr)
  • In mammals, mutation of proteins involved in the nuclear architecture (lamins and lamin associated proteins) results in diseases associated with genomic instability. (cea.fr)
  • Intrinsically disordered regions in Pex13 and Pex5 resemble those found in nuclear pore complex proteins. (tcdb.org)
  • Furthermore, GSOs protected cells against GLU-induced apoptosis by reducing the expression of the mitochondrial apoptosis-associated Bcl-2 family effector proteins and protected cells from GLU-induced oxidative damage by increasing the nuclear translocation of Nrf2 and HO-1 expression. (sdbonline.org)
  • Most of these mutations substitute one protein building block (amino acid) for another amino acid in the cullin-7 protein or result in a cullin-7 protein that is abnormally short and nonfunctional. (medlineplus.gov)
  • Cancer is a complex genetic disease caused by abnormal alteration (mutations) in DNA sequences that leads to dyregulation of normal cellular processes thereby driving tumor growth. (intechopen.com)
  • Mutations in RAS proteins initiate many of the most aggressive tumors, and the search for pharmacological inhibitors of these proteins has become a priority in the battle against cancer. (news-medical.net)
  • Proto-Oncogene Proteins c-mdm2" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (umassmed.edu)
  • This graph shows the total number of publications written about "Proto-Oncogene Proteins c-mdm2" by people in this website by year, and whether "Proto-Oncogene Proteins c-mdm2" was a major or minor topic of these publications. (umassmed.edu)
  • Below are the most recent publications written about "Proto-Oncogene Proteins c-mdm2" by people in Profiles. (umassmed.edu)
  • Membrane proteins must be threaded co-translocationally into the lipid bilayer to become membrane-integrated, often with complex topologies and typically form hetero- or homo- oligomers. (stanford.edu)
  • The CUL7 gene provides instructions for making a protein called cullin-7. (medlineplus.gov)
  • In particular, cullin-7 is thought to help regulate proteins involved in the body's response to growth hormones, although its specific role in this process is unknown. (medlineplus.gov)
  • This mutation replaces the amino acid glutamine with a premature stop signal in the instructions for making the cullin-7 protein (written as Gln1553Ter or Q1553X), leading to production of an abnormally short protein. (medlineplus.gov)
  • The cullin-7 protein plays a role in the cell machinery that breaks down (degrades) unwanted proteins, called the ubiquitin-proteasome system. (medlineplus.gov)
  • The protein produced from the OBSL1 gene is thought to help maintain normal levels of cullin-7. (medlineplus.gov)
  • Evidence suggests that RBR proteins are often parts of cullin-containing ubiquitin ligase complexes. (embl.de)
  • Its ability to ubiquitinate p53 is regulated by TUMOR SUPPRESSOR PROTEIN P14ARF. (umassmed.edu)
  • The expression level of MAGEC2 protein was significantly reduced when TRIM28 was depleted in tumor cells, and no changes were observed in MAGEC2 mRNA level. (biomedcentral.com)
  • In this study, we found that expression of MAGEC2 protein in tumor cells depends on the expression of TRIM28, a reduction in the level of endogenous TRIM28 expression in melanoma cells resulting in significantly decreased expression of MAGEC2 protein. (biomedcentral.com)
  • Each configuration contains a contact zone, consisting of the set of amino acids from both interacting proteins that are with interaction distance, usually spanning from 3 to 5 Ångströms. (biomedcentral.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)
  • 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)
  • 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)
  • Both proteins were ubiquitinated in the cytoplasm. (cdc.gov)
  • Plant sequencesincluded the pathogenesis-related proteins 10, the major latexproteins/ripening-related proteins subfamily, and polyketide cyclase-likesequences. (embl.de)
  • Nrf2 consists of six functional Neh domains (Neh1-Neh6), from which, the amino-terminal Neh2 domain controls binding Keap1-the inhibitor protein Kelch-like ECH-associated protein 1, that is responsible for the cytosolic sequestration of Nrf2 under physiological conditions (Fig. 2 a). (springer.com)
  • It seems now clear that posttranslational modification of both DNA repair and checkpoint proteins is of importance for the regulation of their activities but how these modifications are regulated and how they affect the activity of the proteins only begins to be described. (cea.fr)
  • We propose a model in which association of NHR-67 with the Groucho/TCF complex suppresses the default invasive state in non-invasive cells, which complements transcriptional regulation to add robustness to the proliferative-invasive cellular switch in vivo . (elifesciences.org)
  • Orthologous to human RNF14 (ring finger protein 14). (nih.gov)
  • 2011 ) have reviewed the processes by which matrix and membrane proteins are incorporated into the peroxysome. (tcdb.org)
  • 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)
  • 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)
  • The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. (wikipedia.org)
  • TRIADs: a new class of proteins with a novel cysteine-rich signature. (nih.gov)
  • and ubiquitin protein ligase activity. (nih.gov)
  • Enables identical protein binding activity and small GTPase binding activity. (nih.gov)
  • The activity of CDKs is controlled by their binding to coactivator subunits termed Cyclins, as well as by CDK inhibitory proteins termed CKIs. (intechopen.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)
  • A protein complex that includes a ubiquitin-protein ligase and enables ubiquitin protein ligase activity. (planteome.org)
  • Ubiquitin Proteasome System Current Insights into Mechanism Cellular Regu. (intechopen.com)
  • The TCR is a disulfide-linked membrane-anchored heterodimeric protein normally consisting of the highly variable alpha (α) and beta (β) chains expressed as part of a complex with the invariant CD3 chain molecules. (wikipedia.org)
  • This complex tags damaged and excess proteins with molecules called ubiquitin. (medlineplus.gov)
  • HMGB1 is an abundant protein, 10 6 molecules per cell [ 7 ], which has been postulated as a redox sensor [ 8 ]. (hindawi.com)
  • citation needed] The residues in these variable domains are located in two regions of the TCR, at the interface of the α- and β-chains and in the β-chain framework region that is thought to be in proximity to the CD3 signal-transduction complex. (wikipedia.org)
  • Mathematical modeling of signal transduction networks has previously been used to map out thermodynamical using rate equations is increasingly attracting attention as a properties of protein-folding models (6,7). (lu.se)
  • 13-15 Ψ plays an important role in various aspects of RNA biology, and, therefore, participates in many biological process, including translational control, 16 , 17 RNA folding, 18-22 protein translation, 23-26 and clinical diseases. (haematologica.org)
  • Repair of topoisomerase 1 (TOP1) DNA protein crosslinks (DPC) limits the efficacy of the TOP1 inhibitor irinotecan in cancer therapy. (nature.com)
  • Keap1 is a cysteine-rich protein, known to be anchored to actin cytoskeleton [ 5 ], serving as an adaptor protein for the Cul3-dependent E3 ubiquitin ligase complex. (springer.com)
  • Dystrophin-glycoprotein complex bridges the inner cytoskeleton (F-actin) and the basal lamina. (medscape.com)
  • 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)
  • Ubiquitin serves as a signal to specialized cell structures known as proteasomes, which attach (bind) to the tagged proteins and degrade them. (medlineplus.gov)
  • Prostate-specific membrane antigen (PSMA) is a transmembrane protein highly expressed in advanced and metastatic prostate cancers. (nih.gov)
  • A large pore is formed by transmembrane proteins. (tcdb.org)
  • These studies provide a molecular understanding of how MATH-BTB proteins recruit substrates to Cul3 and how their dimerization and conformational variability may facilitate avid interactions with diverse substrates. (rcsb.org)
  • Basic sequence-derived (length, molecular weight, isoelectric point) and experimentally-determined (median abundance, median absolute deviation) protein information. (yeastgenome.org)
  • The TCR is composed of two different protein chains (that is, it is a heterodimer). (wikipedia.org)
  • Synthetic peptide taken within amino acid region 390-440 on human Parkin protein. (thermofisher.com)
  • To study the potential role in this metabolic shift of von Hippel-Lindau (VHL), a protein component of a ubiquitin ligase complex, the authors generated nephron progenitor cell-specific VHL knockout mice. (lww.com)
  • They were classified into elevenfamilies, five of which were newly identified and not included in theStructural Classification of Proteins database release 1.71. (embl.de)
  • A distance-based phylogenetic treeyielded a classification into 11 subfamilies, nine exclusively containingplant sequences and two subfamilies of bacterial proteins. (embl.de)
  • This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. (embl.de)
  • Download DNA or protein sequence, view genomic context and coordinates. (yeastgenome.org)
  • Click "Protein Details" for further information about the protein such as half-life, abundance, domains, domains shared with other proteins, protein sequence retrieval for various strains, physico-chemical properties, protein modification sites, and external identifiers for the protein. (yeastgenome.org)
  • We further demonstrate a role for the E3 ligase MARCH6 in regulating triacylglycerol biosynthesis, thereby influencing LD abundance and PLIN2 stability. (stanford.edu)