A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes.
A class of enzymes that catalyze the formation of a bond between two substrate molecules, coupled with the hydrolysis of a pyrophosphate bond in ATP or a similar energy donor. (Dorland, 28th ed) EC 6.
A highly conserved 76-amino acid peptide universally found in eukaryotic cells that functions as a marker for intracellular PROTEIN TRANSPORT and degradation. Ubiquitin becomes activated through a series of complicated steps and forms an isopeptide bond to lysine residues of specific proteins within the cell. These "ubiquitinated" proteins can be recognized and degraded by proteosomes or be transported to specific compartments within the cell.
A family of proteins that are structurally-related to Ubiquitin. Ubiquitins and ubiquitin-like proteins participate in diverse cellular functions, such as protein degradation and HEAT-SHOCK RESPONSE, by conjugation to other proteins.
A syndrome characterized by multiple abnormalities, MENTAL RETARDATION, and movement disorders. Present usually are skull and other abnormalities, frequent infantile spasms (SPASMS, INFANTILE); easily provoked and prolonged paroxysms of laughter (hence "happy"); jerky puppetlike movements (hence "puppet"); continuous tongue protrusion; motor retardation; ATAXIA; MUSCLE HYPOTONIA; and a peculiar facies. It is associated with maternal deletions of chromosome 15q11-13 and other genetic abnormalities. (From Am J Med Genet 1998 Dec 4;80(4):385-90; Hum Mol Genet 1999 Jan;8(1):129-35)
A class of enzymes that form a thioester bond to UBIQUITIN with the assistance of UBIQUITIN-ACTIVATING ENZYMES. They transfer ubiquitin to the LYSINE of a substrate protein with the assistance of UBIQUITIN-PROTEIN LIGASES.
Complexes of enzymes that catalyze the covalent attachment of UBIQUITIN to other proteins by forming a peptide bond between the C-terminal GLYCINE of UBIQUITIN and the alpha-amino groups of LYSINE residues in the protein. The complexes play an important role in mediating the selective-degradation of short-lived and abnormal proteins. The complex of enzymes can be broken down into three components that involve activation of ubiquitin (UBIQUITIN-ACTIVATING ENZYMES), conjugation of ubiquitin to the ligase complex (UBIQUITIN-CONJUGATING ENZYMES), and ligation of ubiquitin to the substrate protein (UBIQUITIN-PROTEIN LIGASES).
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.
A set of protein subcomplexes involved in PROTEIN SORTING of UBIQUITINATED PROTEINS into intraluminal vesicles of MULTIVESICULAR BODIES and in membrane scission during formation of intraluminal vesicles, during the final step of CYTOKINESIS, and during the budding of enveloped viruses. The ESCRT machinery is comprised of the protein products of Class E vacuolar protein sorting genes.
A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.
A family of structurally related proteins that were originally discovered for their role in cell-cycle regulation in CAENORHABDITIS ELEGANS. They play important roles in regulation of the CELL CYCLE and as components of UBIQUITIN-PROTEIN LIGASES.
An E3 ubiquitin ligase primarily involved in regulation of the metaphase-to-anaphase transition during MITOSIS through ubiquitination of specific CELL CYCLE PROTEINS. Enzyme activity is tightly regulated through subunits and cofactors, which modulate activation, inhibition, and substrate specificity. The anaphase-promoting complex, or APC-C, is also involved in tissue differentiation in the PLACENTA, CRYSTALLINE LENS, and SKELETAL MUSCLE, and in regulation of postmitotic NEURONAL PLASTICITY and excitability.
A subset of ubiquitin protein ligases that are formed by the association of a SKP DOMAIN PROTEIN, a CULLIN DOMAIN PROTEIN and a F-BOX DOMAIN PROTEIN.
Enzymes that catalyze the joining of two molecules by the formation of a carbon-nitrogen bond. EC 6.3.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A family of proteins that share the F-BOX MOTIF and are involved in protein-protein interactions. They play an important role in process of protein ubiquition by associating with a variety of substrates and then associating into SCF UBIQUITIN LIGASE complexes. They are held in the ubiquitin-ligase complex via binding to SKP DOMAIN PROTEINS.
An oligomer formed from the repetitive linking of the C-terminal glycine of one UBIQUITIN molecule via an isopeptide bond to a lysine residue on a second ubiquitin molecule. It is structurally distinct from UBIQUITIN C, which is a single protein containing a tandemly arrayed ubiquitin peptide sequence.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A class of enzymes that catalyzes the ATP-dependent formation of a thioester bond between itself and UBIQUITIN. It then transfers the activated ubiquitin to one of the UBIQUITIN-PROTEIN LIGASES.
The form of fatty acid synthase complex found in BACTERIA; FUNGI; and PLANTS. Catalytic steps are like the animal form but the protein structure is different with dissociated enzymes encoded by separate genes. It is a target of some ANTI-INFECTIVE AGENTS which result in disruption of the CELL MEMBRANE and CELL WALL.
A family of structurally-related proteins that were originally identified by their ability to complex with cyclin proteins (CYCLINS). They share a common domain that binds specifically to F-BOX MOTIFS. They take part in SKP CULLIN F-BOX PROTEIN LIGASES, where they can bind to a variety of F-BOX PROTEINS.
Incorporation of biotinyl groups into molecules.
An enzyme that catalyzes the conversion of linear RNA to a circular form by the transfer of the 5'-phosphate to the 3'-hydroxyl terminus. It also catalyzes the covalent joining of two polyribonucleotides in phosphodiester linkage. EC 6.5.1.3.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
A thioester hydrolase which acts on esters formed between thiols such as DITHIOTHREITOL or GLUTATHIONE and the C-terminal glycine residue of UBIQUITIN.
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
A family of F-box domain proteins that contain sequences that are homologous to the beta subunit of transducin (BETA-TRANSDUCIN). 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.
A water-soluble, enzyme co-factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Established cell cultures that have the potential to propagate indefinitely.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Protein structural motifs that play a role in protein-protein binding. The motifs are comprised of approximately 50 residues. Their name derives from the fact that they were found in cyclin F.
Ligases that catalyze the joining of adjacent AMINO ACIDS by the formation of carbon-nitrogen bonds between their carboxylic acid groups and amine groups.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.
An octanoic acid bridged with two sulfurs so that it is sometimes also called a pentanoic acid in some naming schemes. It is biosynthesized by cleavage of LINOLEIC ACID and is a coenzyme of oxoglutarate dehydrogenase (KETOGLUTARATE DEHYDROGENASE COMPLEX). It is used in DIETARY SUPPLEMENTS.
Transport proteins that carry specific substances in the blood or across cell membranes.
ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
Systems of enzymes which function sequentially by catalyzing consecutive reactions linked by common metabolic intermediates. They may involve simply a transfer of water molecules or hydrogen atoms and may be associated with large supramolecular structures such as MITOCHONDRIA or RIBOSOMES.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
A carboxylating enzyme that catalyzes the conversion of ATP, acetyl-CoA, and HCO3- to ADP, orthophosphate, and malonyl-CoA. It is a biotinyl-protein that also catalyzes transcarboxylation. The plant enzyme also carboxylates propanoyl-CoA and butanoyl-CoA (From Enzyme Nomenclature, 1992) EC 6.4.1.2.
Poly(deoxyribonucleotide):poly(deoxyribonucleotide)ligases. Enzymes that catalyze the joining of preformed deoxyribonucleotides in phosphodiester linkage during genetic processes during repair of a single-stranded break in duplex DNA. The class includes both EC 6.5.1.1 (ATP) and EC 6.5.1.2 (NAD).
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
A group of compounds with the general formula M10(PO4)6(OH)2, where M is barium, strontium, or calcium. The compounds are the principal mineral in phosphorite deposits, biological tissue, human bones, and teeth. They are also used as an anticaking agent and polymer catalysts. (Grant & Hackh's Chemical Dictionary, 5th ed)
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Macromolecular complexes formed from the association of defined protein subunits.
A ubiquitin-protein ligase that mediates OXYGEN-dependent polyubiquitination of HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT. It is inactivated in VON HIPPEL-LINDAU SYNDROME.
A conserved class of proteins that control APOPTOSIS in both VERTEBRATES and INVERTEBRATES. IAP proteins interact with and inhibit CASPASES, and they function as ANTI-APOPTOTIC PROTEINS. The protein class is defined by an approximately 80-amino acid motif called the baculoviral inhibitor of apoptosis repeat.
Proteins transcribed from the E4 region of ADENOVIRUSES. The E4 19K protein transactivates transcription of the adenovirus E2F protein and complexes with it.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
A zinc-binding domain defined by the sequence Cysteine-X2-Cysteine-X(9-39)-Cysteine-X(l-3)-His-X(2-3)-Cysteine-X2-Cysteine -X(4-48)-Cysteine-X2-Cysteine, where X is any amino acid. The RING finger motif binds two atoms of zinc, with each zinc atom ligated tetrahedrally by either four cysteines or three cysteines and a histidine. The motif also forms into a unitary structure with a central cross-brace region and is found in many proteins that are involved in protein-protein interactions. The acronym RING stands for Really Interesting New Gene.
Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.
Catalyze the joining of preformed ribonucleotides or deoxyribonucleotides in phosphodiester linkage during genetic processes. EC 6.5.1.
The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.
Proteins prepared by recombinant DNA technology.
A single protein comprised of tandem repeats of the UBIQUITIN 78-amino acid sequence. It is a product of the polyubiquitin gene which contains multiple copies of the ubiquitin coding sequence. Proteolytic processing of ubiquitin C results in the formation of individual ubiquitin molecules. This protein is distinct from POLYUBIQUITIN, which is a protein formed through isopeptide linkage of multiple ubiquitin species.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Proteins encoded by the VIF GENES of the HUMAN IMMUNODEFICIENCY VIRUS.
Proteins found in any species of bacterium.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
Proto-oncogene proteins that negatively regulate RECEPTOR PROTEIN-TYROSINE KINASE signaling. It is a UBIQUITIN-PROTEIN LIGASE and the cellular homologue of ONCOGENE PROTEIN V-CBL.
One of the enzymes active in the gamma-glutamyl cycle. It catalyzes the synthesis of gamma-glutamylcysteine from glutamate and cysteine in the presence of ATP with the formation of ADP and orthophosphate. EC 6.3.2.2.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
Proteins obtained from ESCHERICHIA COLI.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
A heterogeneous group of disorders characterized by renal electrolyte transport dysfunctions. Congenital forms are rare autosomal disorders characterized by neonatal hypertension, HYPERKALEMIA, increased RENIN activity and ALDOSTERONE concentration. The Type I features HYPERKALEMIA with sodium wasting; Type II, HYPERKALEMIA without sodium wasting. Pseudohypoaldosteronism can be the result of a defective renal electrolyte transport protein or acquired after KIDNEY TRANSPLANTATION.
A group of cell cycle proteins that negatively regulate the activity of CYCLIN/CYCLIN-DEPENDENT KINASE complexes. They inhibit CELL CYCLE progression and help control CELL PROLIFERATION following GENOTOXIC STRESS as well as during CELL DIFFERENTIATION.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
A family of structurally related proteins that are induced by CYTOKINES and negatively regulate cytokine-mediated SIGNAL TRANSDUCTION PATHWAYS. SOCS proteins contain a central SH2 DOMAIN and a C-terminal region of homology known as the SOCS box.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
A cell line derived from cultured tumor cells.
Protein motif that contains a 33-amino acid long sequence that often occurs in tandem arrays. This repeating sequence of 33-amino acids was discovered in ANKYRIN where it is involved in interaction with the anion exchanger (ANION EXCHANGE PROTEIN 1, ERYTHROCYTE). Ankyrin repeats cooperatively fold into domains that mediate molecular recognition via protein-protein interactions.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
Proteins transcribed from the E1B region of ADENOVIRUSES which are involved in regulation of the levels of early and late viral gene expression.
Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.
An essential amino acid. It is often added to animal feed.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Proteins covalently modified with UBIQUITINS or UBIQUITIN-LIKE PROTEINS.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A 1.5-kDa small ubiquitin-related modifier protein that can covalently bind via an isopeptide link to a number of cellular proteins. It may play a role in intracellular protein transport and a number of other cellular processes.
A DNA amplification technique based upon the ligation of OLIGONUCLEOTIDE PROBES. The probes are designed to exactly match two adjacent sequences of a specific target DNA. The chain reaction is repeated in three steps in the presence of excess probe: (1) heat denaturation of double-stranded DNA, (2) annealing of probes to target DNA, and (3) joining of the probes by thermostable DNA ligase. After the reaction is repeated for 20-30 cycles the production of ligated probe is measured.
A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
Members of the peptidase C19 family which regulate signal transduction by removing UBIQUITIN from specific protein substrates via a process known as deubiquitination or deubiquitylation.
Proteins synthesized by HUMAN IMMUNODEFICIENCY VIRUSES such as the HIV-1 and HIV-2.
A basic-leucine zipper transcription factor that was originally described as a transcriptional regulator controlling expression of the BETA-GLOBIN gene. It may regulate the expression of a wide variety of genes that play a role in protecting cells from oxidative damage.
Proteins that originate from plants species belonging to the genus ARABIDOPSIS. The most intensely studied species of Arabidopsis, Arabidopsis thaliana, is commonly used in laboratory experiments.
The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.
CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)
A broad category of viral proteins that play indirect roles in the biological processes and activities of viruses. Included here are proteins that either regulate the expression of viral genes or are involved in modifying host cell functions. Many of the proteins in this category serve multiple functions.
A non-DNA binding transcription factor that is a subunit of core binding factor. It forms heterodimeric complexes with CORE BINDING FACTOR ALPHA SUBUNITS, and regulates GENETIC TRANSCRIPTION of a variety of GENES involved primarily in CELL DIFFERENTIATION and CELL CYCLE progression.
A class of structurally related proteins of 12-20 kDa in size. They covalently modify specific proteins in a manner analogous to UBIQUITIN.
Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.
A type of POST-TRANSLATIONAL PROTEIN MODIFICATION by SMALL UBIQUITIN-RELATED MODIFIER PROTEINS (also known as SUMO proteins).
A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
Compounds that inhibit the function or proteolytic action of the PROTEASOME.
An E3 UBIQUITIN LIGASE that interacts with and inhibits TUMOR SUPPRESSOR PROTEIN P53. Its ability to ubiquitinate p53 is regulated by TUMOR SUPPRESSOR PROTEIN P14ARF.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A plant genus of the family BRASSICACEAE that contains ARABIDOPSIS PROTEINS and MADS DOMAIN PROTEINS. The species A. thaliana is used for experiments in classical plant genetics as well as molecular genetic studies in plant physiology, biochemistry, and development.
A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.
Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.
A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)
Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.
A group of acylated oligopeptides produced by Actinomycetes that function as protease inhibitors. They have been known to inhibit to varying degrees trypsin, plasmin, KALLIKREINS, papain and the cathepsins.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.
Enzymes that catalyze the cleavage of a carbon-nitrogen bond by means other than hydrolysis or oxidation. Subclasses are the AMMONIA-LYASES, the AMIDINE-LYASES, the amine-lyases, and other carbon-nitrogen lyases. EC 4.3.
Proteins found in any species of fungus.
A group of alicyclic hydrocarbons with the general formula R-C5H9.

Identification of determinants in E2 ubiquitin-conjugating enzymes required for hect E3 ubiquitin-protein ligase interaction. (1/1110)

Members of the hect domain protein family are characterized by sequence similarity of their C-terminal regions to the C terminus of E6-AP, an E3 ubiquitin-protein ligase. An essential intermediate step in E6-AP-dependent ubiquitination is the formation of a thioester complex between E6-AP and ubiquitin in the presence of distinct E2 ubiquitin-conjugating enzymes including human UbcH5, a member of the UBC4/UBC5 subfamily of E2s. Similarly, several hect domain proteins, including Saccharomyces cerevisiae RSP5, form ubiquitin thioester complexes, indicating that hect domain proteins in general have E3 activity. We show here, by the use of chimeric E2s generated between UbcH5 and other E2s, that a region of UbcH5 encompassing the catalytic site cysteine residue is critical for its ability to interact with E6-AP and RSP5. Of particular importance is a phenylalanine residue at position 62 of UbcH5 that is conserved among the members of the UBC4/UBC5 subfamily but is not present in any of the other known E2s, whereas the N-terminal 60 amino acids do not contribute significantly to the specificity of these interactions. The conservation of this phenylalanine residue throughout evolution underlines the importance of the ability to interact with hect domain proteins for the cellular function of UBC4/UBC5 subfamily members.  (+info)

Inhibitory phosphorylation of the APC regulator Hct1 is controlled by the kinase Cdc28 and the phosphatase Cdc14. (2/1110)

BACKGROUND: Exit from mitosis requires inactivation of mitotic cyclin-dependent kinases (CDKs). A key mechanism of CDK inactivation is ubiquitin-mediated cyclin proteolysis, which is triggered by the late mitotic activation of a ubiquitin ligase known as the anaphase-promoting complex (APC). Activation of the APC requires its association with substoichiometric activating subunits termed Cdc20 and Hct1 (also known as Cdh1). Here, we explore the molecular function and regulation of the APC regulatory subunit Hct1 in Saccharomyces cerevisiae. RESULTS: Recombinant Hct1 activated the cyclin-ubiquitin ligase activity of APC isolated from multiple cell cycle stages. APC isolated from cells arrested in G1, or in late mitosis due to the cdc14-1 mutation, was more responsive to Hct1 than APC isolated from other stages. We found that Hct1 was phosphorylated in vivo at multiple CDK consensus sites during cell cycle stages when activity of the cyclin-dependent kinase Cdc28 is high and APC activity is low. Purified Hct1 was phosphorylated in vitro at these sites by purified Cdc28-cyclin complexes, and phosphorylation abolished the ability of Hct1 to activate the APC in vitro. The phosphatase Cdc14, which is known to be required for APC activation in vivo, was able to reverse the effects of Cdc28 by catalyzing Hct1 dephosphorylation and activation. CONCLUSIONS: We conclude that Hct1 phosphorylation is a key regulatory mechanism in the control of cyclin destruction. Phosphorylation of Hct1 provides a mechanism by which Cdc28 blocks its own inactivation during S phase and early mitosis. Following anaphase, dephosphorylation of Hct1 by Cdc14 may help initiate cyclin destruction.  (+info)

The schizosaccharomyces pombe dim1(+) gene interacts with the anaphase-promoting complex or cyclosome (APC/C) component lid1(+) and is required for APC/C function. (3/1110)

The Schizosaccharomyces pombe dim1(+) gene is required for entry into mitosis and for chromosome segregation during mitosis. To further understand dim1p function, we undertook a synthetic lethal screen with the temperature-sensitive dim1-35 mutant and isolated lid (for lethal in dim1-35) mutants. Here, we describe the temperature-sensitive lid1-6 mutant. At the restrictive temperature of 36 degrees C, lid1-6 mutant cells arrest with a "cut" phenotype similar to that of cut4 and cut9 mutants. An epitope-tagged version of lid1p is a component of a multiprotein approximately 20S complex; the presence of lid1p in this complex depends upon functional cut9(+). lid1p-myc coimmunoprecipitates with several other proteins, including cut9p and nuc2p, and the presence of cut9p in a 20S complex depends upon the activity of lid1(+). Further, lid1(+) function is required for the multiubiquitination of cut2p, an anaphase-promoting complex or cyclosome (APC/C) target. Thus, lid1p is a component of the S. pombe APC/C. In dim1 mutants, the abundances of lid1p and the APC/C complex decline significantly, and the ubiquitination of an APC/C target is abolished. These data suggest that at least one role of dim1p is to maintain or establish the steady-state level of the APC/C.  (+info)

Reconstitution of G1 cyclin ubiquitination with complexes containing SCFGrr1 and Rbx1. (4/1110)

Control of cyclin levels is critical for proper cell cycle regulation. In yeast, the stability of the G1 cyclin Cln1 is controlled by phosphorylation-dependent ubiquitination. Here it is shown that this reaction can be reconstituted in vitro with an SCF E3 ubiquitin ligase complex. Phosphorylated Cln1 was ubiquitinated by SCF (Skp1-Cdc53-F-box protein) complexes containing the F-box protein Grr1, Rbx1, and the E2 Cdc34. Rbx1 promotes association of Cdc34 with Cdc53 and stimulates Cdc34 auto-ubiquitination in the context of Cdc53 or SCF complexes. Rbx1, which is also a component of the von Hippel-Lindau tumor suppressor complex, may define a previously unrecognized class of E3-associated proteins.  (+info)

ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity. (5/1110)

We have identified two highly conserved RING finger proteins, ROC1 and ROC2, that are homologous to APC11, a subunit of the anaphase-promoting complex. ROC1 and ROC2 commonly interact with all cullins while APC11 specifically interacts with APC2, a cullin-related APC subunit. YeastROC1 encodes an essential gene whose reduced expression resulted in multiple, elongated buds and accumulation of Sic1p and Cln2p. ROC1 and APC11 immunocomplexes can catalyze isopeptide ligations to form polyubiquitin chains in an E1- and E2-dependent manner. ROC1 mutations completely abolished their ligase activity without noticeable changes in associated proteins. Ubiquitination of phosphorylated I kappa B alpha can be catalyzed by the ROC1 immunocomplex in vitro. Hence, combinations of ROC/APC11 and cullin proteins proteins potentially constitute a wide variety of ubiquitin ligases.  (+info)

Characterization of the DOC1/APC10 subunit of the yeast and the human anaphase-promoting complex. (6/1110)

The anaphase-promoting complex/cyclosome (APC) is a ubiquitin-protein ligase whose activity is essential for progression through mitosis. The vertebrate APC is thought to be composed of 8 subunits, whereas in budding yeast several additional APC-associated proteins have been identified, including a 33-kDa protein called Doc1 or Apc10. Here, we show that Doc1/Apc10 is a subunit of the yeast APC throughout the cell cycle. Mutation of Doc1/Apc10 inactivates the APC without destabilizing the complex. An ortholog of Doc1/Apc10, which we call APC10, is associated with the APC in different vertebrates, including humans and frogs. Biochemical fractionation experiments and mass spectrometric analysis of a component of the purified human APC show that APC10 is a genuine APC subunit whose cellular levels or association with the APC are not cell cycle-regulated. We have further identified an APC10 homology region, which we propose to call the DOC domain, in several protein sequences that also contain either cullin or HECT domains. Cullins are present in several ubiquitination complexes including the APC, whereas HECT domains represent the catalytic core of a different type of ubiquitin-protein ligase. DOC domains may therefore be important for reactions catalyzed by several types of ubiquitin-protein ligases.  (+info)

Cyclin-dependent kinase and Cks/Suc1 interact with the proteasome in yeast to control proteolysis of M-phase targets. (7/1110)

Cell cycle-specific proteolysis is critical for proper execution of mitosis in all eukaryotes. Ubiquitination and subsequent proteolysis of the mitotic regulators Clb2 and Pds1 depend on the cyclosome/APC and the 26S proteasome. We report here that components of the cell cycle machinery in yeast, specifically the cell cycle regulatory cyclin-dependent kinase Cdc28 and a conserved associated protein Cks1/Suc1, interact genetically, physically, and functionally with components of the 26S proteasome. A mutation in Cdc28 (cdc28-1N) that interferes with Cks1 binding, or inactivation of Cks1 itself, confers stabilization of Clb2, the principal mitotic B-type cyclin in budding yeast. Surprisingly, Clb2-ubiquitination in vivo and in vitro is not affected by mutations in cks1, indicating that Cks1 is not essential for cyclosome/APC activity. However, mutant Cks1 proteins no longer physically interact with the proteasome, suggesting that Cks1 is required for some aspect of proteasome function during M-phase-specific proteolysis. We further provide evidence that Cks1 function is required for degradation of the anaphase inhibitor Pds1. Stabilization of Pds1 is partially responsible for the metaphase arrest phenotype of cks1 mutants because deletion of PDS1 partially relieves the metaphase block in these mutants.  (+info)

Sister chromatid separation and chromosome re-duplication are regulated by different mechanisms in response to spindle damage. (8/1110)

In yeast, anaphase entry depends on Pds1 proteolysis, while chromosome re-duplication in the subsequent S-phase involves degradation of mitotic cyclins such as Clb2. Sequential proteolysis of Pds1 and mitotic cyclins is mediated by the anaphase-promoting complex (APC). Lagging chromosomes or spindle damage are detected by surveillance mechanisms (checkpoints) which block anaphase onset, cytokinesis and DNA re-replication. Until now, the MAD and BUB genes implicated in this regulation were thought to function in a single pathway that blocks APC activity. We show that spindle damage blocks sister chromatid separation solely by inhibiting APCCdc20-dependent Pds1 proteolysis and that this process requires Mad2. Blocking APCCdh1-mediated Clb2 proteolysis and chromosome re-duplication does not require Mad2 but a different protein, Bub2. Our data imply that Mad1, Mad2, Mad3 and Bub1 regulate APCCdc20, whereas Bub2 regulates APCCdh1.  (+info)

Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin-protein ligase complex that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C is thought to confer substrate specificity and, in the presence of ubiquitin-conjugating E2 enzymes, it catalyzes the formation of protein-ubiquitin conjugates that are subsequently degraded by the 26S proteasome. In early mitosis, the APC/C is activated by CDC20 and targets securin PDS1, the B-type cyclin CLB5, and other anaphase inhibitory proteins for proteolysis, thereby triggering the separation of sister chromatids at the metaphase-to-anaphase transition. In late mitosis and in G1, degradation of CLB5 allows activation of the APC/C by CDH1, which is needed to destroy CDC20 and the B-type cyclin CLB2 to allow exit from mitosis and creating the low CDK state necessary for cytokinesis and for reforming prereplicative complexes in G1 prior to another round of replication.
Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin-protein ligase complex that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C is thought to confer substrate specificity and, in the presence of ubiquitin-conjugating E2 enzymes, it catalyzes the formation of protein-ubiquitin conjugates that are subsequently degraded by the 26S proteasome. In early mitosis, the APC/C is activated by CDC20 and targets securin PDS1, the B-type cyclin CLB5, and other anaphase inhibitory proteins for proteolysis, thereby triggering the separation of sister chromatids at the metaphase-to-anaphase transition. In late mitosis and in G1, degradation of CLB5 allows activation of the APC/C by CDH1, which is needed to destroy CDC20 and the B-type cyclin CLB2 to allow exit from mitosis and creating the low CDK state necessary for cytokinesis and for reforming prereplicative complexes in G1 prior to another round of replication.
The authors then turned to a yeast two-hybrid screen and identified DP-E2F-LIKE 1/E2Fe (DEL1) as the transcription factor that recruits MED16 to chromatin, which solidified the link between MED16 and endoreduplication. Indeed, DEL1 targets are known: the CELL CYCLE SWITCH 52 genes CCS52A1 and CCS52A2, encoding activators of the Anaphase Promoting Complex (APC)/Cyclosome, an E3 ubiquitin ligase complex that degrades cell cycle proteins. This offered a testable model: DEL1 would bind to the CCS52A1 and CCS52A2 promoters and draw Mediator (via its MED16 subunit) to chromatin and establish transcriptional repression. Left unchecked, CCS52A expression would promote APC/Cyclosome activity and result in additional rounds of DNA replication.. Using chromatin immunoprecipitation assays, the authors confirmed that DEL1 and MED16 associate with cis-elements within the CCS52A1 and CCS52A2 promoters. In the case of MED16, this association is dependent on the presence of DEL1, which is consistent with the ...
Promoting complex/cyclosome (APC/C) associates with cadherin 1 (CDH1), acting as a ubiquitin ligase to down-regulate GA . The APC/C DH1 complicated targets
BACKGROUND: The aggressive B-cell non-Hodgkin lymphomas diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) are characterised by a high proliferation rate. The anaphase-promoting complex/cyclosome (APC/C) and its co-activators Cdc20 and Cdh1 represent an important checkpoint in mitosis. Here, the role of the APC/C and its co-activators is examined in DLBCL and MCL.. METHODS: The expression and prognostic value of Cdc20 and Cdh1 was investigated using GEP data and immunohistochemistry. Moreover, the therapeutic potential of APC/C targeting was evaluated using the small-molecule inhibitor proTAME and the underlying mechanisms of action were investigated by western blot.. RESULTS: We demonstrated that Cdc20 is highly expressed in DLBCL and aggressive MCL, correlating with a poor prognosis in DLBCL. ProTAME induced a prolonged metaphase, resulting in accumulation of the APC/C-Cdc20 substrate cyclin B1, inactivation/degradation of Bcl-2 and Bcl-xL and caspase-dependent apoptosis. In ...
The anaphase-promoting complex/cyclosome (APC/C) is an ubiquitin ligase that functions during mitosis. Here we identify the transcriptional regulator, transcriptional intermediary factor 1γ, TIF1γ, as an APC/C-interacting protein that regulates APC/C function. TIF1γ is not a substrate for APC/C-dependent ubiquitylation but instead, associates specifically with the APC/C holoenzyme and Cdc20 to affect APC/C activity and progression through mitosis. RNA interference studies indicate that TIF1γ knockdown results in a specific reduction in APC/C ubiquitin ligase activity, the stabilization of APC/C substrates, and an increase in the time taken for cells to progress through mitosis from nuclear envelope breakdown to anaphase. TIF1γ knockdown cells are also characterized by the inappropriate presence of cyclin A at metaphase, and an increase in the number of cells that fail to undergo metaphase-to-anaphase transition. Expression of a small interfering RNA-resistant TIF1γ species relieves the ...
We found that APCCdh1 is inactivated during S phase, and its complete inactivation requires Clb5p. Both Ase1p and Cdc20p were degraded in late G1-arrested cells containing high levels of G1 CDK activity. Cdh1p was required for the degradation of both substrates. We also found that a fraction of Cdh1p was bound to the APC/C in late G1-arrested cells. Further, the S phase cyclin Clb5p was required for the normal timing of APCCdh1 inactivation. Thus, in a normal cell cycle the additive activities of G1 and S phase CDKs inactivate APCCdh1. These findings have two implications for the design of the yeast cell cycle. First, the key role for Clb5p in APCCdh1 inactivation suggests that Clb5p has an important role in enabling the expression of mitotic cyclins. This function was previously ascribed entirely to G1 cyclins. Second, because Clb5p is degraded by APCCdc20 our finding that yeast Cdc20p is an APCCdh1 substrate suggests that high APCCdh1 activity throughout G1 may help ensure that Clb5p can ...
Author: Schmidt, A. et al.; Genre: Journal Article; Published in Print: 2005-02-15; Keywords: cell cycle; anaphase-promoting complex/cyclosome; Xenopus; polo-like kinase; cytostatic factor; mitotic exit; Title: Xenopus polo-like kinase Plx1 regulates XErp1, a novel inhibitor of APC/C activity
Well-timed protein degradation is a common event in the cell cycle, known to drive mitotic entry (G2/M) as well as the metaphase-to-anaphase transition (Teixeira and Reed, 2013; Bassermann et al., 2014). A frequent general question in these and other cell cycle processes is what defines the functional time window of an E3 ligase. In principle, either the activity of the E3 ligase may itself be regulated, or the substrate binding to the E3 ligase may depend on third-party factors such as kinases or scaffolding proteins. Mitosis provides a remarkable example of how an E3 ligase can be dynamically regulated, in this case to tightly coordinate the status of kinetochore-microtubule attachments with the onset of chromosome separation. It is long known that the metaphase-to-anaphase transition is driven by the E3 ligase anaphase-promoting complex/cyclosome (APC/C; see Cullin-RING and APC/C E3 ligases text box), activated by its subunit CDC20 (Teixeira and Reed, 2013; Bassermann et al., 2014). High ...
Entry into anaphase and proteolysis of B-type cyclins depend on a complex containing the tetratricopeptide repeat proteins Cdc16p, Cdc23p, and Cdc27p. This particle, called the anaphase-promoting complex (APC) or cyclosome, functions as a cell cycle-regulated ubiquitin-protein ligase. Two additional subunits of the budding yeast APC were identified: The largest subunit, encoded by the APC1 gene, is conserved between fungi and vertebrates and shows similarity to BIMEp from Aspergillus nidulans. A small heat-inducible subunit is encoded by the CDC26 gene. The yeast APC is a 36S particle that contains at least seven different proteins. ...
The anaphase‐promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that, together with either one of its regulatory co‐activators, Cdc20 or Cdh1, targets multiple mitotic regulators for proteasomal degradation. These include cyclin B1, securin and geminin, making APC/CCdc20 a major factor in directing cell division, sister chromatid separation and DNA replication licensing (Clijsters et al., 2013; Peters, 2006; Pines, 2011). Several questions remain about how the activity of APC/CCdc20 is controlled in mitosis. Phosphorylation of the APC/C by mitotic kinases at the end of prophase leads to an increased affinity for Cdc20 (Kramer et al., 2000; Yudkovsky et al., 2000). The formation of the complex between the APC/C and co‐activator probably induces a conformational change that activates the APC/C (Dube et al., 2005; Kimata et al., 2008), perhaps by facilitating the recruitment of the E2 enzyme UbcH10 (Chang et al., 2014; Van Voorhis and Morgan, 2014). Cdc20 also acts as an APC/C ...
The anaphase promoting complex is a highly conserved E3 ligase complex that mediates the destruction of key regulatory proteins during both mitotic and meiotic divisions. In order to maintain ploidy, this destruction must occur after the regulatory proteins have executed their function. Thus, the regulation of APC/C activity itself is critical for maintaining ploidy during all types of cell divisions. During mitotic cell division, two conserved activator proteins called Cdc20 and Cdh1 are required for both APC/C activation and substrate selection. However, significantly less is known about how these proteins regulate APC/C activity during the specialized meiotic nuclear divisions. In addition, both budding yeast and flies utilize a third meiosis-specific activator. In Saccharomyces cerevisiae, this meiosis-specific activator is called Ama1. This review summarizes our knowledge of how Cdc20 and Ama1 coordinate APC/C activity to regulate the meiotic nuclear divisions in yeast.
The anaphase promoting complex is a highly conserved E3 ligase complex that mediates the destruction of key regulatory proteins during both mitotic and meiotic divisions. In order to maintain ploidy, this destruction must occur after the regulatory proteins have executed their function. Thus, the regulation of APC/C activity itself is critical for maintaining ploidy during all types of cell divisions. During mitotic cell division, two conserved activator proteins called Cdc20 and Cdh1 are required for both APC/C activation and substrate selection. However, significantly less is known about how these proteins regulate APC/C activity during the specialized meiotic nuclear divisions. In addition, both budding yeast and flies utilize a third meiosis-specific activator. In Saccharomyces cerevisiae, this meiosis-specific activator is called Ama1. This review summarizes our knowledge of how Cdc20 and Ama1 coordinate APC/C activity to regulate the meiotic nuclear divisions in yeast.
To determine whether Trim39 could inhibit the APC/C, we added either maltose-binding protein (MBP) or MBP-Trim39 protein to lysates prepared from HeLa cells that had been synchronized in nocodazole and then released (by washout of the nocodazole). As shown in Fig. 1 C, cyclin B1 was quickly degraded in the presence of recombinant MBP protein as these lysates exited from the mitotic arrest, whereas degradation of endogenous cyclin B1 was nearly abolished by addition of recombinant MBP-Trim39. This inhibition was not observed using the C44A mutant, suggesting that E3 ubiquitin ligase activity is required for APC/C inhibition (Fig. 1 C). Indeed, cyclin B1 was more rapidly degraded in the presence of the catalytically inactive Trim39 mutant, suggesting that this protein might interfere with the functioning of the endogenous protein. To confirm a direct role for Trim39 in APC/C inhibition, we incubated APC/C immunoprecipitated from HeLa cells with MBP or MBP-Trim39, E1, E2, ubiquitin, and ...
We reasoned that if Nt-Ac were part of N-terminal degradation signals (Nt-Ac-degrons), it ought to be a determinant of interactions with specialized receptors on Ub ligases or associated proteins. With the possible exception of MARCH6/TEB4 (the Doa10 ortholog), whether such receptors for Nt-Ac-degrons exist in humans is unclear. CDC20 is a well-established cell cycle regulator whose N terminus emerged from our analysis as being thoroughly N terminally acetylated (Fig. 1C). CDC20 is a coactivator of the anaphase-promoting complex/cyclosome (APC/C), an E3 Ub ligase required for the metaphase-anaphase transition (19). CDC20 presents the APC/C with two crucial targets, cyclin B and securin, whose degradation is required for eliciting this fundamental cell cycle transition. CDC20 stability is controlled at multiple levels during cell cycle progression (19), identifying this protein as a promising entry point in the study of the effects of Nt-Ac.. Because Nt-Ac has been previously shown to contribute ...
Chromosomal instability has long been recognized as a hallmark of cancer. Cancer progresses as cells override the intrinsic system of checks and balances that normally prevents them from dividing in the presence of a damaged or aneuploid genome. Chromosomal instability is described as increased chromosome missegregation and often results in aneuploidy or the condition of having too many or too few chromosomes. Under normal physiologic conditions, cell-cycle traverse is carefully controlled by sequential posttranslational modifications, especially E3 ligase-mediated ubiquitination (1, 2). The anaphase-promoting complex/cyclosome (APC/C) is a major E3 ligase complex that promotes the metaphase-to-anaphase transition, and its activation is inhibited until surveillance mechanisms within the cell sense proper metaphase alignment and bipolar spindle attachment of chromosomes (2, 3). Activation of the APC/C occurs via interaction with a cofactor that confers specificity to the complex, either FZR1/CDH1 ...
CDC6 is conserved during evolution and is essential and limiting for the initiation of eukaryotic DNA replication. Human CDC6 activity is regulated by periodic transcription and CDK-regulated subcellular localization. Here, we show that, in addition to being absent from nonproliferating cells, CDC6 is targeted for ubiquitin-mediated proteolysis by the anaphase promoting complex (APC)/cyclosome in G(1). A combination of point mutations in the destruction box and KEN-box motifs in CDC6 stabilizes the protein in G(1) and in quiescent cells. Furthermore, APC, in association with CDH1, ubiquitinates CDC6 in vitro, and both APC and CDH1 are required and limiting for CDC6 proteolysis in vivo. Although a stable mutant of CDC6 is biologically active, overexpression of this mutant or wild-type CDC6 is not sufficient to induce multiple rounds of DNA replication in the same cell cycle. The APC-CDH1-dependent proteolysis of CDC6 in early G(1) and in quiescent cells suggests that this process is part of a ...
The ubiquitin-dependent proteolysis of mitotic cyclin W, which is catalyzed by the anaphase-promoting complex/cyclosome (APC/C) and ubiquitin-conjugating enzyme H10 (UbcH10), begins around the time of the metaphaseCanaphase transition and continues through G1 phase of the next cell cycle. of low-salt buffer, incubated on ice for 20 min, and lysed by douncing using a loose fitting pestle. The lysate was centrifuged at 2000 for 5 min to collect intact nuclei. The cytoplasmic supernatant was obtained by recentrifugation at 14,000 for 20 min. The nuclear pellet was resuspended in 0.5 vol of low-salt buffer and lysed by sonication, and soluble nuclear extracts were obtained by centrifugation of the nuclear lysate at 14,000 for 20 min. All extracts were aliquoted, frozen in liquid nitrogen, and stored at ?80C. Plasmids The following plasmids were used for in vitro transcription and translation: pGEM-human cyclin W (Pines and Hunter, 1989 ), pET5-human cyclin W 1-86, pGEM-human cyclin A (Pines and ...
The eukaryotic cell cycle is driven by a series of complexes comprising cyclins and Cdks. In budding yeast, cell cycle progression is controlled by a single Cdk, Cdc28, whose specificity is dictated by its cyclin regulatory subunit. When Cdk forms complexes with mitotic (M) cyclins (Clb1-4, with Clb2 being the prevalent species), the cells enter mitosis. For cells to exit from mitosis, S phase and M cyclins (collectively called Clbs) must be inactivated (Morgan, 2007). In budding yeast, inactivation of Clb-Cdk is achieved by two redundant mechanisms (Donovan et al., 1994; Schwab et al., 1997; Visintin et al., 1997): (1) accumulation of the Clb-Cdk kinase inhibitor Sic1 (Mendenhall, 1993; Schwob et al., 1994) and (2) degradation of the Clb cyclins by a ubiquitin-dependent proteolysis machinery (Schwab et al., 1997; Visintin et al., 1997; Shirayama et al., 1998). The latter occurs in two steps. At anaphase onset, a specialized ubiquitin ligase known as the anaphase-promoting complex/cyclosome ...
Polo-like kinase 1 (Plk1) plays several roles in mitosis, and it has been suggested to have a role in tumorigenesis. We have previously reported that Plk1 depletion results in cell death in cancer cells, whereas normal cells survive similar depletion. However, Plk1 depletion together with p53 depletion induces cell death in normal cells as well. This communication presents evidence on the sequence of events that leads to cell death in cancer cells. DNA damage is detected at the first S phase following Plk1 depletion and is more severe in Plk1-depleted p53-null cancer cells. As a consequence of Plk1 depletion using lentivirus-based small interfering RNA techniques, prereplicative complex (pre-RC) formation is disrupted at the \(G_1/S\) transition, and DNA synthesis is reduced during S phase of the first cycle after depletion. The levels of geminin, an inhibitor of DNA pre-RC, and Emi1, an inhibitor of anaphase-promoting complex/cyclosome, are elevated in Plk1-depleted cells. The rate of cell ...
The activation of the ubiquitin ligase APC/C requires the phosphorylation of multiple subunits. Because depletion or inactivation of the Xenopus Polo-like kinase 1 (Plx1) in meiotically arrested egg extracts blocks APC/C-dependent degradation of cyclin B ( 5), many investigators have tried to directly link the activities of Plk1 and APC/C. Although Plk1 is able to phosphorylate subunits of the APC/C in vitro, this phosphorylation contributes only marginally to its activation ( 6). In contrast, cyclin B/Cdk1 seems to have a major role in the phosphorylation and activation of the APC/C, thereby triggering its own inactivation at the end of mitosis ( 7).. Although Plk1 can contribute synergistically to the cyclin B/Cdk1-mediated activation of the APC/C ( 6), this observation is not sufficient to explain the crucial role of Plk1/Plx1 in the activation of the APC/C. Intriguing insights have come from studies of the cytostatic factor (CSF) in Xenopus oocytes, where CSF activity prevents parthogenetic ...
Considerable evidence indicates that a polo-like kinase (PLK) plays an important role in cell cycle regulation. PLK is also required for bipolar spindle formation, activation of the anaphase-promoting complex/cyclosome, and cytokinesis. Recent work led to the identification of a PLKK that is thought to be responsible for activation of PLK. Recent work has shown that PLKK is in turn activated by phosphorylation at three sites (Ser482, Ser486 and Ser490). Thus activation of PLK is thought to involve a kinase cascade involving the phosphorylation of Ser482,486,490 in PLKK ...
Claeys, Hannes et al DELLA Signaling Mediates Stress-Induced Cell Differentiation in Arabidopsis Leaves through Modulation of Anaphase-Promoting Complex/Cyclosome Activity. Plant Physiology 159.2 (2012): 739-747. Web. 22 Jan. 2018. ...
The RASSF1A tumor suppressor is one of the most commonly inactivated genes in cancer. To understand why epigenetic silencing of RASSF1A promotes tumorigenesis, I employed a loss of function approach to elucidate the role ...
The anaphase-promoting complex (APC) is a multi-subunit E3 protein ubiquitin ligase that is reponsible for the metaphase to anaphase transition and the exit from mitosis. The subunit APC10 is a one-domain protein homologous to a sequence element, termed the DOC domain, found in several hypothetical proteins that may also mediate ubiquitination reactions, because they contain combinations of either RING finger (see ,PDOC00449,), cullin (see ,PDOC00967,) or HECT (see ,PDOC50237,) domains [1,2,3]. The DOC domain consists of a β-sandwich, in which a five-stranded antiparallel β-sheet is packed on top of a three stranded antiparallel β-sheet, exhibiting a jellyroll fold (see ,PDB:1JHJ; A,) [2,3]. Some proteins known to contain a DOC domain are listed below: ...
The Anaphase promoting complex/ cyclosome (APC/C) is a 1.2 MDa multi-subunit E3 ubiquitin ligase that encodes broad substrate-specificity via its two co-activators Cdc20 and Cdh1 and three principal degrons: the D-box, KEN box and ABBA motif. The regulation of mitotic exit is tightly controlled by the expression and degradation of these two co-activators through stages of the cell cycle. The upregulation of Cdc20 is associated with many cancers including pancreatic, breast and cervical cancers and hepatocellular carcinomas. However, to date, no specific inhibitors of the APC/CCdc20 exist in the clinic. Only two APC/C specific compounds have been discovered: TAME/pro-TAME, which disrupts the C-terminal IR tail of Cdc20 binding to APC3, and Apcin, which disrupts substrate D-box degron binding to Cdc20. Recent studies have highlighted the need for a combination strategy to achieve full inhibition of the APC/CCdc20. We propose a new approach involving the design of constrained peptides to inhibit ...
UbcH3 plays an essential role in the progression of cells from the G1 to S phase of the cell division cycle. One pathway (requiring Cdc34) initiates DNA replication by degrading a CDK (cyclin-dependent kinase) inhibitor. The second pathway, involves the anaphase-promoting complex (APC) which initiates chromosome egregation and exit from mitosis by degrading anaphase inhibitors and mitotic cyclins ...
1GQP: Implications for the Ubiquitination Reaction of the Anaphase-Promoting Complex from the Crystal Structure of the Doc1/Apc10 Subunit.
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Molecular mechanism of sodium acetate tolerance caused by the Thr255Ala mutation in the yeast ubiquitin ligase Rsp5pMolecular mechanism of sodium acetate tolerance caused by the Thr255Ala mutation in the yeast ubiquitin ligase Rsp5p ...
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The anaphase promoting complex (APC/C) is a multi-component ubiquitin ligase complex responsible for targeting cell cycle proteins for degradation. APC/C consists of at least 12 subunits with additional cofactors. Poxvirus anaphase-promoting complex regulator (PACR) is a RING-H2 protein expressed by orf virus (ORFV), the prototype of the Parapoxvirus genus. PACR shares homology with APC/C subunit APC11, but lacks APC11s ubiquitin ligase activity. Inclusion of PACR in APC/C, in place of APC11 has been shown to impair APC/C function causing mitotic arrest, which potentially leads to apoptosis. This investigation was the first step in attempting to make use of PACRs unique ability to promote cell cycle arrest, by cloning PACR into an inducible expression system, Tet-One. Use of an inducible system would minimise PACRs known toxicity to cells and allow PACR to be used as a potential therapeutic to cause cell death of murine melanoma, B16-F10 cells. PACR with a Flag tag was successfully cloned ...
The in vivo and in vitro observations reported here provide a biochemical clue as to how MAD2 executes the mitotic checkpoint. The in vivo association data suggests that a complex including MAD2 and the cyclosome is formed during mitotic checkpoint activation and dissociates once the checkpoint is satisfied. In vitro, the consequence of forcing this interaction by the addition of exogenous MAD2 was to inhibit the cyclin B ubiquitination by the cyclosome and is likely to affect the ubiquitination and degradation of other noncyclin substrates involved in the metaphase-anaphase transition (31-33). Interestingly, it has been shown recently in the fission yeast Schizosaccharomyces pombe that MAD2 behaves genetically as a negative regulator of the cyclosome and that overexpression leads to mitotic arrest (36) in support of the model being proposed here.. The biochemical mechanism that promotes the interaction of MAD2 with the cyclosome during checkpoint activation is unknown, but may rely on the ...
The ubiquitin ligase (E3) Rsp5p is the only member of the Nedd (neural-precursor-cell-expressed, developmentally down-regulated) 4 family of E3s present in yeast. Rsp5p has several proteasome-independent functions in membrane protein trafficking, including a role in the ubiquitination of most plasma membrane proteins, leading to their endocytosis. Rsp5p is also required for the ubiquitination of endosomal proteins, leading to their sorting to the internal vesicles of MVBs (multivesicular bodies). Rsp5p catalyses the attachment of non-conventional ubiquitin chains, linked through ubiquitin Lys-63, to some endocytic and MVB cargoes. This modification appears to be required for efficient sorting, possibly because these chains have a greater affinity for the ubiquitin-binding domains present within endocytic or MVB sorting complexes. The mechanisms involved in the recognition of plasma membrane and MVB substrates by Rsp5p remain unclear. A subset of Rsp5/Nedd4 substrates have a PY motif and are ...
TY - JOUR. T1 - Ubiquitin ligases. T2 - Cell-cycle control and cancer. AU - Nakayama, Keiichi I.. AU - Nakayama, Keiko. PY - 2006/5/1. Y1 - 2006/5/1. N2 - A driving force of the cell cycle is the activation of cyclin-dependent kinases (CDKs), the activities of which are controlled by the ubiquitin-mediated proteolysis of key regulators such as cyclins and CDK inhibitors. Two ubiquitin ligases, the SKP1-CUL1-F-box-protein (SCF) complex and the anaphase-promoting complex/cyclosome (APC/C), are responsible for the specific ubiquitylation of many of these regulators. Deregulation of the proteolytic system might result in uncontrolled proliferation, genomic instability and cancer. Cumulative clinical evidence shows alterations in the ubiquitylation of cell-cycle regulators in the aetiology of many human malignancies. A better understanding of the ubiquitylation machinery will provide new insights into the regulatory biology of cell-cycle transitions and the development of anti-cancer drugs.. AB - A ...
Essential component of the mitotic checkpoint. Required for normal mitosis progression. The mitotic checkpoint delays anaphase until all chromosomes are properly attached to the mitotic spindle. One of its checkpoint functions is to inhibit the activity of the anaphase-promoting complex/cyclosome (APC/C) by blocking the binding of CDC20 to APC/C, independently of its kinase activity. The other is to monitor kinetochore activities that depend on the kinetochore motor CENPE. Required for kinetochore localization of CENPE. Negatively regulates PLK1 activity in interphase cells and suppresses centrosome amplification. Also implicated in triggering apoptosis in polyploid cells that exit aberrantly from mitotic arrest. May play a role for tumor suppression ...
Drawing on their earlier research, the authors found that curcumin specifically binds to and crosslinks to a protein that is involved in cell-cycle regulation. It is known as a checkpoint protein, she said, because it blocks the onset of anaphase until all chromosomes make proper attachments to the spindle. The mitotic checkpoint, or spindle assembly checkpoint (SAC), is the major cell-cycle control mechanism that delays the onset of anaphase during mitosis. One of the primary regulators of the SAC is the anaphase-promoting complex/cyclosome (APC/C ...
Anaphase-promoting complex subunit 7 antibody to detect human Anaphase-promoting complex subunit 7. Validated for western blotting. Try a trial size today.
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FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] A large protein complex, termed the anaphase-promoting complex (APC), or the cyclosome, promotes metaphase-anaphase transition by ubiquitinating its specific substrates such as mitotic cyclins and anaphase inhibitor, which are subsequently degraded by the 26S proteasome. Biochemical studies have shown that the vertebrate APC contains eight subunits. The composition of the APC is highly conserved in organisms from yeast to humans. The exact function of this gene product is not known. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013 ...
A given protein generally has only one native tertiary fold, which is the conformation with the lowest Gibbs free energy. Mad2, a protein involved in the spindle checkpoint, however, has two natively folded states with similar Gibbs free energies. Through binding to its target Cdc20, Mad2 inhibits the multisubunit ubiquitin ligase, the anaphase-promoting complex or cyclosome (APC/C), and delays the onset of anaphase until all sister chromatids achieve bipolar attachment to the mitotic spindle. Without ligand binding or covalent modifications, Mad2 adopts two topologically and functionally distinct native folds in equilibrium under physiological conditions. The transition between the two Mad2 states is regulated by multiple mechanisms and is central to the activation and inactivation of the spindle checkpoint. This review summarizes recent structural and biochemical studies on the two-state behavior of Mad2 and discusses the generality and implications of structural malleability of proteins ...
Protein target information for Chain A, E3 ubiquitin-protein ligase UBR2 (human). Find diseases associated with this biological target and compounds tested against it in bioassay experiments.
Organ morphogenesis in multicellular organisms relies on the coordinated progression of cell proliferation and cell growth. Compared with animals, plants often undergo far more extensive post‐mitotic cell growth, sometimes up to 1000‐fold of original size, and an increase in cell size generally contributes to a larger extent to organ growth. It is also known that some cell types, such as neurons and various hair cells in insects, animals and plants, undergo massive cell growth during differentiation and this is vital for their specialised physiology and function (Sugimoto‐Shirasu and Roberts, 2003). Since the final size of cells is often fairly constant under given conditions, the duration of post‐mitotic cell growth is likely to be developmentally programmed. We still know surprisingly little about how cell size is determined and how developmental signals link to this control. Most of loss‐of‐function mutants with developmental defects display reduced cell‐size phenotypes, ...
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a subunit of the anaphase-promoting complex. This complex is an E3 ubiquitin ligase that regulates progression through the metaphase to anaphase portion of the cell cycle by ubiquitinating proteins which targets them for degradation. [provided by RefSeq, Dec 2011 ...
The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase ...
Core component of multiple cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of…
Core component of multiple cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of…
Opens the Highlight Feature Bar and highlights feature annotations from the FEATURES table of the record. The Highlight Feature Bar can be used to navigate to and highlight other features and provides links to display the highlighted region separately. Links in the FEATURES table will also highlight the corresponding region of the sequence. More... ...
MGWKPSEARGQSQSFQASGLQPRSLKAARRATGRPDRSRAARPTMDPSAHRSRAAPPNMDPDPQAGVQVG 1 - 70 MRVVRGVDWKWGQQDGGEGGVGTVVELGRHGSPSTPDRTVVVQWDQGTRTNYRAGYQGAHDLLLYDNAQI 71 - 140 GVRHPNIICDCCKKHGLRGMRWKCRVCLDYDLCTQCYMHNKHELAHAFDRYETAHSRPVTLSPRQGLPRI 141 - 210 PLRGIFQGAKVVRGPDWEWGSQDGGEGKPGRVVDIRGWDVETGRSVASVTWADGTTNVYRVGHKGKVDLK 211 - 280 CVGEAAGGFYYKDHLPRLGKPAELQRRVSADSQPFQHGDKVKCLLDTDVLREMQEGHGGWNPRMAEFIGQ 281 - 350 TGTVHRITDRGDVRVQFNHETRWTFHPGALTKHHSFWVGDVVRVIGDLDTVKRLQAGHGEWTDDMAPALG 351 - 420 RVGKVVKVFGDGNLRVAVAGQRWTFSPSCLVAYRPEEDANLDVAERARENKSSLSVALDKLRAQKSDPEH 421 - 490 PGRLVVEVALGNAARALDLLRRRPEQVDTKNQGRTALQVAAYLGQVELIRLLLQARAGVDLPDDEGNTAL 491 - 560 HYAALGNQPEATRVLLSAGCRADAINSTQSTALHVAVQRGFLEVVRALCERGCDVNLPDAHSDTPLHSAI 561 - 630 SAGTGASGIVEVLTEVPNIDVTATNSQGFTLLHHASLKGHALAVRKILARARQLVDAKKEDGFTALHLAA 631 - 700 LNNHREVAQILIREGRCDVNVRNRKLQSPLHLAVQQAHVGLVPLLVDAGCSVNAEDEEGDTALHVALQRH 701 - 770 QLLPLVADGAGGDPGPLQLLSRLQASGLPGSAELTVGAAVACFLALEGADVSYTNHRGRSPLDLAAEGRV 771 - 840 ...
MOTIVATION: KEN-box-mediated target selection is one of the mechanisms used in the proteasomal destruction of mitotic cell cycle proteins via the APC/C
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Johnny Rotten once sang; blind acceptance is a sign, of stupid fools who stand in line like EMI. Yeah. He also sang And you thought that we were faking, ...
This complex further complexes with the ubiquitin ligase protein CUL4A and with PARP1. This larger complex rapidly associates ... In NHEJ, DNA Ligase IV, a specialized DNA ligase that forms a complex with the cofactor XRCC4, directly joins the two ends. To ... "Dynamic in vivo interaction of DDB2 E3 ubiquitin ligase with UV-damaged DNA is independent of damage-recognition protein XPC". ... more complex organisms with more complex genomes have correspondingly more complex repair mechanisms. The ability of a large ...
"Identification of a ubiquitin-protein ligase subunit within the CCR4-NOT transcription repressor complex". The EMBO Journal. ... The complex has multiple enzymatic activities as both a poly(A) 3′-5′ exonuclease and a ubiquitin ligase. The complex is ... The human CCR4-Not complex is composed of structural (non-catalytic) subunits and those that have exonuclease and E3 ligase ... Carbon Catabolite Repression-Negative On TATA-less, or CCR4-Not, is a multiprotein complex that functions in gene expression. ...
"Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex". Molecular and Cellular ... Kelch-like ECH-associated protein 1 is a protein that in humans is encoded by the Keap1 gene. Keap1 has four discrete protein ... Abed DA, Goldstein M, Albanyan H, Jin H, Hu L (July 2015). "Discovery of direct inhibitors of Keap1-Nrf2 protein-protein ... "BTB protein Keap1 targets antioxidant transcription factor Nrf2 for ubiquitination by the Cullin 3-Roc1 ligase". Molecular and ...
Cullin-7 acts as scaffold protein in the E3 ubiquitin ligase complex. The role of this complex is to tag damaged and excess ... the CUL7 gene blocks the ability of the cullin-7 protein to bring together the components of this E3 ubiquitin ligase complex. ... This ubiquitin-proteasome system acts as the cell's quality control system by breaking down unwanted proteins. Additionally, ... Once attached to the protein, ubiquitin serves as a signaling molecule to the proteasomes, which then bind to the ubiquinated ...
This is an essential component of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex, which mediates the ... 2001). "Ligand-dependent degradation of Smad3 by a ubiquitin ligase complex of ROC1 and associated proteins". Mol. Biol. Cell. ... This protein is a part of a SCF complex consisting of CUL1, RBX1, SKP1 and SKP2. It also interacts with RNF7. Part of a complex ... Marti A, Wirbelauer C, Scheffner M, Krek W (1999). "Interaction between ubiquitin-protein ligase SCFSKP2 and E2F-1 underlies ...
"The HIV1 Protein Vpr Acts to Promote G2Cell Cycle Arrest by Engaging a DDB1 and Cullin4A-containing Ubiquitin Ligase Complex ... DDB2 is a DCAF protein and is both a ubiquitination substrate of the CRL4 complex and also serves as an E3 ligase protein for ... CUL4A belongs to the cullin family of ubiquitin ligase proteins and is highly homologous to the CUL4B protein. CUL4A regulates ... RBX1 is a core component of Cullin-RING ubiquitin ligase (CRL) complexes and functions to recruit E2 ubiquitin conjugating ...
April 2020). "Structural basis of ER-associated protein degradation mediated by the Hrd1 ubiquitin ligase complex". Science. ... the retrotranslocated misfolded proteins interacts with HRDI E3 ubiquitin ligase. This ligase ubiquitinates the misfolded ... December 2005). "The ubiquitin-domain protein HERP forms a complex with components of the endoplasmic reticulum associated ... As a part of an ER membrane protein complex (that includes VIMP, SEL1, HRD1, and HERP) derlin-1 detects misfolded proteins in ...
"ASB proteins interact with Cullin5 and Rbx2 to form E3 ubiquitin ligase complexes". FEBS Lett. 579 (30): 6796-802. doi:10.1016/ ... Ankyrin repeat and SOCS box protein 13 is a protein that in humans is encoded by the ASB13 gene. The protein encoded by this ... 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957-68. doi: ... 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. doi:10.1038 ...
"ASB proteins interact with Cullin5 and Rbx2 to form E3 ubiquitin ligase complexes". FEBS Lett. 579 (30): 6796-802. doi:10.1016/ ... is an Elongin BC-interacting protein that can assemble with Cullin 5 and Rbx1 to reconstitute an E3 ubiquitin ligase complex". ... Ankyrin repeat and SOCS box protein 2 is a protein that in humans is encoded by the ASB2 gene. The protein encoded by this gene ... 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. doi:10.1038 ...
"Ligand-dependent degradation of Smad3 by a ubiquitin ligase complex of ROC1 and associated proteins". Molecular Biology of the ... "Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex". Nature. 416 (6882): 703-9. doi:10.1038/416703a. PMID ... "Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex". Nature. 416 (6882): 703-9. doi:10.1038/416703a. PMID ... a component of the VHL tumor suppressor complex and SCF ubiquitin ligase". Science. 284 (5414): 657-61. doi:10.1126/science. ...
"The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53". Cell. 75 (3): 495-505. ... the HPV protein E6 binds to a cellular protein called the E6-associated protein (E6-AP, also known as UBE3A), forming a complex ... DNA oncoviruses typically impair two families of tumor suppressor proteins: tumor proteins p53 and the retinoblastoma proteins ... p53 regulates the p21 gene, which produces a protein which binds to the Cyclin D-Cdk4/6 complex. This prevents Rb ...
... is a mammalian gene encoding the protein CBL which is an E3 ubiquitin-protein ligase involved in cell signalling and protein ... Zheng N, Wang P, Jeffrey PD, Pavletich NP (August 2000). "Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin ... Fang N, Fang D, Wang HY, Altman A, Liu YC (2002). "Regulation of immune responses by E3 ubiquitin-protein ligases". Curr. Dir. ... Cbl functions as an E3 ligase, and therefore is able to catalyse the formation of a covalent bond between ubiquitin and Cbl's ...
"Identification of a ubiquitin-protein ligase subunit within the CCR4-NOT transcription repressor complex". The EMBO Journal. 21 ... "An altered-specificity ubiquitin-conjugating enzyme/ubiquitin-protein ligase pair". Journal of Molecular Biology. 337 (1): 157- ... The encoded protein interacts with CNOT1 and has ubiquitin ligase activity. Several transcript variants encoding different ... CCR4-NOT transcription complex, subunit 4 is a protein that in humans is encoded by the CNOT4 gene. The protein encoded by this ...
... structural resemblance of the pVHL/elongin BC/hCUL-2 complex with the ubiquitin ligase complex SKP1/cullin/F-box protein". Proc ... "Identification of the von Hippel-lindau tumor-suppressor protein as part of an active E3 ubiquitin ligase complex". Proc. Natl ... "Association of SAP130/SF3b-3 with Cullin-RING ubiquitin ligase complexes and its regulation by the COP9 signalosome". BMC ... "Drosophila von Hippel-Lindau tumor suppressor complex possesses E3 ubiquitin ligase activity". Biochem. Biophys. Res. Commun. ...
... structural resemblance of the pVHL/elongin BC/hCUL-2 complex with the ubiquitin ligase complex SKP1/cullin/F-box protein". Proc ... "Identification of the von Hippel-lindau tumor-suppressor protein as part of an active E3 ubiquitin ligase complex". Proc. Natl ... "Association of SAP130/SF3b-3 with Cullin-RING ubiquitin ligase complexes and its regulation by the COP9 signalosome". BMC ... subunit mMED8 is an Elongin BC-interacting protein that can assemble with Cul2 and Rbx1 to reconstitute a ubiquitin ligase". ...
... structural resemblance of the pVHL/elongin BC/hCUL-2 complex with the ubiquitin ligase complex SKP1/cullin/F-box protein". Proc ... "Identification of the von Hippel-lindau tumor-suppressor protein as part of an active E3 ubiquitin ligase complex". Proc. Natl ... "Drosophila von Hippel-Lindau tumor suppressor complex possesses E3 ubiquitin ligase activity". Biochem. Biophys. Res. Commun. ... Elongin BC-interacting leucine-rich repeat protein that can assemble with Cul5 and Rbx1 to reconstitute a ubiquitin ligase". J ...
These two proteins are part of the ubiquitin E3 ligase complex involved in the ubiquitin-mediated degradation of WNK1 and WNK4 ... Serine/threonine protein kinase WNK4 also known as WNK lysine deficient protein kinase 4 or WNK4, is an enzyme that in humans ... The mutations in these proteins impair the degradation of WNK1/4. This in turn increases the protein abundance of WNK1/4 and ... WNK4 protein is highly expressed in the distal convoluted tubule (DCT) and the cortical collecting duct (CDD) of the kidney. ...
... damaged DNA binding protein 1 ubiquitin ligase complex. Mutations in this gene are associated with Woodhouse-Sakati syndrome. ... Lee J, Zhou P (2007). "DCAFs, the missing link of the CUL4-DDB1 ubiquitin ligase". Mol. Cell. 26 (6): 775-80. doi:10.1016/j. ... DDB1 and CUL4 associated factor 17 is a protein that in humans is encoded buy the DCAF17 gene. DCAF17 is a nuclear ... 2006). "A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the ...
"APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex". Mol ... "APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex". Mol ... 2004). "TPR subunits of the anaphase-promoting complex mediate binding to the activator protein CDH1". Curr. Biol. 13 (17): ... represents a family of cullin partners with an associated ubiquitin ligase activity". Mol. Cell. UNITED STATES. 3 (4): 535-41. ...
NIPA is a skp1 cullin F-box (SCF)-type ubiquitin E3 ligase (SCFNIPA) complex protein involved in regulating entry into mitosis ... It is a human F-box protein that defines an SCF-type ubiquitin E3 ligase, the formation of which is regulated by cell-cycle- ... Nuclear-interacting partner of ALK (NIPA), also known as zinc finger C3HC-type protein 1 (ZC3HC1), is a protein that in humans ... NIPA is a 60-kDa E3 ligase that contains one C3HC-type zinc finger and one F-box-like region. Moreover, a 50-residue region ( ...
... ubiquitin-conjugating enzymes (E2s) and ubiquitin-protein ligases (E3s). E2s play a key role in the whole ubiquitin (Ub) ... Zheng N, Wang P, Jeffrey PD, Pavletich NP (August 2000). "Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin ... "Human ubiquitin-protein ligase Nedd4: expression, subcellular localization and selective interaction with ubiquitin-conjugating ... Zhang Y, Gao J, Chung KK, Huang H, Dawson VL, Dawson TM (2000). "Parkin functions as an E2-dependent ubiquitin- protein ligase ...
... forms an E3 ubiquitin ligase complex with damaged DNA binding protein 1 (DDB1), Cullin-4A (CUL4A), and regulator of ... The net result is that this ubiquitin ligase complex is important for limb outgrowth in embryos. In the absence of cereblon, ... Cereblon is a protein that in humans is encoded by the CRBN gene. The gene that encodes the cereblon protein is found on the ... DDB1 forms a complex with DDB2 that functions as a DNA damage-binding protein. Furthermore, cereblon and DDB2 bind to DDB1 in a ...
The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), ... and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this ... F-box/LRR-repeat protein 7 is a protein that in humans is encoded by the FBXL7 gene. This gene encodes a member of the F-box ... The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, ...
The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), ... and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this ... F-box/LRR-repeat protein 5 is a protein that in humans is encoded by the FBXL5 gene. This gene encodes a member of the F-box ... 2001). "Toward a Catalog of Human Genes and Proteins: Sequencing and Analysis of 500 Novel Complete Protein Coding Human cDNAs ...
The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), ... and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this ... F-box/WD repeat-containing protein 5 is a protein that in humans is encoded by the FBXW5 gene. This gene encodes a member of ... "WD40 protein FBW5 promotes ubiquitination of tumor suppressor TSC2 by DDB1-CUL4-ROC1 ligase". Genes & Development. 22 (7): 866- ...
The protein complex SCFβ-TrCP1/2 is an E3 ubiquitin ligase that functions in Wee1A ubiquitination. The M-phase kinases Polo- ... Wee1-like protein kinase Cell cycle β-transducin repeat-containing protein 1/2 (β-TrCP1/2) F-box protein-containing SKP1/Cul1/F ... The corresponding proteins are Wee1-like protein kinase and Wee1-like protein kinase 2 which act on the human Cdk1 homologue ... by Clb2-Cdc28 and Cdc5 which may be a signal for ubiquitination and degradation by SCF E3 ubiquitin ligase complex as in higher ...
The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box ... and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this ... F-box only protein 32, also known as "MAFbx", for "Muscle Atrophy F-box gene", and "Atrogin-1," is a protein that in humans is ... de Palma L, Marinelli M, Pavan M, Orazi A (2008). "Ubiquitin ligases MuRF1 and MAFbx in human skeletal muscle atrophy". Joint ...
The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box ... Moreover, Emi1 also assembles a CRL1 complex that targets RAD51 for ubiquitin-mediated degradation. Gene and protein expression ... F-box only protein 5 is a protein that in humans is encoded by the FBXO5 gene. This gene encodes a member of the F-box protein ... ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase". Developmental Cell. 4 (6 ...
Parkin is a protein that functions in complex with CHIP as a ubiquitin ligase and overcomes the accumulation and aggregation of ... more specifically ubiquitin protein ligases called E3, bind to the misfolded protein. Next they align the protein and E2, thus ... Most evidence suggest that the Hrd1 E3 ubiquitin-protein ligase can function as a retrotranslocon or dislocon to transport ... What is the channel for the retrotranslocation of luminal ER proteins?. *Which E3 ligase finally tags the proteins for the ...
KEAP1, an adaptor protein for the cullin 3-dependent E3 ubiquitin ligase complex, mediates the degradation of NRF2; oxidative ... regulating protein-protein interactions, altering protein structure or enzyme activity, changing protein subcellular ... MYPT1 is another protein phosphatase subunit that forms complexes with OGT and is itself O-GlcNAcylated. MYPT1 appears to have ... Protein phosphatase 1 subunits PP1β and PP1γ have been shown to form functional complexes with OGT. A synthetic phosphopeptide ...
"Parkin functions as an E2-dependent ubiquitin- protein ligase and promotes the degradation of the synaptic vesicle-associated ... and structures of the mammalian brain sec6/8 complex and septin filaments". Neuron. 20 (6): 1111-22. PMID 9655500. doi:10.1016/ ... Caltagarone J، Rhodes J، Honer WG، Bowser R (August 1998). "Localization of a novel septin protein, hCDCrel-1, in neurons of ... Hsu SC، Hazuka CD، Roth R، Foletti DL، Heuser J، Scheller RH (June 1998). "Subunit composition, protein interactions, ...
Wnt-protein binding. • protein binding. • protein kinase binding. • ubiquitin protein ligase binding. • transmembrane signaling ... gene family encode 7-transmembrane domain proteins that are receptors for Wnt signaling proteins. The FZD5 protein is believed ... G-protein coupled receptor activity. Cellular component. • clathrin-coated endocytic vesicle membrane. • Golgi apparatus. • ... Frizzled-5 is a protein that in humans is encoded by the FZD5 gene.[5][6][7] ...
PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex. „Genes Dev.". 22 (18 ... Towards a proteome-scale map of the human protein-protein interaction network. „Nature". 437 (7062), s. 1173-8, 2005. DOI: ... a b Ono T, Kitaura H, Ugai H, Murata T, Yokoyama KK, Iguchi-Ariga SM, Ariga H. TOK-1, a novel p21Cip1-binding protein that ... Regulation of cyclin A-Cdk2 by SCF component Skp1 and F-box protein Skp2. „Mol. Cell. Biol.". 19 (1), s. 635-45, 1999. PMID: ...
0090302 ubiquitin protein ligase activity. المكونات الخلوية. • HOPS complex. • غشاء خلوي. • غشاء. • FHF complex. • عصارة خلوية ... ubiquitin-like protein transferase activity. • ‏GO:0001948 ربط بروتيني. • ubiquitin protein ligase binding. • ‏GO:1904264، ‏GO: ... protein transport. • positive regulation of protein binding. • positive regulation of protein phosphorylation. • lysosome ... 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957-68. doi: ...
... an E3 ubiquitin ligase.[79] The APC and the Skp1/Cul1/F-box protein complex (SCF complex) are the two key regulators of cyclin ... Once a protein is tagged with a single ubiquitin molecule, this is a signal to other ligases to attach additional ubiquitin ... was the same protein as ubiquitin.[8] The proteolytic activities of this system were isolated as a multi-protein complex ... ubiquitin ligase by the APC/C(Cdh1) ubiquitin ligase". Nature. 428 (6979): 190-3. doi:10.1038/nature02330. PMID 15014502.. ...
Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7). *Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ... Accumulating data suggests that, while this molecule is, in general, part of growth signaling complex, it plays a more profound ... a b Proto-Oncogene+Proteins+c-sis at the US National Library of Medicine Medical Subject Headings (MeSH) ... Hannink M, Donoghue DJ (1989). "Structure and function of platelet-derived growth factor (PDGF) and related proteins". Biochim ...
... inhibiting the activity of the E3 ubiquitin ligase, resulting in accumulation of the ligase substrates and downregulation of ... Thalidomide and its analogs help with the co-stimulation of T-cells through the B7-CD28 complex by phosphorylating tyrosine on ... Cereblon is a 51 kDa protein localized in the cytoplasm, nucleus and peripheral membrane of cells in numerous parts of the body ... It acts as a component of the E3 ubiquitin ligase, regulating various developmental processes, including embryogenesis, ...
Ubiquitin ligase *Cullin. *Von Hippel-Lindau tumor suppressor. *UBE3A. *Mdm2. *Anaphase-promoting complex ... McClain WH (November 1993). "Rules that govern tRNA identity in protein synthesis". Journal of Molecular Biology. 234 (2): 257- ... An aminoacyl-tRNA synthetase (aaRS or ARS), also called tRNA-ligase, is an enzyme that attaches the appropriate amino acid onto ... For instance, one can start with the gene for a protein that binds a certain sequence of DNA, and, by directing an unnatural ...
protein binding. • cyclin-dependent protein serine/threonine kinase inhibitor activity. • ubiquitin protein ligase binding. • ... cyclin-dependent protein kinase holoenzyme complex. • PCNA-p21 complex. • perinuclear region of cytoplasm. • cell nucleus. • ... protein kinase inhibitor activity. • protein kinase binding. • macromolecular complex binding. Cellular component. • cytoplasm ... Specifically, over the G1/S transition it has been demonstrated that the E3 ubiquitin ligase complex SCFSkp2 induces ...
Stage two involves four key Mur ubiquitin ligase enzymes: MurC (EC),[1] MurD (EC),[2] MurE (EC) [3] and MurF (EC).[4] These ... "Protein Sci. 14 (12): 3039-47. doi:10.1110/ps.051604805. PMC 2253247. PMID 16322581.. ... Ubiquitin ligase *Cullin. *Von Hippel-Lindau tumor suppressor. *UBE3A. *Mdm2. *Anaphase-promoting complex ... 6-diaminopimelate ligase (MurE), and UDP-N-acetylmuramoyl-tripeptide-D-alanyl-D-alanine ligase (MurF). This entry also includes ...
... ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E1 ubiquitin- ... 2004). "The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for selective ubiquitin-like protein activation by ... ligase activity. • protein binding. • protein heterodimerization activity. • acid-amino acid ligase activity. • NEDD8 ... 2nvu: Structure of APPBP1-UBA3~NEDD8-NEDD8-MgATP-Ubc12(C111A), a trapped ubiquitin-like protein activation complex ...
ubiquitin protein ligase binding. • protein complex binding. • metal ion binding. Cellular component. • cyclin-dependent ... cyclin-dependent protein serine/threonine kinase inhibitor activity. • protein binding. • cyclin-dependent protein kinase ... PCNA-p21 complex. Biological process. • regulation of cyclin-dependent protein serine/threonine kinase activity. • G1/S ... protein kinase holoenzyme complex. • nucleus. • nucleoplasm. • cytosol. • intracellular membrane-bounded organelle. • ...
Interaction with CHIP (Carboxyl-terminus of Hsp70 Interacting Protein)-an E3 ubiquitin ligase-allows Hsp70 to pass proteins to ... which then recruits Apaf-1 and dATP/ATP into an apoptosome complex. This complex then cleaves procaspase-9, activating caspase- ... Binding immunoglobulin protein (BiP or Grp78) is a protein localized to the endoplasmic reticulum. It is involved in protein ... The 70 kilodalton heat shock proteins (Hsp70s or DnaK) are a family of conserved ubiquitously expressed heat shock proteins. ...
identical protein binding. Cellular component. • cell-cell adherens junction. • apical junction complex. • trans-Golgi network ... protein binding. • ankyrin binding. • gamma-catenin binding. • beta-catenin binding. • GTPase activating protein binding. • ... catenin complex. • actin cytoskeleton. • flotillin complex. • membrane. • extracellular exosome. • integral component of ... "Dynamics of cadherin/catenin complex formation: novel protein interactions and pathways of complex assembly". The Journal of ...
ubiquitin protein ligase activity. • apolipoprotein A-I receptor binding. • GTP-dependent protein binding. • GTPase activity. • ... negative regulation of protein complex assembly. • epithelial-mesenchymal cell signaling. • actin filament branching. • ... protein binding. • thioesterase binding. • protein kinase binding. • nucleotide binding. • GTP binding. • identical protein ... "Protein Data Bank in Europe. EMBL-EBI. Retrieved 2016-04-22.. *^ "CDC42 (cell division cycle 42 (GTP binding protein, 25kDa))" ...
gamma-tubulin ring complex. • BRCA1-A complex. • ubiquitin ligase complex. • plasma membrane. • nucleoplasm. • condensed ... ubiquitin protein ligase binding. • transcription regulatory region DNA binding. • ubiquitin-protein transferase activity. • ... The ring domain is an important element of ubiquitin E3 ligases, which catalyze protein ubiquitination. Ubiquitin is a small ... "Binding and recognition in the assembly of an active BRCA1/BARD1 ubiquitin-ligase complex". Proc. Natl. Acad. Sci. U.S.A. 100 ( ...
... is a complex of multiple component proteins, including transporters for G6P, glucose, and phosphate. The ... Palmitoyl protein thioesterase. *Ubiquitin carboxy-terminal hydrolase L1. *4-hydroxybenzoyl-CoA thioesterase ... Glucose is then exported from the cell via glucose transporter membrane proteins.[1] This catalysis completes the final step in ... The transfer of the glucose 6-phosphate is carried out by a transporter protein (T1) and the endoplasmic reticulum (ER) ...
ubiquitin ligase complex. • nucleoplasm. • protein complex. • extracellular exosome. Biological process. • ubiquitin-dependent ... ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin- ... ubiquitin-protein transferase activity. • protein binding. • ATP binding. • ubiquitin conjugating enzyme activity. ... "An altered-specificity ubiquitin-conjugating enzyme/ubiquitin-protein ligase pair". Journal of Molecular Biology. 337 (1): 157- ...
Phosphorylation of NRI is catalyzed by NRII, a protein kinase. If NRII is complexed with PIIA then it will function as a ... Ubiquitin ligase *Cullin. *Von Hippel-Lindau tumor suppressor. *UBE3A. *Mdm2. *Anaphase-promoting complex ... RCSB Protein Data Bank. Retrieved 2010-05-08.. *^ a b c d e Krajewski WW, Collins R, Holmberg-Schiavone L, Jones TA, Karlberg T ... The AT:PIID complex will activate GS by deadenylylation.[24] The AT:PIIA and AT:PIID complexes are allosterically regulated in ...
plasma membrane protein complex. • cytoplasm. Biological process. • cellular response to retinoic acid. • ureteric bud ... protein kinase activity. • kinase activity. • protein binding. • protein tyrosine kinase activity. • ATP binding. • Ras guanyl- ... membrane protein proteolysis. • phosphorylation. • transmembrane receptor protein tyrosine kinase signaling pathway. • positive ... Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7). *Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ...
... at least one of two critical proline residues mediates their interaction with the von Hippel Lindau E3 ubiquitin ligase complex ... In protein catabolism, proteins are broken down by proteases into their constituent amino acids. Their carbon skeletons (i.e. ... Several of the enzymes in the cycle may be loosely associated in a multienzyme protein complex within the mitochondrial matrix. ... Evan M.W.Duo Click on genes, proteins and metabolites below to link to respective articles. [§ 1] ...
Ubiquitin ligase *Cullin. *Von Hippel-Lindau tumor suppressor. *UBE3A. *Mdm2. *Anaphase-promoting complex ... The small subunit has a 3-layer beta/beta/alpha structure, and is thought to be mobile in most proteins that carry it. The C- ... DNA sequence and evolution of the CPS domain of the Syrian hamster multifunctional protein CAD". J. Biol. Chem. 265 (18): 10395 ...
ubiquitin protein ligase binding. • peptidase activity. • cysteine-type endopeptidase activity involved in execution phase of ... protein complex binding. • scaffold protein binding. • protein binding. • identical protein binding. • cysteine-type ... protein complex. • mitochondrial outer membrane. • death-inducing signaling complex. • membrane raft. • neuron projection. • ... The N-terminal FADD-like death effector domain of this protein suggests that it may interact with Fas-interacting protein FADD ...
protein binding. • androgen receptor binding. • identical protein binding. • enzyme binding. • ubiquitin protein ligase binding ... SWI/SNF complex. • transcription factor complex. • spindle. • cyclin/CDK positive transcription elongation factor complex. • ... The retinoblastoma protein (protein name abbreviated pRb; gene name abbreviated RB or RB1) is a tumor suppressor protein that ... "MRG15 activates the B-myb promoter through formation of a nuclear complex with the retinoblastoma protein and the novel protein ...
Palmitoyl protein thioesterase. *Ubiquitin carboxy-terminal hydrolase L1. *4-hydroxybenzoyl-CoA thioesterase ... RNA-induced silencing complex. either deoxy- or ribo- *Nuclease S1 *Mung bean nuclease ...
ubiquitin protein ligase binding. • transcription coactivator activity. • RNA polymerase II transcription factor activity, ... transcription factor complex. • nucleoplasm. • myofibril. • nuclear chromatin. • cell nucleus. • cytoplasm. • cytosol. • ... MyoD, also known as myoblast determination protein 1[5], is a protein in animals that plays a major role in regulating muscle ... protein binding. • protein heterodimerization activity. • enzyme binding. • transcription factor activity, RNA polymerase II ...
Ubiquitin ligase *Cullin. *Von Hippel-Lindau tumor suppressor. *UBE3A. *Mdm2. *Anaphase-promoting complex ... proteins. In enzymology, a phosphoribosylformylglycinamidine synthase (EC 6.3.5.3) is an enzyme that catalyzes the chemical ... L-glutamine amido-ligase, (ADP-forming), 2-N-formyl-1-N-(5-phospho-D-ribosyl)glycinamide:L-glutamine, and amido-ligase (ADP- ... This enzyme belongs to the family of ligases, specifically those forming carbon-nitrogen bonds carbon-nitrogen ligases with ...
ubiquitin protein ligase activity. • transcription coactivator activity. • metal ion binding. • ubiquitin-protein transferase ... ubiquitin conjugating enzyme binding. • transferase activity. Cellular component. • cytoplasm. • ubiquitin ligase complex. • ... This protein also interacts with class III ubiquitin-conjugating enzymes (E2s) and may act as a ubiquitin-ligase (E3) in the ... E3 ubiquitin-protein ligase RNF14 is an enzyme that in humans is encoded by the RNF14 gene.[5][6][7] ...
gamma-tubulin ring complex. • BRCA1-A complex. • ubiquitin ligase complex. • membrana plasmática. • cariolinfa. • condensed ... ubiquitin protein ligase binding. • transcription regulatory region DNA binding. • ubiquitin-protein transferase activity. • ... Binding and recognition in the assembly of an active BRCA1/BARD1 ubiquitin-ligase complex». Proc. Natl. Acad. Sci. U.S.A. 100 ( ... Enhancement of BRCA1 E3 ubiquitin ligase activity through direct interaction with the BARD1 protein». J. Biol. Chem. 278 (7): ...
APC2 Cullin Protein and APC11 RING Protein Comprise the Minimal Ubiquitin Ligase Module of the Anaphase-promoting Complex ... Structural resemblance of the pVHL/elongin BC/hCUL-2 complex with the ubiquitin ligase complex SKP1/cullin/F-box protein ... The F-box protein Skp2 is a ubiquitylation target of a Cul1-based core ubiquitin ligase complex: evidence for a role of Cul1 in ... CDC53 and ySKP1, together with the F-box protein GRR1, constitute a putative SCFGRR1 ubiquitin ligase complex that targets G1 ...
F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex.. Skowyra D1, Craig KL ... Skp1, Cdc53, and the F-box protein Cdc4 form a complex, SCFCdc4, which functions as a Sic1 ubiquitin-ligase (E3) in combination ... SCF complexes couple protein kinase signaling pathways to the control of protein abundance. ... Because the constituents of the SCF complex are members of protein families, SCFCdc4 is likely to serve as the prototype for a ...
... Lo ... Keap1 is a BTB-Kelch substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex that functions as a sensor for ... i ,p>When browsing through different UniProt proteins, you can use the basket to save them, so that you can back to find or ... The N terminus of the PGAM5 protein contains a conserved NXESGE motif that binds to the substrate binding pocket in the Kelch ...
Distinct ubiquitin-ligase complexes define convergent pathways for the degradation of ER proteins. Cell. 126:361-373. doi: ... Membrane-anchored ubiquitin ligase complex is required for the turnover of lysosomal membrane proteins. Ming Li, Tatsuhiro ... sterol regulatory element-binding protein. VAcUL-1. vacuole-anchored ubiquitin ligase complex 1. vReD. vacuole membrane ... Membrane-anchored ubiquitin ligase complex is required for the turnover of lysosomal membrane proteins ...
Mediates ubiquitination and subsequent desumoylation/degradation of sumoylated proteins and proteins containing SUMO-like ... E3 ubiquitin-protein ligase complex slx8-rfp subunit rfp1 (EC:2.3.2.27*Search proteins in UniProtKB for this EC number. ... Cited for: FUNCTION IN DEGRADATION OF SUMOYLATED PROTEINS, IDENTIFICATION IN A E3 UBIQUITIN-PROTEIN LIGASE COMPLEX WITH RFP2 ... Cited for: FUNCTION IN DEGRADATION OF SUMOYLATED PROTEINS, IDENTIFICATION IN A E3 UBIQUITIN-PROTEIN LIGASE COMPLEX WITH RFP2 ...
... 0-9. A. B. C. D. E. F. G. H. I. J. K. L. M. N. O ... Inhibition of the anaphase-promoting complex by the Xnf7 ubiquitin ligase.  Casaletto, Jessica B; Nutt, Leta K; Wu, Qiju; ... Tripartite motif 39 (Trim39) is a RING domain-containing E3 ubiquitin ligase able to inhibit the anaphase-promoting complex ( ... Degradation of specific protein substrates by the anaphase-promoting complex/cyclosome (APC) is critical for mitotic exit. We ...
Thus, the Keap1-dependent E3 ubiquitin ligase complex, in contrast to other cullin-dependent E3 ubiquitin ligase complexes ... Keap1 functions as a substrate adaptor protein for a Cul3/Rbx1 E3 ubiquitin ligase complex.Cullin proteins function as ... Keap1 Is a Redox-Regulated Substrate Adaptor Protein for a Cul3-Dependent Ubiquitin Ligase Complex. Donna D. Zhang, Shih-Ching ... is brought into the complex by the substrate adaptor protein, while the Rbx1 protein recruits a ubiquitin-charged E2 protein. ...
... is controlled by an E3 ligase encoded by BOP proteins. ... BLADE-ON-PETIOLE proteins act in an E3 ubiquitin ligase complex ... This shows that BOP proteins act as substrate adaptors in a CUL3BOP1/BOP2 E3 ubiquitin ligase complex, targeting PIF4 proteins ... Here we show that the BOP proteins can act as substrate adaptors in a CUL3BOP1/BOP2 E3 ubiquitin ligase complex that can ... Collectively, our results indicate that the CUL3BOP1/BOP2 E3 ubiquitin ligase complex controls PIF4 protein levels (Figures 3-5 ...
... resulting in inactivation of the RING heterodimer BRCA1/BARD1-mediated E3 ubiquitin ligase function. These findings could ... The binding of the RAPTA compounds to the BRCA1 protein resulted in a release of Zn2+ ions in a dose and time dependent manner ... provide mechanistic insight into the mode of action of RAPTA complexes for on tested BRCA1 model protein. (C) 2017 Elsevier Inc ... In this study, the interaction of some RAPTA compounds with the N-terminal fragment of the BRCA1 RING domain protein was ...
... Matthew F ... How RING E3 ligases mediate E2-to-substrate ubiquitin-like protein (UBL) transfer remains unknown. Here we address how the RING ... E2 and E3 enzymes covalently link ubiquitin-like proteins (UBLs) to their protein targets. The largest family of E3s comprises ... Prototypic CRLs, "SCFs", comprise the scaffold protein CUL1, the RING protein RBX1, the adaptor SKP1, and an F-box protein that ...
UBIQUITIN-CONJUGATING ENZYMES), and ligation of ubiquitin to the substrate protein (UBIQUITIN-PROTEIN LIGASES). ... UBIQUITIN-ACTIVATING ENZYMES), conjugation of ubiquitin to the ligase complex ( ... The complexes play an important role in mediating the selective-degradation of short-lived and abnormal proteins. The complex ... the covalent attachment of UBIQUITIN to other proteins by forming a peptide bond between the C-terminal GLYCINE of UBIQUITIN ...
Quality Control of ER Membrane Proteins by the RNF185/Membralin Ubiquitin Ligase Complex. Journal: Molecular Cell ... Quality Control of ER Membrane Proteins by the RNF185/Membralin Ubiquitin Ligase Complex. ...
Browsing by Subject "Ubiquitin-Protein Ligase Complexes". 0-9. A. B. C. D. E. F. G. H. I. J. K. L. M. N. O. P. Q. R. S. T. U. V ...
Quality Control of ER Membrane Proteins by the RNF185/Membralin Ubiquitin Ligase Complex ... Quality Control of ER Membrane Proteins by the RNF185/Membralin Ubiquitin Ligase Complex ... Quality Control of ER Membrane Proteins by the RNF185/Membralin Ubiquitin Ligase Complex ... New structural insights accelerate drug discovery in the ubiquitin system for cancer therapy ...
Quality Control of ER Membrane Proteins by the RNF185/Membralin Ubiquitin Ligase Complex. ... Quality Control of ER Membrane Proteins by the RNF185/Membralin Ubiquitin Ligase Complex. ...
The ubiquitin conjugating (E2) enzyme encoded by CDC34 (UBC3) in Saccharomyces cerevisiae is required for the G1 to S ... Ubiquitin-Conjugating Enzymes * Ubiquitin-Protein Ligase Complexes * Anaphase-Promoting Complex-Cyclosome * Ubiquitin-Protein ... such as CDC34-specific ubiquitin protein ligases) that govern the substrate selectivity of CDC34. Congruent results ... The ubiquitin conjugating (E2) enzyme encoded by CDC34 (UBC3) in Saccharomyces cerevisiae is required for the G1 to S ...
CF patients harbor mutations in the CFTR gene that lead to misfolding of the resulting CFTR protein, rendering it inactive and ... Proteasome Endopeptidase Complex / physiology* * Ubiquitin-Protein Ligase Complexes / physiology* Substances * CFTR protein, ... The aberrantly folded CFTR protein then undergoes polyubiquitylation, carried out by an E1-E2-E3 ubiquitin ligase system, ... This ubiquitin-dependent loss of misfolded CFTR protein can be inhibited by the application of corrector drugs that aid CFTR ...
We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their ... InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites ... SCF E3 ubiquitin ligase complex F-box protein GRR1. Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Bakers yeast). ... Proteins matched: F-box domain (IPR001810) This domain is found in the following proteins: Showing 121 to 140 of 106596 results ...
Nanobody-targeted E3-ubiquitin ligase complex degrades nuclear proteins.. Shin YJ, Park SK, Jung YJ, Kim YN, Kim KS, Park OK, ... Transfer-RNA-mediated enhancement of ribosomal proteins S6 kinases signaling for cell proliferation. ...
Ubiquitin-protein Ligase Complexes. Complexes of enzymes that catalyze the covalent attachment of UBIQUITIN to other proteins ... UBIQUITIN-CONJUGATING ENZYMES), and ligation of ubiquitin to the substrate protein (UBIQUITIN-PROTEIN LIGASES). ... Photosystem Ii Protein Complex. A large multisubunit protein complex found in the THYLAKOID MEMBRANE. It uses light energy ... Protein Multimerization. The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from ...
Its key role in governing protein homoeostasis has made VCP/p97 an appealing anticancer drug target. Here, we provide evidence ... Together, our data point to an interconnected role of VCP/p97 and GCN2 in maintaining cancer cell metabolic and protein ... VCP/p97 regulates numerous cellular functions by mediating protein degradation through its segregase activity. ... Distinct ubiquitin-ligase complexes define convergent pathways for the degradation of ER proteins. Cell. 2006;126:361-73. ...
... complex detects UV-light-induced pyrimidine dimers throughout the genome; however, it remains unknown how these lesions are ... and identify slide-assisted site exposure as a mechanism by which high-affinity DNA-binding proteins can access otherwise ... In humans, the UV-damaged DNA-binding protein (UV-DDB) ... The ubiquitin ligase activity in the DDB2 and CSA complexes is ... UV-induced ubiquitylation of XPC protein mediated by UV-DDB-ubiquitin ligase complex. Cell 121, 387-400 (2005). ...
Cul4a is the core protein of CRLs E3 ubiquitin ligase complex; while it is known that Cul4a is responsible for various cancers ... It is a scaffold protein of the modular, multisubunit E3 ubiquitin ligase complex, which dynamically combines and degrades ... Cul4a acts as the core of the CRLs E3 ubiquitin ligase, and its complex can bind multiple substrates [9]. Here, we reported ... We identified PARP1 as a novel binding protein of Cul4a ubiquitin ligase in physiological state, and the interaction is ...
Ubiquitin-Protein Ligase Complexes. Polyploidy. Aneuploidy. Cytokinesis. Cyclin B. Chromosomes, Human. RNA Interference. ... Ubiquitin. Proteasome Endopeptidase Complex. Cyclin B1. Tosylarginine Methyl Ester. Ubiquitination. Time-Lapse Imaging. ...
E3 ubiquitin-protein ligase RNF8 in complex with Ubiquitin-conjugating enzyme E2 N and Polyubiquitin-B ... E3 ubiquitin-protein ligase RNF8 in complex with Ubiquitin-conjugating enzyme E2 N and Polyubiquitin-B. Coordinates. PDB Format ... Ubiquitin-conjugating enzyme E2 N: AD. E3 ubiquitin-protein ligase RNF8: BC. Polyubiquitin-B: EF. SMTL:PDB. SMTL Chain Id:. PDB ... Hodge, C.D. et al., RNF8 E3 Ubiquitin Ligase Stimulates Ubc13 E2 Conjugating Activity That Is Essential for DNA Double Strand ...
... have become versatile tools to study dynamics of endogenous proteins in living cells. Additionally, sdAbs conjugated to organic ... have become versatile tools to study dynamics of endogenous proteins in living cells. Additionally, sdAbs conjugated to organic ... Genetically encoded intrabodies fused to fluorescent proteins (chromobodies) ... Genetically encoded intrabodies fused to fluorescent proteins (chromobodies) ...
... is a ubiquitin ligase involved in regulation of the cell cycle through ubiquitination-dependent substrate proteolysis. Many ... viral proteins have been shown to interact with the APC/C, derailing cell cyc ... Ubiquitin-Protein Ligase Complexes / antagonists & inhibitors, metabolism*. Viral Proteins / metabolism. Virus Diseases / drug ... 0/Antineoplastic Agents; 0/Viral Proteins; EC 6.3.2.19/Ubiquitin-Protein Ligase Complexes; EC 6.3.2.19/anaphase-promoting ...
... substrate receptors to direct the degradation of proteins involved in a wide spectrum of cellular functions. Aberrant ... substrate receptors to direct the degradation of proteins involved in a wide spectrum of cellular functions. Aberrant ... The cullin 4-RING ubiquitin ligase (CRL4) family employs multiple DCAF (DDB1-CUL4 associated factors) ... The cullin 4-RING ubiquitin ligase (CRL4) family employs multiple DCAF (DDB1-CUL4 associated factors) ...
E3 ubiquitin ligases can either be single proteins or protein complexes.. Ubiquitin is attached to amino groups of either the N ... in combination with one of many E3 ubiquitin ligases, transfer the ubiquitin monomer to the substrate. The E3 ubiquitin ligase ... Conversely, the levels of the short-lived p53 protein are normally kept low by the mdm-2 ubiquitin ligase that stimulates p53 ... The single E1 ubiquitin-activating enzyme primes ubiquitin monomers, allowing their covalent attachment to substrate proteins. ...
  • As part of an effort to identify components and substrates of a putative human SCF complex, we isolated hSKP1 in a two-hybrid screen with hCUL1, the closest human homologue of CDC53 . (pnas.org)
  • F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex. (nih.gov)
  • Degradation of specific protein substrates by the anaphase-promoting complex/cyclosome (APC) is critical for mitotic exit. (duke.edu)
  • Prototypic CRLs, "SCFs", comprise the scaffold protein CUL1, the RING protein RBX1, the adaptor SKP1, and an F-box protein that both binds SKP1 and recruits substrates for RBX1-mediated ubiquitination 1 , 5 , 6 . (pubmedcentralcanada.ca)
  • We suggest that this region interacts with substrates of CDC34 or with trans-acting factors (such as CDC34-specific ubiquitin protein ligases) that govern the substrate selectivity of CDC34. (nih.gov)
  • The cullin-RING ubiquitin ligases (CRLs) are the largest E3 ligase family in eukaryotes, and ubiquitinate a wide array of substrates involved in cell cycle, signaling, DNA damage response, gene expression, chromatin remodeling, and embryonic development. (frontiersin.org)
  • Within the E2-E3 complex, the RING domain-containing Rbx1/ROC1/Hrt1 or Rbx2/SAG adaptor bridges E2 binding to the cullin carboxyl terminus, which is necessary for transfer of ubiquitin to all cullin substrates. (frontiersin.org)
  • The cullin amino terminus binds cullin-specific adaptors, which in turn recruit distinct classes of substrate receptors that target substrates to the E2-CRL complex for ubiquitination and subsequent degradation by the 26S proteasome. (frontiersin.org)
  • While the pp71-mediated degradation of the retinoblastoma family of proteins requires proteasome function, it occurs without the attachment of ubiquitin to the substrates and in the absence of a functioning ubiquitin-conjugation system. (pnas.org)
  • The cellular machinery that adds ubiquitin to substrates consists of three main enzyme classes. (pnas.org)
  • Projects involve specific structure/function questions regarding BRCA1 and BARD1, developing novel strategies for discovering BRCA1 substrates, and more general mechanistic questions about ubiquitin transfer reactions. (washington.edu)
  • The Cullins assemble a large number of distinct ubiquitin ligases by binding to ROC1, a RING protein, and to several distinct targeting subunits that recruit substrates for ubiquitination ( 28 ). (aacrjournals.org)
  • Creating inhibitors that will block the in vivo activities of specific SCF ubiquitin ligases may provide identification of substrates of these uncharacterized F-box proteins. (asm.org)
  • But ETO also contains a BTB (Broad-complex, Tramtrack, Bic-a-brac) domain that is associated with adaptor proteins that link substrates to ubiquitin ligase complexes that mark proteins for proteasomal degradation. (sciencemag.org)
  • Taken together, our data suggest that the plant CUL4-DDB1A CSAat1A and B complex represents a unique mechanism to promote ubiquitination of substrates in response to DNA damage. (plantcell.org)
  • The C-terminal region of F-Box proteins is also composed of various modular domains that interact with target substrates, often in a phosphorylation-dependent manner. (cellsignal.com)
  • The specificity of SCF CDC4 is thought to be governed by ySKP1 and the F-box-containing subunit CDC4, which together form a substrate receptor that tethers SIC1 to the complex. (pnas.org)
  • Alternative SCF complexes (SCF GRR1 ) assembled with GRR1 instead of CDC4 bind G 1 cyclins but not SIC1, suggesting that there exist multiple SCF complexes in yeast whose substrate specificities are dictated by the identity of the F-box subunit ( 7 ). (pnas.org)
  • This gene encodes a WD repeat protein, which interacts with Cockayne syndrome type B (CSB) protein and with p44 protein, a subunit of the RNA polymerase II transcription factor IIH. (genecards.org)
  • ERCC8 (ERCC Excision Repair 8, CSA Ubiquitin Ligase Complex Subunit) is a Protein Coding gene. (genecards.org)
  • Acts as an adapter for CUL3 to target the serine/threonine-protein phosphatase 2A (PP2A) subunit PPP2R5B for ubiquitination and subsequent proteasomal degradation, thus promoting exchange with other regulatory subunits (PubMed:23135275). (nih.gov)
  • A well-known group of multi-subunit E3 ligases are the Cullin-Ring ubiquitin ligases (CLRs), which are based around a Cullin core. (biologists.org)
  • Pip1p, a new subunit of the SCF-Pop ubiquitin ligase complex in S. pombe. (patentgenius.com)
  • FUNCTION: Catalytic subunit of the probable trimeric SNF1-related CC protein kinase (SnRK) complex, which may play a role in a signal CC transduction cascade regulating gene expression and carbohydrate CC metabolism in higher plants. (univ-lyon1.fr)
  • May be a subunit of a SCF ubiquitin ligase CC complex and thus be involved in proteasomal ubiquitination. (univ-lyon1.fr)
  • SUBUNIT: Subunit of a probable heterotrimeric complex consisting CC of an alpha catalytic (KIN10 or KIN11) subunit, and a beta (KINB) CC and a gamma (KING or SNF4) non-catalytic regulatory subunits. (univ-lyon1.fr)
  • CC Potential subunit of a SCF ubiquitin ligase complex consisting of CC a SNF1-related protein kinase, SKP1 and CUL1. (univ-lyon1.fr)
  • This process is initiated by a ubiquitin-activating enzyme (E1), which activates ubiquitin by adenylation and becomes linked to it via a thiolester bond. (pnas.org)
  • Ubiquitin then is transferred to a ubiquitin-conjugating enzyme, E2. (pnas.org)
  • Skp1, Cdc53, and the F-box protein Cdc4 form a complex, SCFCdc4, which functions as a Sic1 ubiquitin-ligase (E3) in combination with the ubiquitin conjugating enzyme (E2) Cdc34 and E1. (nih.gov)
  • The ubiquitin conjugating (E2) enzyme encoded by CDC34 (UBC3) in Saccharomyces cerevisiae is required for the G1 to S transition of the cell cycle. (nih.gov)
  • We found that a construct encoding a chimeric RAD6-CDC34 ubiquitin conjugating enzyme, in which the 21 residue acidic carboxyl-terminal domain of RAD6 has been replaced with the 125 residue carboxyl-terminal domain of CDC34, performed the essential functions of CDC34 in vivo. (nih.gov)
  • Cullins serve as elongated scaffolds that assemble functional E3 complexes by utilizing distinct adaptors to recruit substrate receptors and the ubiquitin-charged E2 conjugating enzyme (Figure 1 ). (frontiersin.org)
  • RING protein adaptors (R) bind the ubiquitin (Ub)-charged E2 conjugating enzyme at the cullin C-terminus. (frontiersin.org)
  • The single E1 ubiquitin-activating enzyme primes ubiquitin monomers, allowing their covalent attachment to substrate proteins. (pnas.org)
  • Inactivation of the E1 enzyme rapidly depletes the pool of activated ubiquitin, inhibiting the synthesis of polyubiquitin chains and ubiquitin-mediated proteolysis. (pnas.org)
  • The E1 enzyme transfers the activated ubiquitin to one of many E2 carrier enzymes, which, in combination with one of many E3 ubiquitin ligases, transfer the ubiquitin monomer to the substrate. (pnas.org)
  • The E3 ubiquitin ligase binds to both the substrate and the E2 enzyme, assembling them in the correct geometry for ubiquitin transfer. (pnas.org)
  • A ubiquitin-activating enzyme (E1) with ATP as a substrate, catalyzes the formation of a thioester bond between itself and ubiquitin, and it then transfers the activated ubiquitin to a ubiquitin-conjugating enzyme (E2). (aacrjournals.org)
  • The latter provides a docking site for an E2 enzyme, and in yeast, the major E2 associated with SCF complexes is Cdc34p. (asm.org)
  • Proteins and Enzymes: A total of 65 new enzyme classes have been added to the category of Enzymes. (nih.gov)
  • Several new major enzyme categories include: DNA Repair Enzymes, Metalloexopeptidases, Oxidoreductases Acting on CH-CH Group Donors, Proprotein Convertases, and Ubiquitin-Protein Ligase Complexes. (nih.gov)
  • Both are protein motifs that enable the binding of the E2-conjugating enzyme, the protein that provides the ubiquitin molecules. (biologists.org)
  • Our analyses suggest a model where the Bmi-1-Ring1B complex stabilizes the interaction between the E2 enzyme and the nucleosomal substrate to allow efficient ubiquitin transfer. (rcsb.org)
  • Several studies have reported that NSCLC expresses several self-defense genes that are involved in the protection against anticancer drugs, including phase II detoxifying enzyme genes, antioxidant genes, and drug efflux protein genes ( 4 - 7 ). (aacrjournals.org)
  • The F-Box domain mediates interaction with SKP1, which links F-Box proteins to the core ubiquitin-ligase complex that is composed of Rbx1, cdc53/Cul1 and the E2 conjugating enzyme cdc34. (cellsignal.com)
  • ENZYME REGULATION: Inactivated by the begomovirus AL2 protein or CC the curtovirus L2 protein. (univ-lyon1.fr)
  • VCP/p97 regulates numerous cellular functions by mediating protein degradation through its segregase activity. (nature.com)
  • 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)
  • Gunjan A, Verreault A. A Rad53 kinase-dependent surveillance mechanism that regulates histone protein levels in S. cerevisiae. (springer.com)
  • Proteomic Screen for Cellular Targets of the Vaccinia Virus F10 Protein Kinase Reveals that Phosphorylation of mDia Regulates Stress Fiber Formation. (mcw.edu)
  • Chk1 regulates cell cycle progression, in part, by phosphorylating the Cdc25A protein phosphatase ( 1 - 4 ). (aacrjournals.org)
  • The ubiquitin (Ub)-proteasome proteolytic pathway regulates the abundance of polypeptides involved in a variety of processes such as the cell division cycle, immune response, and developmental pathways (for reviews see references 5 , 12 , and 30 ). (asm.org)
  • A vertebrate hemerythrin domain in an E3 ubiquitin ligase complex senses and regulates cellular iron levels. (sciencemag.org)
  • Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization and neurite outgrowth. (abcam.com)
  • Our understanding of how ubiquitin regulates cellular function has greatly expanded recently, spurred by discoveries of protein families involved in ubiquitin conjugation and de-conjugation and of non-proteasomal signaling functions for ubiquitin. (keystonesymposia.org)
  • Ubiquitin regulates an enormous range of cellular processes. (keystonesymposia.org)
  • Hsp90 regulates the folding or degradation of its client proteins by forming multi-component complexes with other chaperones. (mayo.edu)
  • We have reconstituted the ubiquitination pathway for the Cdk inhibitor Sic1 using recombinant proteins. (nih.gov)
  • section describes the metabolic pathway(s) associated with a protein. (uniprot.org)
  • This protein is involved in the pathway protein ubiquitination, which is part of Protein modification. (uniprot.org)
  • View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification . (uniprot.org)
  • Most intracellular protein degradation is handled by the ubiquitin-proteasome pathway ( 3 , 4 ). (pnas.org)
  • Tagging proteins for degradations in the proteasome pathway. (brainscape.com)
  • Which proteins recognise misfolded proteins in aggresome-autophagy pathway? (brainscape.com)
  • How are misfolded proteins in aggresome-autophaphy pathway tagged? (brainscape.com)
  • This study shows that Chk1 abundance is regulated by the Cul4A/DDB1 ubiquitin ligase during an unperturbed cell division cycle, in response to replicative stress and on heat shock protein 90 inhibition, and that deregulation of the Chk1/Cul4A/DDB1 pathway perturbs the ionizing radiation-induced G 2 checkpoint. (aacrjournals.org)
  • c-Cbl and Cbl-b ligases mediate 17-allylaminodemethoxygeldanamycin-induced degradation of autophosphorylated Flt3 kinase with internal tandem duplication through the ubiquitin proteasome pathway. (addgene.org)
  • Ubiquitin ligase trapping identifies an SCF(Saf1) pathway targeting unprocessed vacuolar/lysosomal proteins. (yeastgenome.org)
  • This review discusses our current understanding of the small ubiquitin-like modifier (SUMO) pathway and how it functionally intersects with Ras signaling in cancer. (pubmedcentralcanada.ca)
  • Recent studies have shown that the SUMO pathway can both regulate Ras/MAPK pathway activity directly and support Ras-driven oncogenesis through the regulation of proteins that are not direct Ras effectors. (pubmedcentralcanada.ca)
  • Grr1, an F-box protein involved in Cln destruction, forms complexes with Skp1 and Cdc53 and binds phosphorylated Cln1 and Cln2, but not Sic1. (nih.gov)
  • The NEDD8-modified CUL1 assembles with SKP1-F-box protein-substrate, RBX1 binds a ubiquitin-charged E2 such as UBCH5 or CDC34, and ubiquitin is ligated to a substrate 15 , 16 . (pubmedcentralcanada.ca)
  • The F-box protein is one of the four components of the SCF (SKp1, Cullin, F-box protein) complex, which mediates ubiquitination of proteins targeted for degradation by the proteasome, playing an essential role in many cellular processes. (mdpi.com)
  • Most of the characterized FBPs are components of the SCF (SKp1, Cullin, F-box protein) E3 ubiquitin-ligase complex. (mdpi.com)
  • Substrate-recognition component of the SCF ( SKP1 - CUL1 -F-box protein)-type E3 ubiquitin ligase complex. (rcsb.org)
  • Part of a SCF ( SKP1 -cullin-F-box) protein ligase complex. (rcsb.org)
  • SCF (Skp1-Cul1/Cdc53-F-box) complexes represent a major family of Ub ligases that are evolutionarily conserved, being present in all eukaryotic taxa (for reviews see references 6 , 7 , 19 , and 30 ). (asm.org)
  • The archetypal CLR is the Cullin-1 -based SCF (Skp1, Cullin-1, a Ring protein and an F-box protein) complex. (biologists.org)
  • The N terminus of Cullin-1 binds to a linking protein such as Skp1 and via this to an F-box protein that binds the substrate. (biologists.org)
  • Both complexes contain the COP9 signalosome (CSN), cullin, SKP1, and Roc1 and display ubiquitin ligase activity differentially regulated by CSN, involved in diverse mechanisms of NER in response to UV ( 17 ). (asm.org)
  • In particular, Nup159, a nucleoporin exclusively located on the cytoplasmic side of the NPC, was monoubiquitylated by the Cdc34/SCF (Skp1-Cdc53-F-box E3 ligase) enzymes. (rupress.org)
  • Corrector molecules elevate cellular CFTR protein levels by protecting the protein from degradation and aiding folding, promoting its maturation and localization to the apical plasma membrane. (nih.gov)
  • Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage. (nature.com)
  • The cullin 4-RING ubiquitin ligase (CRL4) family employs multiple DDB1-CUL4 associated factors substrate receptors to direct the degradation of proteins involved in a wide spectrum of cellular functions. (frontiersin.org)
  • However, addition of such large protein tags (~20-25 kDa) to the N- or the C-terminus may affect the expression level, activity, and localization, and for some targets, it was shown that expression of the corresponding fusion protein affects cellular morphology or function ( 6 - 8 ). (frontiersin.org)
  • Protein degradation plays a role in many cellular processes, such as cell cycle regulation, antigen presentation, and the disposal of denatured, unfolded, or oxidized proteins ( 1 - 3 ). (pnas.org)
  • Martinez,IM, Chrispeels,MJ: Genomic analysis of the unfolded protein response in Arabidopsis shows its connection to important cellular processes. (amazonaws.com)
  • αB-Crystallin (αB) and HSP27 belong to the class of small Heat Shock Proteins (sHSPs) whose levels of expression increase under conditions of cellular stress, viz. (washington.edu)
  • sHSPs form an integral part of the cellular chaperone network by maintaining aggregation-prone proteins in a soluble state. (washington.edu)
  • Although a few have been identified to be involved in important biological pathways, such as the cell division cycle and coordinating cellular responses to changes in environmental conditions, the role of the overwhelming majority of F-box proteins is not clear. (asm.org)
  • Cellular iron homeostasis is maintained by the coordinate posttranscriptional regulation of genes responsible for iron uptake, release, use, and storage through the actions of the iron regulatory proteins IRP1 and IRP2. (sciencemag.org)
  • Gene Ontology (GO) terms that describe the function of a complex, the biological process in which it participates, or its cellular location. (yeastgenome.org)
  • A gene on chromosome 14q24.3 that encodes a member of the WD-repeat protein family, which are involved in various cellular processes, including cell cycle progression, signal transduction, apoptosis and gene regulation. (thefreedictionary.com)
  • SAG, a Novel Zinc RING Finger Protein that Protects Cells from Apoptosis Induced by Redox Reagents", Molecular and Cellular Biology 19: 3145-3155 (Apr. (patentgenius.com)
  • SAG, a novel zinc RING finger protein that protects cells from apoptosis induced by redox agents, Molecular and Cellular Biology. (patentgenius.com)
  • The goal of the laboratory is to understand how protein complexes regulate cellular behavior. (icgeb.org)
  • This protein corrupts the cellular checkpoint mechanisms that guard cell division and the transcription, replication and repair of DNA. (bio-medicine.org)
  • These proteins are also some of the most broadly acting cellular oncogenes, and include cyclin E, c-Myc, Notch, and c-Jun," noted Dr. Clurman. (bio-medicine.org)
  • The disease is caused by production of progerin, a mutated version of the nuclear structural protein lamin A, which leads to numerous cellular defects and decreased numbers of mesenchymal stem cells (MSCs) through unknown mechanisms. (cancer.gov)
  • The researchers took wild-type fibroblasts with inducible green fluorescent protein (GFP)-labeled progerin and treated them with several hundred siRNAs to find genes that prevented the formation of multiple cellular HGPS phenotypes, such as increased DNA damage. (cancer.gov)
  • CAND1controls the substrate specificity of several cullin-containing E3 ubiquitin ligase complexes, key components of the cellular protein degradation machinery. (cancer.gov)
  • Our studies show that the cellular E3 ubiquitin ligase MKRN1 is a novel pVII interacting protein in HAdV-5 infected cells. (diva-portal.org)
  • Indeed, ~20% of all ubiquitin-proteasomal degradation is estimated to result from E3 activities of NEDD8-activated CRLs 18 . (pubmedcentralcanada.ca)
  • This type of degradation seems to be much less common than the proteasomal degradation of ubiquitinated proteins ( 20 ). (pnas.org)
  • We found that an E3 ubiquitin ligase complex containing the FBXL5 protein targets IRP2 for proteasomal degradation. (sciencemag.org)
  • Under unstimulated conditions, Nrf2 is retained in the cytoplasm by the anchor protein Kelch-like ECH-associated protein-1 (Keap1) and is maintained at a reduced level by the Keap1-dependent ubiquitination and proteasomal degradation systems ( 9 , 10 ). (aacrjournals.org)
  • Purified pVHL appears to have ubiquitin ligase activity, directing HIF-α toward proteasomal degradation ( 19 ). (aacrjournals.org)
  • Molecular chaperones function to refold misfolded proteins or to target them for proteasomal degradation. (mayo.edu)
  • We report that the propeptide module is the destabilizing element targeting the precursor pVII protein for proteasomal degradation. (diva-portal.org)
  • Surprisingly, the endogenous MKRN1 protein underwent proteasomal degradation during the prolonged HAdV-5 infection. (diva-portal.org)
  • Further application of biochemical assays similar to those described here can now be used to identify regulators/components of hCUL1-based SCF complexes, to determine whether the hCUL2-hCUL5 proteins also are components of ubiquitin ligase complexes in human cells, and to screen for chemical compounds that modulate the activities of the hSKP1 and hCUL1 proteins. (pnas.org)
  • Mutations and deletions in components of ubiquitin ligase complexes that lead to alterations in protein turnover are important mechanisms in driving tumorigenesis. (jci.org)
  • Therefore, we made a model of a CUL1-RBX1-UBC12 complex based on structures of UBC12, cullin-RBX1 complexes, and other E2s bound to other RING domain proteins ( Supplementary Fig. 1 ) 2 - 4 , 7 . (pubmedcentralcanada.ca)
  • In addition, Cul1- and Cul4A-containing E3 ubiquitin ligases have been shown to ubiquitinate Chk1 during periods of prolonged replication stress ( 27 ). (aacrjournals.org)
  • While some intrabodies are based on non-antibody scaffolds like peptides, monobodies, or designed ankyrin repeat proteins ( 9 - 12 ), most intrabodies are derived from immunoglobulins (IgGs) comprising a variable heavy (VH) and variable light domain, artificially linked to form a single-chain variable fragment (scFv) ( 13 - 15 ). (frontiersin.org)
  • The openings to this cavity permit only denatured proteins to enter, where they are processively cleaved to small peptides. (pnas.org)
  • Amino Acids, Peptides and Proteins (D12): 246 new descriptors were added. (nih.gov)
  • This removal is achieved by protein degradation via the 26S proteasome, which can degrade proteins down to peptides. (biologists.org)
  • Check out links to articles that cite our custom service antibodies, peptides, and proteins in major peer-reviewed journals, organized by research category. (abgent.com)
  • Here, we show that hCUL1 associates with hSKP1 in vivo and directly interacts with both hSKP1 and the human F-box protein SKP2 in vitro , forming an SCF-like particle. (pnas.org)
  • Ohta A, Schumacher FR, Mehellou Y, Johnson C, Knebel A, Macartney TJ, Wood NT, Alessi DR, Kurz T. The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction. (medlineplus.gov)
  • E3 (protein ligase complex) - interacts with protein and ubiquitin. (brainscape.com)
  • The coiled-coil motif is involved in homodimerization, the Sec7 domain contains guanine-nucleotide exchange protein activity, and the PH domain interacts with phospholipids and is responsible for association of PSCDs with membranes. (genecards.org)
  • Human Cytomegalovirus UL135 Interacts with Host Adaptor Proteins To Regulate Epidermal Growth Factor Receptor and Reactivation from Latency. (mcw.edu)
  • Skp2 is the F-box protein component of an SCF-type ubiquitin ligase that interacts specifically with p27 Kip1 and thereby promotes its ubiquitylation and degradation. (aacrjournals.org)
  • Interacts with the begomovirus AL2 CC protein and the curtovirus L2 protein. (univ-lyon1.fr)
  • However, very little is known about mechanisms that govern the regulation of its membrane proteins. (rupress.org)
  • The nature of the protein kinase(s) and the ubiquitin E3 ligase(s) involved in the regulation of PIF stability in response to light have just started to be explored. (elifesciences.org)
  • Regulation of neddylation and deneddylation of cullin1 in SCFSkp2 ubiquitin ligase by F-box protein and substrate. (semanticscholar.org)
  • Cullin-RING ubiquitin E3 ligase regulation by the COP9 signalosome. (nature.com)
  • INTRODUCTION: The anaphase promoting complex/cyclosome (APC/C) is a ubiquitin ligase involved in regulation of the cell cycle through ubiquitination-dependent substrate proteolysis. (biomedsearch.com)
  • Members of this family appear to mediate the regulation of protein sorting and membrane trafficking. (genecards.org)
  • Multiple strategies, including down-regulation of major histocompatibility complex (MHC) class I and class II expression ( 2 - 4 ) and persistence, have been developed by the bacteria to evade the immune system. (mcponline.org)
  • Through the regulation of RBBP8/CtIP protein turnover, plays a key role in DNA damage response, favoring DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR) (PubMed:27561354). (nih.gov)
  • Petroski MD and Deshaies RJ (2005) Function and regulation of cullin-RING ubiquitin ligases. (yeastgenome.org)
  • K. L.-C. Wang, H. Yoshida, C. Lurin, J. R. Ecker, Regulation of ethylene gas biosynthesis by the Arabidopsis ETO1 protein. (sciencemag.org)
  • Polycomb group proteins Bmi-1 and Ring1B are core subunits of the PRC1 complex, which plays important roles in the regulation of Hox gene expression, X-chromosome inactivation, tumorigenesis, and stem cell self-renewal. (rcsb.org)
  • Regulation of the human papillomavirus type 18 E6/E6AP ubiquitin ligase complex by the HECT domain-containing protein EDD. (icgeb.org)
  • The SnRK complex may also be involved CC in the regulation of fatty acid synthesis by phosphorylation of CC acetyl-CoA carboxylase and in assimilation of nitrogen by CC phosphorylating nitrate reductase. (univ-lyon1.fr)
  • The SCF ubiquitin ligase complex of budding yeast triggers DNA replication by catalyzing ubiquitination of the S phase cyclin-dependent kinase inhibitor SIC1. (pnas.org)
  • SCF complexes couple protein kinase signaling pathways to the control of protein abundance. (nih.gov)
  • A Conserved Gammaherpesvirus Protein Kinase Targets Histone Deacetylases 1 and 2 To Facilitate Viral Replication in Primary Macrophages. (mcw.edu)
  • The Chk1 protein kinase preserves genome integrity in normal proliferating cells and in cells experiencing replicative and genotoxic stress. (aacrjournals.org)
  • Chk1 is a serine/threonine protein kinase that functions to maintain genome integrity in normal cycling cells and in cells exposed to replicative and genotoxic stress ( 1 , 2 ). (aacrjournals.org)
  • Phosphorylation of Cdc25A by Chk1 targets it for ubiquitin-mediated proteolysis and prevents it from binding to and activating cyclin-dependent kinase 1/cyclin B1 inappropriately during the S and G 2 phases of the cell division cycle ( 1 , 2 , 5 - 7 ). (aacrjournals.org)
  • Drugs that block Chk1 kinase activity or enhance its proteolysis by interfering with binding to heat shock protein 90 (HSP90) are currently being tested as anticancer agents ( 14 - 17 ). (aacrjournals.org)
  • Phosphorylation and polyubiquitination of transforming growth factor beta-activated kinase 1 are necessary for activation of NF-kappaB by the Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor. (addgene.org)
  • Expression of CBLΔexon8 and CBLΔexon8+9 in FLT3-WT-Ba/F3 cells induced growth factor-independent proliferation associated with autophosphorylation of FLT3 and activated the downstream targets signal transducer and activator of transcription 5 (STAT5) and protein kinase B (AKT). (aacrjournals.org)
  • Therefore, it is of particular note that analysis of CBL should be introduced in routine leukemia diagnostics, as patients who harbor CBL mutations might benefit from treatment with FLT3 protein tyrosine kinase inhibitors. (aacrjournals.org)
  • SIMILARITY: Belongs to the protein kinase superfamily. (univ-lyon1.fr)
  • CAMK CC Ser/Thr protein kinase family. (univ-lyon1.fr)
  • SIMILARITY: Contains 1 protein kinase domain. (univ-lyon1.fr)
  • Emi2-mediated inhibition of E2-substrate ubiquitin transfer by the anaphase-promoting complex/cyclosome through a D-box-independent mechanism. (duke.edu)
  • Vertebrate eggs are arrested at Metaphase II by Emi2, the meiotic anaphase-promoting complex/cyclosome (APC/C) inhibitor. (duke.edu)
  • E3s have been implicated in substrate recognition and, in one case, transfer of ubiquitin from E2 to a substrate via an E3-ubiquitin-thiolester intermediate ( 5 ). (pnas.org)
  • Ubiquitin ligases direct the transfer of ubiquitin onto substrate proteins and thus target the substrate for proteasome-dependent degradation. (asm.org)
  • The N terminus of the PGAM5 protein contains a conserved NXESGE motif that binds to the substrate binding pocket in the Kelch domain of Keap1, whereas the C-terminal PGAM domain binds Bcl-X(L). Keap1-dependent ubiquitination of PGAM5 results in proteasome-dependent degradation of PGAM5. (uniprot.org)
  • Nrf2 binds DNA as a heterodimer with one of several small Maf proteins and is a potent activator of ARE-dependent transcription. (asm.org)
  • Finally, RBX1 binds another ubiquitin-charged CDC34, and ubiquitin is transferred to Lys48 on a substrate-linked ubiquitin. (pubmedcentralcanada.ca)
  • Under periods of replicative stress, the ATRIP/ATR module binds to single-stranded DNA and, together with Rad17 and the 9-1-1 complex, activates Chk1 in a Claspin-dependent manner ( 18 - 22 ). (aacrjournals.org)
  • The C terminus of Cullin protein binds to a Ring protein, e.g. (biologists.org)
  • On exposure to oxidative or xenobiotic stress, Keap1-dependent ubiquitin ligase activity is inhibited and Nrf2 can translocate to the nucleus, where it forms a heterodimer with small Maf proteins and binds to a consensus sequence called the antioxidant response element. (aacrjournals.org)
  • In its native form, pVHL typically forms multimeric complex with several other moieties (Elongin B, Elongin C, Cul2, and Rbx1) and binds to hypoxia inducible factor-α (HIF-α) in the setting of hypoxia ( 16-18 ). (aacrjournals.org)
  • Werner helicase interacting protein 1 (WRNIP1) binds polyubiquitin via its zinc finger domain. (icgeb.org)
  • The translation initiation factor eIF-4E binds to a common motif shared by the translation factor eIF-4 gamma and the translational repressors 4E-binding proteins. (google.co.uk)
  • Eukaryote cells are exposed to both intrinsic and extrinsic sources of reactive oxygen species and other chemically reactive molecules that can damage biological macromolecules, including DNA, proteins, and lipids ( 22 ). (asm.org)
  • Additional ubiquitin molecules are added to the lysine 48 residue of the previous ubiquitin in the chain ( 9 ). (pnas.org)
  • E3 ubiquitin ligases function as part of the ubiquitin-proteasome system by tagging damaged and excess proteins with molecules called ubiquitin. (medlineplus.gov)
  • False colored section of mouse colon prior to treatment with Gamitrinibs, a class of small molecules designed by Kang and colleagues (page 454) to selectively target the heat shock protein-90 (Hsp90) network compartmentalized in tumor mitochondria. (jci.org)
  • Interactions with other relevant participants such as small molecules (purple), sub-complexes (yellow), and other subunits (red) are also shown. (yeastgenome.org)
  • This table lists all participants of the complex (proteins, small molecules, nucleic acids, etc.) and their respective stoichiometry. (yeastgenome.org)
  • Many key transcription factors, signaling molecules and structural proteins necessary for myogenesis and muscle growth have been identified. (biomedcentral.com)
  • As not all proteins have to be degraded, an active selection mechanism is in place that marks the degradation targets by adding multiple ubiquitin molecules. (biologists.org)
  • In addition to RTKs, Ras can also be activated by other signaling molecules including G protein-coupled receptors (GPCR), calcium influx and the T-cell receptor (TCR) complex. (pubmedcentralcanada.ca)
  • That heat shock proteins recognize abnormal tau is particularly impressive, but heat shock proteins are also actively involved in antigen presentation through major histocompatibility complex molecules leading to a robust immune response. (mayo.edu)
  • ETO1 interacted with the CUL3A protein, which functions as a scaffold in ubiquitin E3 ligase complexes. (sciencemag.org)
  • Importantly, DNA damage induces the formation of many new protein complexes and Ubiquitin functions as a scaffold, or bridge, to hold these complexes together. (icgeb.org)
  • Keap1 assembles into a functional E3 ubiquitin ligase complex with Cul3 and Rbx1 that targets multiple lysine residues located in the N-terminal Neh2 domain of Nrf2 for ubiquitin conjugation both in vivo and in vitro. (asm.org)
  • Nonetheless, to date none of the 7 RBX1 structures is in a conformation demonstrating any of its UBL ligase functions 7 , 8 , 13 , 19 . (pubmedcentralcanada.ca)
  • Reconstitution of G.sub.1 Cyclin Ubiquitination with Complexes Containing SCF.sup.Grr1 and Rbx1 , Science. (patentgenius.com)
  • Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase. (semanticscholar.org)
  • The formation of γ-H2AX foci is believed to promote effective repair by aiding in the accumulation of checkpoint adaptor proteins and the recruitment of DNA repair machinery such as Brca1 and 53BP1 to damage sites ( 33 , 35 , 54 ). (asm.org)
  • F-Box proteins act as modular E3 ubiquitin ligase adaptor proteins within the SCF complex responsible for phosphorylation-mediated ubiquitination. (cellsignal.com)
  • Whereas genetic analysis has revealed that SIC1 proteolysis requires CDC4, G 1 cyclin proteolysis appears to depend on a distinct F-box-containing protein known as GRR1 ( 8 ). (pnas.org)
  • Chk1 is regulated by reversible phosphorylation and by ubiquitin-mediated proteolysis. (aacrjournals.org)
  • Recently, there have been several reports of proteasome-dependent, ubiquitin-independent degradation of proteins in vivo ( 15 - 19 ). (pnas.org)
  • These modifications are not simply related to proteasome-dependent protein turnover of the NPC but, as exemplified by Nup159 ubiquitylation, participate to the cell cycle progression. (rupress.org)
  • The cullin-RING ubiquitin ligases are multisubunit complexes that ubiquitinate various proteins. (semanticscholar.org)
  • These degron motifs are often small linear amino acid stretches that provide docking sites for the E3 complexes to bind and ubiquitinate the target protein. (mcponline.org)
  • The von Hippel-Lindau tumor-suppressor gene product forms a stable complex with human CUL-2, a member of the Cdc53 family of proteins. (semanticscholar.org)
  • F-box proteins (FBPs) are a large and diverse family of proteins present in all eukaryotes that are characterized by presence of the F-box domain [ 1 ]. (mdpi.com)
  • This gene encodes a member of the kelch-like family of proteins that share a common domain structure consisting of an N-terminal broad-complex, tramtrack, bric-a-brac/poxvirus and zinc finger domain and C-terminal kelch repeat motifs. (nih.gov)
  • Once attached to the protein, ubiquitin serves as a signaling molecule to the proteasomes, which then bind to the ubiquinated proteins and degrades them. (wikipedia.org)
  • Conjugation of complex polyubiquitin chains to WRNIP1. (icgeb.org)
  • Generation of stable cell lines is a widely used technique for continuous recombinant protein production. (bioportfolio.com)
  • Schroder,M, Friedl,P: Overexpression of recombinant human antithrombin III in Chinese hamster ovary cells results in malformation and decreased secretion of recombinant protein. (amazonaws.com)
  • Recombinant protein encompassing a sequence within the center region of human BTBD6. (genetex.com)
  • Abgent has over fifteen years of experience producing recombinant proteins in E. coli and mammalian cells (CHO and HEK293, etc), and we have added a powerful yeast expression platform to our menu of services. (abgent.com)
  • Moreover, systemic delivery of recombinant MG53 protein ameliorates the impact of a range of injury insults on the heart, skeletal muscle, lung, kidney, skin, and brain. (aspetjournals.org)
  • Unexpectedly, we identified a RING domain-containing E3 ligase Tul1 and its interacting proteins in the Dsc complex that are important for the ubiquitination of Cot1 and partial ubiquitination of Zrt3. (rupress.org)
  • Altered protein turnover due to impaired COP1 function led to accumulation and enhanced basal and cytokine-induced activity of STAT3. (jci.org)
  • ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity, Molecular Cell. (patentgenius.com)
  • Much knowledge of RING E3s derives from studies of the modular multiprotein cullin-RING ligases (CRLs) 1 . (pubmedcentralcanada.ca)
  • Our current research focuses on a superfamily of multi-component protein complexes, known as cullin-RING ubiquitin ligases. (washington.edu)
  • In addition to uncovering extended specificities of UBR E3 ligases, we characterized two related Cullin-RING E3 ligase complexes, Cul2-ZYG11B and Cul2-ZER1, that act redundantly to target N-terminal glycine. (mcponline.org)
  • This protein is part of a ubiquitin ligase complex that adds ubiquitin to proteins to mark them for destruction by the cell. (bio-medicine.org)
  • CF patients harbor mutations in the CFTR gene that lead to misfolding of the resulting CFTR protein, rendering it inactive and mislocalized. (nih.gov)
  • Cullin 4a (Cul4a) is a 87 kDa protein with a gene located at 13q34 in the high expression region of the oncogene. (hindawi.com)
  • The retinoblastoma protein (p105), p107, and p130 are each targeted for degradation by the pp71 protein, which is encoded by the UL82 gene of human cytomegalovirus. (pnas.org)
  • The Cullin 7 gene contains instructions for making the protein Cullin-7. (wikipedia.org)
  • The KLHL3 gene provides instructions for making a protein that plays a role in the cell machinery that breaks down (degrades) unwanted proteins, called the ubiquitin-proteasome system. (medlineplus.gov)
  • It is unknown if WNK1 is affected by the abnormal E3 ubiquitin ligase complex or whether WNK1 plays a role in development of PHA2 caused by KLHL3 gene mutations. (medlineplus.gov)
  • The protein encoded by this gene is a member of the PSCD family. (genecards.org)
  • CYTH1 (Cytohesin 1) is a Protein Coding gene. (genecards.org)
  • GO annotations related to this gene include ubiquitin-protein transferase activity and DNA-dependent ATPase activity . (genecards.org)
  • SmgGDS is a transient nucleolar protein that protects cells from nucleolar stress and promotes the cell cycle by regulating DREAM complex gene expression. (mcw.edu)
  • HRD gene-encoded proteins required for Ubc7p-Hmg2p cross-linking. (asm.org)
  • The CUL7 gene provides instructions for making a protein called cullin-7. (medlineplus.gov)
  • The protein produced from the OBSL1 gene is thought to help maintain normal levels of cullin-7. (medlineplus.gov)
  • Mutations in the CUL7 or OBSL1 gene 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)
  • This diagram displays Gene Ontology terms (green) and subunits (blue) that are shared between the given macromolecular complex (black) and other yeast complexes (yellow). (yeastgenome.org)
  • The number of sequences annotated by searching protein and gene ontology databases was 10,465. (biomedcentral.com)
  • The average coverage of the annotated isotigs was x40 containing 5655 unique gene IDs and 785 full-length cDNAs coding for proteins containing 58-1536 amino acids. (biomedcentral.com)
  • The vif gene encodes a small and highly basic protein rich in tryptophans [ 5 , 6 ]. (mdpi.com)
  • UV-DDB is a heterodimer complex consisting of either Cockayne syndrome gene A (CSA, p48) or DDB2 (p48) existing in nearly identical complexes via interaction with DDB1 (p127) ( 17 , 57 ). (asm.org)
  • Protein sequence for the given gene in S288C and other strains, when available. (yeastgenome.org)
  • revealed the novel ALS/FTD-associated gene CCNF, which encodes cyclin F protein, a component of the SCF E3 ubiquitin-ligase complex. (alzforum.org)
  • In addition, we show that inhibition of the Cul3 protein reduces HAdV-5 E1A gene expression. (diva-portal.org)
  • In this study, the interaction of some RAPTA compounds with the N-terminal fragment of the BRCA1 RING domain protein was investigated. (epfl.ch)
  • Dynamic in vivo interaction of DDB2 E3 ubiquitin ligase with UV-damaged DNA is independent of damage-recognition protein XPC. (nature.com)
  • Here, oxidative stress was induced by hydrogen peroxide (H 2 O 2 ), CCK-8 assay and flow cytometry were used to analyze cell viability and apoptosis rate, western blot and immunofluorescence were used to quantitatively analyze the expression of protein, ROS fluorescence kit was used to detect reactive oxygen species (ROS) formation, and coimmunoprecipitation was used to identify protein interaction. (hindawi.com)
  • The F-box domain consists of a conserved sequence of about 50 amino acids implicated in the interaction with core members of the complex [ 1 , 10 , 11 ]. (mdpi.com)
  • Interaction of an intracellular pentraxin with a BTB-Kelch protein is associated with ubiquitylation, aggregation and neuronal apoptosis. (addgene.org)
  • In this paper, we will review the interaction of the lentiviral Vif proteins with the APOBEC3 proteins, with an emphasis on sheep APOBEC3 and maedi-visna virus (MVV) Vif. (mdpi.com)
  • The two regions of interaction have a synergistic effect on the E3 ligase activity. (rcsb.org)
  • The laboratory uses high throughput mass spectrometry to gain insights into the protein interaction networks from a variety of normal and pathological conditions. (icgeb.org)
  • A split-yellow fluorescent protein assay showed that this interaction occurs in the nucleus, consistent with the idea that the CUL4-DDB1A-CSA complex functions as a nuclear E3 ubiquitin ligase. (plantcell.org)
  • The association of CC the SCF complex with the proteasome may be mediated by PAD1 and CC seems to be inhibited by the interaction with PRL1. (univ-lyon1.fr)
  • It is a scaffold protein of the modular, multisubunit E3 ubiquitin ligase complex, which dynamically combines and degrades protein in a periodic manner [ 9 ]. (hindawi.com)
  • The proteasome is a large, multisubunit complex that exists in cells in two main forms, a 20S and 26S species. (pnas.org)
  • Keap1 is a BTB-Kelch substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex that functions as a sensor for thiol-reactive chemopreventive compounds and oxidative stress. (uniprot.org)
  • In this report, we demonstrate that Keap1 functions as a substrate adaptor protein for a Cul3-dependent E3 ubiquitin ligase complex. (asm.org)
  • This shows that BOP proteins act as substrate adaptors in a CUL3 BOP1/BOP2 E3 ubiquitin ligase complex, targeting PIF4 proteins for ubiquitination and subsequent degradation. (elifesciences.org)
  • Substrate-specific adapter for CUL3 E3 ubiquitin-protein ligase complex (PubMed:14528312). (nih.gov)
  • Adapter protein for the CUL3 E3 ubiquitin-protein ligase complex. (genetex.com)
  • We also found that the Cul3-based E3 ubiquitin ligase complex alter the precursor pVII protein stability via binding to the propeptide sequence. (diva-portal.org)
  • E2 and E3 enzymes covalently link ubiquitin-like proteins (UBLs) to their protein targets. (pubmedcentralcanada.ca)
  • Here, we show that damaged DNA-binding protein 1 (DDB1), a triple β propeller adapter protein, targets the Cul4 E3 ubiquitin ligase complex to Chk1. (aacrjournals.org)
  • We found that miR-424 targets the E3 ubiquitin ligase COP1 and identified STAT3 as a key substrate of COP1 in promoting tumorigenic and cancer stem-like properties in prostate epithelial cells. (jci.org)
  • RNF8 E3 Ubiquitin Ligase Stimulates Ubc13 E2 Conjugating Activity That Is Essential for DNA Double Strand Break Signaling and BRCA1 Tumor Suppressor Recruitment. (expasy.org)
  • Here, we describe the degradation of the retinoblastoma family of tumor suppressor proteins by the proteasome in the absence of polyubiquitination. (pnas.org)
  • These two mechanisms differ in their biology and epidemiology: direct tumor viruses must have at least one virus copy in every tumor cell expressing at least one protein or RNA that is causing the cell to become cancerous. (wikipedia.org)
  • We have discovered that the protein FBXO11 is a novel tumor suppressor in B-cells," said senior study author Michele Pagano, MD , the May Ellen and Gerald Jay Ritter Professor of Oncology and Professor of Pathology at NYU Langone Medical Center and a Howard Hughes Medical Institute Investigator. (healthcanal.com)
  • The von Hippel-Lindau tumor suppressor protein. (semanticscholar.org)
  • Identification of the von Hippel-lindau tumor-suppressor protein as part of an active E3 ubiquitin ligase complex. (semanticscholar.org)
  • Several vascular endothelial growth factor receptor-directed therapies classically thought to function as antiangiogenics may also have complex effects upon the tumor microenvironment including the associated immune cell milieu. (aacrjournals.org)
  • VHL encodes a tumor suppressor protein (pVHL) with a molecular weight between 24 and 30 kDa ( 15 ). (aacrjournals.org)
  • New binding target for oncogenic viral protein ( The DNA tumor virus simian virus 40 pro. (bio-medicine.org)
  • The DNA tumor virus simian virus 40 produces the Large T antigen which inactivates two of the cell's most important cancer-preventing proteins, p53 and pRb. (bio-medicine.org)
  • T antigen also inactivates some of the most important proteins that protect cells against malignant transformation, including tumor suppressor proteins p53 and pRb. (bio-medicine.org)
  • These inhibitors are counteracted by the Vif proteins encoded by most lentiviruses. (mdpi.com)
  • Hsp90 inhibitors (HSP90i) convert the Hsp90 complex from a catalyst for protein folding into one that induces protein degradation (Fig. 1). (mayo.edu)
  • Moreover, hCUL1 complements the growth defect of yeast cdc53 ts mutants, associates with ubiquitination-promoting activity in human cell extracts, and can assemble into functional, chimeric ubiquitin ligase complexes with yeast SCF components. (pnas.org)
  • Genetic analysis shows that BOP2 promotes photo-morphogenesis and modulates thermomorphogenesis by suppressing PIF4 activity, through a reduction in PIF4 protein level. (elifesciences.org)
  • The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. (nature.com)
  • CRL activity is regulated by the Nedd8 post-translational modification: the ubiquitin-like Nedd8 protein is conjugated to cullins in a manner highly analogous to ubiquitination. (frontiersin.org)
  • FBPs are structurally and functionally diverse, and their activity is crucial for selecting proteins that will be targeted by the SCF complex. (mdpi.com)
  • Selective protein degradation is an efficient and rapid way of terminating protein activity. (biologists.org)
  • The RING finger protein Ring1B is an E3 ligase that participates in the ubiquitination of lysine 119 of histone H2A, and the binding of Bmi-1 stimulates the E3 ligase activity. (rcsb.org)
  • Ras are membrane proteins and their activity is regulated through a GTP/GDP exchange cycle. (pubmedcentralcanada.ca)
  • Progerin, a mutant form of the protein lamin A, sequesters NRF2 and thereby causes its subnuclear mislocalization, resulting in impaired NRF2 transcriptional activity and increased chronic oxidative stress. (cancer.gov)
  • The analyses revealed that the SLR1 protein can be divided into four parts: a GA signal perception domain located at the N terminus, a regulatory domain for its repression activity, a dimer formation domain essential for signal perception and repression activity, and a repression domain at the C terminus. (plantcell.org)
  • CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. (univ-lyon1.fr)
  • Hence, we propose that the MKRN1 is a novel antiviral protein and that HAdV-5 infection counteracts its antiviral activity. (diva-portal.org)
  • Cullin-7 acts as scaffold protein in the E3 ubiquitin ligase complex. (wikipedia.org)
  • SCF is composed of three proteins-ySKP1, CDC53 (Cullin), and the F-box protein CDC4-that are conserved from yeast to humans. (pnas.org)
  • This manuscript describes the detection of sumoylation and ubiquitination of kinetochore proteins, Ndc10 and Ndc80, in the budding yeast Saccharomyces cerevisiae . (jove.com)
  • Components from yeast and human SCF complexes produced in insect cells have been demonstrated previously to possess Ub ligase activities ( 10 , 16 , 37 , 43 ). (asm.org)
  • Proteasome- and SCF-dependent degradation of yeast adenine deaminase upon transition from proliferation to quiescence requires a new F-box protein named Saf1p. (yeastgenome.org)
  • The association of ETO1 protein with ACS was confirmed by yeast two-hybrid assays, in vitro experiments, and immunoprecipitation from plant cells. (sciencemag.org)
  • In this work, we systematically analyze ubiquitylation of the yeast NPC and find that more than half of NPC proteins are conjugated to ubiquitin. (rupress.org)
  • There are at least seven known Cullin proteins in humans, which can assemble into different CLRs. (biologists.org)
  • Using Saccharomyces cerevisiae as a model system, we demonstrate that overproduction of polypeptides corresponding to the amino terminus of the F-box proteins Cdc4p and Met30p results in specific inhibition of their SCF complexes. (asm.org)
  • HAdV encodes the pVII protein, which is involved in nuclear delivery, protection and expression of viral DNA. (diva-portal.org)
  • It is required for the recruitment of XAB2, HMGN1 and TCEA1/TFIIS to a transcription-coupled repair complex which removes RNA polymerase II-blocking lesions from the transcribed strand of active genes. (genecards.org)
  • 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)
  • This combination of high-throughput sequencing and protein identification technologies allows detection of genes and proteins. (biomedsearch.com)
  • We show that this approach can also be used to highlight genes and proteins undergoing dynamic changes in post-transcriptional protein stability. (biomedsearch.com)
  • includes protein coordinates for the domain, a domain Description, a Source and corresponding accession ID, and the number of S. cerevisiae genes that share the same domain. (yeastgenome.org)
  • They identified seven potential genes, performed validation of the four most prominent, and identified cullin-associated NEDD8-dissociated protein 1 (CAND1) for further investigation. (cancer.gov)
  • A major target of the cullin 3-complex is the transcription factor NRF2, which has been implicated in longevity and stress resistance by regulating genes with antioxidant-response elements (AREs) in their promoters. (cancer.gov)
  • These results suggest a common means to inhibit specific SCF complexes in vivo. (asm.org)
  • In vivo protein transduction: delivery of a biologically active protein into the mouse. (semanticscholar.org)
  • To investigate the mode of action of SLR1, we generated transgenic rice expressing a fusion protein consisting of SLR1 and green fluorescent protein (SLR1-GFP) and analyzed the phenotype of the transformants and the subcellular localization of GFP in vivo. (plantcell.org)
  • This ubiquitin-dependent loss of misfolded CFTR protein can be inhibited by the application of 'corrector' drugs that aid CFTR folding, shielding it from the UPS machinery. (nih.gov)
  • With a wide range of proteins being targeted for degradation by the proteasome, the cell overcomes the problem of specificity through a hierarchical order of Ub-conjugating machinery. (asm.org)
  • The cullin-7 protein plays a role in the cell machinery that breaks down (degrades) unwanted proteins, called the ubiquitin-proteasome system. (medlineplus.gov)
  • Targeting the anaphase promoting complex: common pathways for viral infection and cancer therapy. (biomedsearch.com)
  • Many viral proteins have been shown to interact with the APC/C, derailing cell cycle progression in order to facilitate their own replication. (biomedsearch.com)
  • Some viral proteins cause cytotoxicity specifically in tumour cells, providing evidence that targeting the APC/C could be exploited to selectively eliminate cancer cells. (biomedsearch.com)
  • It functions to direct their degradation in the absence of other viral proteins. (pnas.org)
  • A sophisticated, protein receptor-based sensor system has evolved to recognize viral nucleic acids and to trigger a variety of antiviral defense mechanisms. (jci.org)
  • Ubiquitin-regulated nuclear-cytoplasmic trafficking of the Nipah virus matrix protein is important for viral budding. (addgene.org)
  • Dysregulation of these complexes has been associated with multiple human disorders including cancer, neurological disease, and viral infection. (washington.edu)
  • Performed PhD studies with Ken Powell on Herpes Simplex Virus proteins and viral replication. (icgeb.org)
  • Interestingly, the E3L protein rescued the translational defect but did not stimulate viral capsid mRNA accumulation observed with VA RNA. (diva-portal.org)
  • How RING E3 ligases mediate E2-to-substrate ubiquitin-like protein (UBL) transfer remains unknown. (pubmedcentralcanada.ca)
  • It is noteworthy that chronic upregulation of MG53 induces insulin resistance and metabolic diseases, such as type 2 diabetes and its cardiovascular complications, by acting as an E3 ligase to mediate the degradation of insulin receptor and insulin receptor substrate-1. (aspetjournals.org)
  • Intracellular and extracellular signals within the cell highly regulate when and which proteins are tagged with ubiquitin. (wikipedia.org)
  • Thus, expression and intracellular processing of chlamydial proteins into human cells allowed us to identify two bacterial HLA-B27 ligands, including the first endogenous T-cell epitope from C. trachomatis involved in spondyloarthropathy. (mcponline.org)
  • Whereas E2s can attach ubiquitin directly to lysine residues in a substrate, most physiological ubiquitination reactions probably require a ubiquitin ligase, or E3 ( 4 ). (pnas.org)
  • Fbw7 recognizes a destruction signal on certain proteins that need to be degraded and brings them in close proximity to the enzymes that attach ubiquitin. (bio-medicine.org)
  • Human homologues of yCDC34 and ySKP1 have been reported ( 9 , 10 ), and F-box-containing proteins like CDC4 and GRR1 have been identified in many eukaryotes ( 11 ). (pnas.org)
  • DNA is, however, supercoiled and wound around "packaging" proteins called histones (in eukaryotes), and both superstructures are vulnerable to the effects of DNA damage. (wikipedia.org)
  • SCF complexes contain a common set of components, namely, Cdc53p (or cullin in higher eukaryotes), Skp1p, and Hrt1p (alternatively named Rbx1p or Roc1p). (asm.org)
  • Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed. (uniprot.org)
  • Electrophoretic mobility shift assays indicated the presence in nuclear extracts of proteins that bind to this sequence. (aacrjournals.org)
  • Vif does not have a sequence resemblance to known proteins, and sequence similarity between the Vif proteins of lentiviruses is rather limited. (mdpi.com)
  • Protein abundance data, domains, shared domains with other proteins, protein sequence retrieval for various strains, sequence-based physico-chemical properties, protein modification sites, and external identifiers for the protein. (yeastgenome.org)
  • More detailed evidence for these modification sites is presented in the Post-translational Modifications table, located just below the protein sequence. (yeastgenome.org)
  • Tripartite motif 39 (Trim39) is a RING domain-containing E3 ubiquitin ligase able to inhibit the anaphase-promoting complex (APC/C) directly. (duke.edu)
  • p>When browsing through different UniProt proteins, you can use the 'basket' to save them, so that you can back to find or analyse them later. (uniprot.org)
  • Moreover, we found that BOP proteins physically interact with both PIF4 and CULLIN3A and that a CULLIN3-BOP2 complex ubiquitinates PIF4 in vitro. (elifesciences.org)
  • Functional analysis of the spindle-checkpoint proteins using an in vitro ubiquitination assay. (semanticscholar.org)
  • Cancer cells have a heightened dependency on the mechanisms of protein degradation to maintain protein homoeostasis (proteostasis) [ 1 ]. (nature.com)
  • Oncoviruses have been important not only in epidemiology, but also in investigations of cell cycle control mechanisms such as the Retinoblastoma protein. (wikipedia.org)
  • The largest family of E3s comprises the RING cohort, which bind both a UBL-loaded E2 and a protein substrate targeted for UBL transfer 1 . (pubmedcentralcanada.ca)
  • Ubiquitin serves as a signal to specialized cell structures known as proteasomes, which attach (bind) to the tagged proteins and degrade them. (medlineplus.gov)
  • The E3 ligases, which bind to a substrate and attach the ubiquitin molecule, are believed to provide substrate specificity. (biologists.org)
  • Our study demonstrated that the Dsc complex can function at the vacuole to regulate the composition and lifetime of vacuolar membrane proteins. (rupress.org)
  • Quality Control of ER Membrane Proteins by the RNF185/Membralin Ubiquitin Ligase Complex. (natureindex.com)
  • The SCF E3 ubiquitin-ligase complex participates in the recognition and recruitment of target proteins for ubiquitination and degradation by the ubiquitin 26S proteasome system (UPS). (mdpi.com)
  • Our results suggest that the ability of Keap1 to assemble into a functional E3 ubiquitin ligase complex is the critical determinant that controls steady-state levels of Nrf2 in response to cancer-preventive compounds and oxidative stress. (asm.org)
  • Specifically, cullin-7 helps assemble a complex called an E3 ubiquitin ligase, which tags the unneeded proteins for degradation. (medlineplus.gov)
  • May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex. (abcam.com)
  • DCAF4 is thought to act as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex. (thefreedictionary.com)