Anaphase: The phase of cell nucleus division following METAPHASE, in which the CHROMATIDS separate and migrate to opposite poles of the spindle.Anaphase-Promoting Complex-Cyclosome: 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.Ubiquitin-Protein Ligase Complexes: 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).Cdc20 Proteins: Highly conserved proteins that specifically bind to and activate the anaphase-promoting complex-cyclosome, promoting ubiquitination and proteolysis of cell-cycle-regulatory proteins. Cdc20 is essential for anaphase-promoting complex activity, initiation of anaphase, and cyclin proteolysis during mitosis.Cdh1 Proteins: Cdh1 is an activator of the anaphase-promoting complex-cyclosome, and is involved in substrate recognition. It associates with the complex in late MITOSIS from anaphase through G1 to regulate activity of CYCLIN-DEPENDENT KINASES and to prevent premature DNA replication.Mitosis: A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome: A highly evolutionarily conserved subunit of the anaphase-promoting complex (APC-C) containing multiple 34-amino-acid tetratricopeptide repeats. These domains, also found in Apc subunits 6, 7, and 8, have been shown to mediate protein-protein interactions, suggesting that Apc3 may assist in coordinating the juxtaposition of the catalytic and substrate recognition module subunits relative to co-activators and APC-C inhibitors.Cell Cycle Proteins: 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.Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome: The largest subunit of the anaphase-promoting complex. It acts primarily as a scaffold for the proper organization and arrangement of subunits. The C-terminal region of Apc1 contains a series of tandem amino acid repeats that are also seen in the 26S proteasome regulatory particle, and may assist with forming and stabilizing protein-protein interactions.Spindle Apparatus: A microtubule structure that forms during CELL DIVISION. It consists of two SPINDLE POLES, and sets of MICROTUBULES that may include the astral microtubules, the polar microtubules, and the kinetochore microtubules.Securin: Securin is involved in the control of the metaphase-anaphase transition during MITOSIS. It promotes the onset of anaphase by blocking SEPARASE function and preventing proteolysis of cohesin and separation of sister CHROMATIDS. Overexpression of securin is associated with NEOPLASTIC CELL TRANSFORMATION and tumor formation.Cyclin B: A cyclin subtype that is transported into the CELL NUCLEUS at the end of the G2 PHASE. It stimulates the G2/M phase transition by activating CDC2 PROTEIN KINASE.F-Box Proteins: 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.Genes, APC: Tumor suppressor genes located in the 5q21 region on the long arm of human chromosome 5. The mutation of these genes is associated with familial adenomatous polyposis (ADENOMATOUS POLYPOSIS COLI) and GARDNER SYNDROME, as well as some sporadic colorectal cancers.Metaphase: The phase of cell nucleus division following PROMETAPHASE, in which the CHROMOSOMES line up across the equatorial plane of the SPINDLE APPARATUS prior to separation.Ligases: 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.M Phase Cell Cycle Checkpoints: The cellular signaling system that halts the progression of cells through MITOSIS or MEIOSIS if a defect that will affect CHROMOSOME SEGREGATION is detected.Cyclin A2: A widely-expressed cyclin A subtype that functions during the G1/S and G2/M transitions of the CELL CYCLE.Apc5 Subunit, Anaphase-Promoting Complex-Cyclosome: A subunit of the anaphase-promoting complex whose primary function is to provide structural support for the catalytic and substrate-recognition modules of the complex. Apc5, along with Apc4, tethers the tetratricopeptide-coactivator binding subcomplex to the main structural subunit, Apc1.Mad2 Proteins: Mad2 is a component of the spindle-assembly checkpoint apparatus. It binds to and inhibits the Cdc20 activator subunit of the anaphase-promoting complex, preventing the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. Mad2 is required for proper microtubule capture at KINETOCHORES.Cyclin B1: A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.Chromosome Segregation: The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS.Ubiquitin-Protein Ligases: 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.Cell Cycle: 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.Prometaphase: The phase of cell nucleus division following PROPHASE, when the breakdown of the NUCLEAR ENVELOPE occurs and the MITOTIC SPINDLE APPARATUS enters the nuclear region and attaches to the KINETOCHORES.CDC2 Protein Kinase: Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.HeLa Cells: 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.Meiosis: A type of CELL NUCLEUS division, occurring during maturation of the GERM CELLS. Two successive cell nucleus divisions following a single chromosome duplication (S PHASE) result in daughter cells with half the number of CHROMOSOMES as the parent cells.Ubiquitination: 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.Geminin: Geminin inhibits DNA replication by preventing the incorporation of MCM complex into pre-replication complex. It is absent during G1 phase of the CELL CYCLE and accumulates through S, G2,and M phases. It is degraded at the metaphase-anaphase transition by the ANAPHASE-PROMOTING COMPLEX-CYCLOSOME.Schizosaccharomyces pombe Proteins: Proteins obtained from the species Schizosaccharomyces pombe. 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.Apc2 Subunit, Anaphase-Promoting Complex-Cyclosome: Together with the Apc11 subunit, forms the catalytic core of the E3 ubiquitin ligase anaphase-promoting complex (APC-C). Its N-terminus has cullin domains which associate with the RING FINGER DOMAINS of Apc11. Apc2 also interacts with the E2 ubiquitin ligases involved in APC-C ubiquitination reactions.Cyclin A: A cyclin subtype that has specificity for CDC2 PROTEIN KINASE and CYCLIN-DEPENDENT KINASE 2. It plays a role in progression of the CELL CYCLE through G1/S and G2/M phase transitions.Saccharomyces cerevisiae Proteins: 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.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Molecular Sequence Data: 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.Schizosaccharomyces: A genus of ascomycetous fungi of the family Schizosaccharomycetaceae, order Schizosaccharomycetales.Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome: A highly conserved subunit of the anaphase-promoting complex (APC-C) containing multiple 34-amino-acid tetratricopeptide repeats. These domains, also found in Apc3, Apc6, and Apc7, have been shown to mediate protein-protein interactions, suggesting that Apc8 may assist in coordinating the juxtaposition of the catalytic and substrate recognition module subunits relative to coactivators and APC-C inhibitors.Separase: Separase is a caspase-like cysteine protease, which plays a central role in triggering ANAPHASE by cleaving the SCC1/RAD21 subunit of the cohesin complex. Cohesin holds the sister CHROMATIDS together during METAPHASE and its cleavage results in chromosome segregation.Amino Acid Sequence: 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.Fungal Proteins: Proteins found in any species of fungus.Nocodazole: Nocodazole is an antineoplastic agent which exerts its effect by depolymerizing microtubules.Mutation: 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.Nuclear Proteins: 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.Telophase: The final phase of cell nucleus division following ANAPHASE, in which two daughter nuclei are formed, the CYTOPLASM completes division, and the CHROMOSOMES lose their distinctness and are transformed into CHROMATIN threads.Aurora Kinases: A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.Chromatids: Either of the two longitudinally adjacent threads formed when a eukaryotic chromosome replicates prior to mitosis. The chromatids are held together at the centromere. Sister chromatids are derived from the same chromosome. (Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes (GENES, MOS). They function in the cell cycle to maintain MATURATION PROMOTING FACTOR in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time.Xenopus Proteins: Proteins obtained from various species of Xenopus. Included here are proteins from the African clawed frog (XENOPUS LAEVIS). Many of these proteins have been the subject of scientific investigations in the area of MORPHOGENESIS and development.G1 Phase: The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors.Genes, cdc: Genes that code for proteins that regulate the CELL DIVISION CYCLE. These genes form a regulatory network that culminates in the onset of MITOSIS by activating the p34cdc2 protein (PROTEIN P34CDC2).Protein Binding: 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.Oocytes: Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).Protein Subunits: 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.Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS.Ubiquitin: 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.Ubiquitin-Conjugating Enzymes: 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.Xenopus: An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome: A highly conserved subunit of the anaphase-promoting complex (APC-C) containing multiple 34 amino acid tetratricopeptide repeats. These domains, also found in Apc3, Apc7, and Apc8, have been shown to mediate protein-protein interactions, suggesting that Apc6 may assist in coordinating the juxtaposition of the catalytic and substrate recognition module subunits relative to coactivators and APC-C inhibitors.SKP Cullin F-Box Protein Ligases: 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.Saccharomyces cerevisiae: 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.Ubiquitins: 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.Kinetochores: Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle.Proteasome Endopeptidase Complex: 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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.RNA Interference: 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.Chromosomes: In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Recombinant Fusion Proteins: 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.S Phase: Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.Amino Acid Motifs: 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.Cytokinesis: The process by which the CYTOPLASM of a cell is divided.Calcium-Binding Proteins: Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.Drosophila Proteins: 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.Models, Biological: 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.G2 Phase: The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Centromere: The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division.Apc11 Subunit, Anaphase-Promoting Complex-Cyclosome: Together with the Apc2 subunit, forms the catalytic core of the E3 ubiquitin ligase, anaphase-promoting complex-cyclosome. It has a RING H2 domain which interacts with the cullin domain of Apc2. Apc11 also interacts with the E2 ubiquitin ligases involved in APC-C ubiquitination reactions.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Repressor Proteins: 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.Adenomatous Polyposis Coli Protein: A negative regulator of beta-catenin signaling which is mutant in ADENOMATOUS POLYPOSIS COLI and GARDNER SYNDROME.Cadherins: Calcium-dependent cell adhesion proteins. They are important in the formation of ADHERENS JUNCTIONS between cells. Cadherins are classified by their distinct immunological and tissue specificities, either by letters (E- for epithelial, N- for neural, and P- for placental cadherins) or by numbers (cadherin-12 or N-cadherin 2 for brain-cadherin). Cadherins promote cell adhesion via a homophilic mechanism as in the construction of tissues and of the whole animal body.Protein Processing, Post-Translational: 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.Cyclins: A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.Drosophila: A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.RNA, Small Interfering: 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.Protein Stability: The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Chromosomal Proteins, Non-Histone: Nucleoproteins, which in contrast to HISTONES, are acid insoluble. They are involved in chromosomal functions; e.g. they bind selectively to DNA, stimulate transcription resulting in tissue-specific RNA synthesis and undergo specific changes in response to various hormones or phytomitogens.Macromolecular Substances: Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.Apc7 Subunit, Anaphase-Promoting Complex-Cyclosome: A highly conserved subunit of the anaphase-promoting complex (APC-C) containing multiple 34 amino acid tetratricopeptide repeats. These domains, also found in Apc3, Apc6, and Apc8, have been shown to mediate protein-protein interactions, suggesting that Apc7 may assist in coordinating the juxtaposition of the catalytic and substrate recognition module subunits relative to coactivators and APC-C inhibitors.Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Microtubule-Associated Proteins: High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Kinesin: A microtubule-associated mechanical adenosine triphosphatase, that uses the energy of ATP hydrolysis to move organelles along microtubules toward the plus end of the microtubule. The protein is found in squid axoplasm, optic lobes, and in bovine brain. Bovine kinesin is a heterotetramer composed of two heavy (120 kDa) and two light (62 kDa) chains. EC 3.6.1.-.Prophase: The first phase of cell nucleus division, in which the CHROMOSOMES become visible, the CELL NUCLEUS starts to lose its identity, the SPINDLE APPARATUS appears, and the CENTRIOLES migrate toward opposite poles.Bivalvia: A class in the phylum MOLLUSCA comprised of mussels; clams; OYSTERS; COCKLES; and SCALLOPS. They are characterized by a bilaterally symmetrical hinged shell and a muscular foot used for burrowing and anchoring.Endoreduplication: A type of nuclear polyploidization in which multiple cycles of DNA REPLICATION occur in the absence of CELL DIVISION and result in a POLYPLOID CELL.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from SPERM FLAGELLUM; CILIA; and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to COLCHICINE; VINCRISTINE; and VINBLASTINE.Interphase: The interval between two successive CELL DIVISIONS during which the CHROMOSOMES are not individually distinguishable. It is composed of the G phases (G1 PHASE; G0 PHASE; G2 PHASE) and S PHASE (when DNA replication occurs).Aurora Kinase B: An aurora kinase that is a component of the chromosomal passenger protein complex and is involved in the regulation of MITOSIS. It mediates proper CHROMOSOME SEGREGATION and contractile ring function during CYTOKINESIS.Protein Structure, Tertiary: 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.Spermatocytes: Male germ cells derived from SPERMATOGONIA. The euploid primary spermatocytes undergo MEIOSIS and give rise to the haploid secondary spermatocytes which in turn give rise to SPERMATIDS.Cell Nucleus: 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)Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Apc10 Subunit, Anaphase-Promoting Complex-Cyclosome: Apc10 is necessary for coactivator-dependent substrate recognition by the anaphase-promoting complex-cyclosome. It binds the Apc2 subunit, which is a part of the catalytic core, and interacts with coactivators Cdh1 or Cdc20 to recruit substrates to the complex.Centrosome: The cell center, consisting of a pair of CENTRIOLES surrounded by a cloud of amorphous material called the pericentriolar region. During interphase, the centrosome nucleates microtubule outgrowth. The centrosome duplicates and, during mitosis, separates to form the two poles of the mitotic spindle (MITOTIC SPINDLE APPARATUS).Sequence Alignment: 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.Cell Line, Tumor: A cell line derived from cultured tumor cells.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Adenomatous Polyposis Coli: A polyposis syndrome due to an autosomal dominant mutation of the APC genes (GENES, APC) on CHROMOSOME 5. The syndrome is characterized by the development of hundreds of ADENOMATOUS POLYPS in the COLON and RECTUM of affected individuals by early adulthood.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Embryo, Nonmammalian: The developmental entity of a fertilized egg (ZYGOTE) in animal species other than MAMMALS. For chickens, use CHICK EMBRYO.Saccharomycetales: An order of fungi in the phylum Ascomycota that multiply by budding. They include the telomorphic ascomycetous yeasts which are found in a very wide range of habitats.Cloning, Molecular: 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.Macropodidae: A family of herbivorous leaping MAMMALS of Australia, New Guinea, and adjacent islands. Members include kangaroos, wallabies, quokkas, and wallaroos.Two-Hybrid System Techniques: 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.Chromosomes, Fungal: Structures within the nucleus of fungal cells consisting of or containing DNA, which carry genetic information essential to the cell.Caenorhabditis elegans: A species of nematode that is widely used in biological, biochemical, and genetic studies.Kinetics: The rate dynamics in chemical or physical systems.Signal Transduction: 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.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Cell Cycle Checkpoints: Regulatory signaling systems that control the progression through the CELL CYCLE. They ensure that the cell has completed, in the correct order and without mistakes, all the processes required to replicate the GENOME and CYTOPLASM, and divide them equally between two daughter cells. If cells sense they have not completed these processes or that the environment does not have the nutrients and growth hormones in place to proceed, then the cells are restrained (or "arrested") until the processes are completed and growth conditions are suitable.Dyneins: A family of multisubunit cytoskeletal motor proteins that use the energy of ATP hydrolysis to power a variety of cellular functions. Dyneins fall into two major classes based upon structural and functional criteria.Chromosomes, Human: Very long DNA molecules and associated proteins, HISTONES, and non-histone chromosomal proteins (CHROMOSOMAL PROTEINS, NON-HISTONE). Normally 46 chromosomes, including two sex chromosomes are found in the nucleus of human cells. They carry the hereditary information of the individual.Nondisjunction, Genetic: The failure of homologous CHROMOSOMES or CHROMATIDS to segregate during MITOSIS or MEIOSIS with the result that one daughter cell has both of a pair of parental chromosomes or chromatids and the other has none.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Escherichia coli: 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.Proteolysis: 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.Multiprotein Complexes: Macromolecular complexes formed from the association of defined protein subunits.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Gene Expression Regulation, Fungal: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in fungi.Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.Molecular Weight: The sum of the weight of all the atoms in a molecule.Phosphoprotein Phosphatases: A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)DNA-Binding Proteins: 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.Green Fluorescent Proteins: Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.Cell Nucleolus: Within most types of eukaryotic CELL NUCLEUS, a distinct region, not delimited by a membrane, in which some species of rRNA (RNA, RIBOSOMAL) are synthesized and assembled into ribonucleoprotein subunits of ribosomes. In the nucleolus rRNA is transcribed from a nucleolar organizer, i.e., a group of tandemly repeated chromosomal genes which encode rRNA and which are transcribed by RNA polymerase I. (Singleton & Sainsbury, Dictionary of Microbiology & Molecular Biology, 2d ed)Cells, Cultured: 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.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Proton-Translocating ATPases: Multisubunit enzymes that reversibly synthesize ADENOSINE TRIPHOSPHATE. They are coupled to the transport of protons across a membrane.Protein Phosphatase 2: A phosphoprotein phosphatase subtype that is comprised of a catalytic subunit and two different regulatory subunits. At least two genes encode isoforms of the protein phosphatase catalytic subunit, while several isoforms of regulatory subunits exist due to the presence of multiple genes and the alternative splicing of their mRNAs. Protein phosphatase 2 acts on a broad variety of cellular proteins and may play a role as a regulator of intracellular signaling processes.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.DNA, Catenated: CIRCULAR DNA that is interlaced together as links in a chain. It is used as an assay for the activity of DNA TOPOISOMERASES. Catenated DNA is attached loop to loop in contrast to CONCATENATED DNA which is attached end to end.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Potoroidae: A family of rat kangaroos found in and around Australia. Genera include Potorous and Bettongia.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Protein Tyrosine Phosphatases: An enzyme group that specifically dephosphorylates phosphotyrosyl residues in selected proteins. Together with PROTEIN-TYROSINE KINASE, it regulates tyrosine phosphorylation and dephosphorylation in cellular signal transduction and may play a role in cell growth control and carcinogenesis.Chromosomal Instability: An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation.Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.Dipodomys: A genus of the family Heteromyidae which contains 22 species. Their physiology is adapted for the conservation of water, and they seldom drink water. They are found in arid or desert habitats and travel by hopping on their hind limbs.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of CHROMOSOMES, chromosome pairs, or chromosome fragments. In a normally diploid cell (DIPLOIDY) the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is MONOSOMY (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is TRISOMY (symbol: 2N+1).Proteins: 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.Genes, Fungal: The functional hereditary units of FUNGI.Protein Transport: 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.Sister Chromatid Exchange: An exchange of segments between the sister chromatids of a chromosome, either between the sister chromatids of a meiotic tetrad or between the sister chromatids of a duplicated somatic chromosome. Its frequency is increased by ultraviolet and ionizing radiation and other mutagenic agents and is particularly high in BLOOM SYNDROME.Blotting, Western: 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.Microscopy, Video: Microscopy in which television cameras are used to brighten magnified images that are otherwise too dark to be seen with the naked eye. It is used frequently in TELEPATHOLOGY.Diptera: An order of the class Insecta. Wings, when present, number two and distinguish Diptera from other so-called flies, while the halteres, or reduced hindwings, separate Diptera from other insects with one pair of wings. The order includes the families Calliphoridae, Oestridae, Phoridae, SARCOPHAGIDAE, Scatophagidae, Sciaridae, SIMULIIDAE, Tabanidae, Therevidae, Trypetidae, CERATOPOGONIDAE; CHIRONOMIDAE; CULICIDAE; DROSOPHILIDAE; GLOSSINIDAE; MUSCIDAE; TEPHRITIDAE; and PSYCHODIDAE. The larval form of Diptera species are called maggots (see LARVA).PhosphoproteinsAdenosine Triphosphatases: A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.Luminescent Proteins: Proteins which are involved in the phenomenon of light emission in living systems. Included are the "enzymatic" and "non-enzymatic" types of system with or without the presence of oxygen or co-factors.Time Factors: Elements of limited time intervals, contributing to particular results or situations.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Drosophila melanogaster: A species of fruit fly much used in genetics because of the large size of its chromosomes.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Microinjections: The injection of very small amounts of fluid, often with the aid of a microscope and microsyringes.Cytoplasm: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.Transfection: 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.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Vaccines, Subunit: Vaccines consisting of one or more antigens that stimulate a strong immune response. They are purified from microorganisms or produced by recombinant DNA techniques, or they can be chemically synthesized peptides.Nuclear Matrix-Associated Proteins: A broad category of nuclear proteins that are components of or participate in the formation of the NUCLEAR MATRIX.beta Catenin: A multi-functional catenin that participates in CELL ADHESION and nuclear signaling. Beta catenin binds CADHERINS and helps link their cytoplasmic tails to the ACTIN in the CYTOSKELETON via ALPHA CATENIN. It also serves as a transcriptional co-activator and downstream component of WNT PROTEIN-mediated SIGNAL TRANSDUCTION PATHWAYS.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Chromatin: The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.Vacuolar Proton-Translocating ATPases: Proton-translocating ATPases that are involved in acidification of a variety of intracellular compartments.Salamandridae: A family of Urodela consisting of 15 living genera and about 42 species and occurring in North America, Europe, Asia, and North Africa.Xenopus laevis: The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.Intestinal Neoplasms: Tumors or cancer of the INTESTINES.Antigen-Presenting Cells: A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Precipitin Tests: Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.DNA, Fungal: Deoxyribonucleic acid that makes up the genetic material of fungi.Ovum: A mature haploid female germ cell extruded from the OVARY at OVULATION.Immunoblotting: 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.
Characterization of the DOC1/APC10 subunit of the yeast and the human anaphase-promoting complex. (1/7)
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)Identification of human APC10/Doc1 as a subunit of anaphase promoting complex. (2/7)
Anaphase-promoting complex or cyclosome (APC) is a ubiquitin ligase which specifically targets mitotic regulatory factors such as Pds1/Cut2 and cyclin B. Identification of the subunits of multiprotein complex APC in several species revealed the highly conserved composition of APC from yeast to human. It has been reported, however, that vertebrate APC is composed of at least eight subunits, APC1 to APC8, while budding yeast APC is constituted of at least 12 components, Apc1 to Apc13. It has not yet been clearly understood whether additional components found in budding yeast, Apc9 to Apc13, are actually composed of mammalian APC. Here we isolated and characterized human APC10/Doc1, and found that APC10/Doc1 binds to APC core subunits throughout the cell cycle. Further, it was found that APC10/Doc1 is localized in centrosomes and mitotic spindles throughout mitosis, while it is also localized in kinetochores from prophase to anaphase and in midbody in telophase and cytokinesis. These results strongly support the notion that human APC10/Doc1 may be one of the APC core subunits rather than the transiently associated regulatory factor. (+info)Doc1 mediates the activity of the anaphase-promoting complex by contributing to substrate recognition. (3/7)
The anaphase-promoting complex (APC) is a multisubunit E3 ubiquitin ligase that targets specific cell cycle-related proteins for degradation, regulating progression from metaphase to anaphase and exit from mitosis. The APC is regulated by binding of the coactivator proteins Cdc20p and Cdh1p, and by phosphorylation. We have developed a purification strategy that allowed us to purify the budding yeast APC to near homogeneity and identify two novel APC-associated proteins, Swm1p and Mnd2p. Using an in vitro ubiquitylation system and a native gel binding assay, we have characterized the properties of wild-type and mutant APC. We show that both the D and KEN boxes contribute to substrate recognition and that coactivator is required for substrate binding. APC lacking Apc9p or Doc1p/Apc10 have impaired E3 ligase activities. However, whereas Apc9p is required for structural stability and the incorporation of Cdc27p into the APC complex, Doc1p/Apc10 plays a specific role in substrate recognition by APC-coactivator complexes. These results imply that Doc1p/Apc10 may play a role to regulate the binding of specific substrates, similar to that of the coactivators. (+info)The APC subunit Doc1 promotes recognition of the substrate destruction box. (4/7)
BACKGROUND: Accurate chromosome segregation during mitosis requires the coordinated destruction of the mitotic regulators securin and cyclins. The anaphase-promoting complex (APC) is a multisubunit ubiquitin-protein ligase that catalyzes the polyubiquitination of these and other proteins and thereby promotes their destruction. How the APC recognizes its substrates is not well understood. In mitosis, the APC activator Cdc20 binds to the APC and is thought to recruit substrates by interacting with a conserved target protein motif called the destruction box. A related protein, called Cdh1, performs a similar function during G1. Recent evidence, however, suggests that the core APC subunit Doc1 also contributes to substrate recognition. RESULTS: To better understand the mechanism by which Doc1 promotes substrate binding to the APC, we generated a series of point mutations in Doc1 and analyzed their effects on the processivity of substrate ubiquitination. Mutations that reduce Doc1 function fall into two classes that define spatially and functionally distinct regions of the protein. One region, which includes the carboxy terminus, anchors Doc1 to the APC but does not influence substrate recognition. The other region, located on the opposite face of Doc1, is required for Doc1 to enhance substrate binding to the APC. Importantly, stimulation of binding by Doc1 also requires that the substrate contain an intact destruction box. Cells carrying DOC1 mutations that eliminate substrate recognition delay in mitosis with high levels of APC substrates. CONCLUSIONS: Doc1 contributes to recognition of the substrate destruction box by the APC. This function of Doc1 is necessary for efficient substrate proteolysis in vivo. (+info)Structures of APC/C(Cdh1) with substrates identify Cdh1 and Apc10 as the D-box co-receptor. (5/7)
(+info)Spindle assembly requires complete disassembly of spindle remnants from the previous cell cycle. (6/7)
(+info)A novel yeast screen for mitotic arrest mutants identifies DOC1, a new gene involved in cyclin proteolysis. (7/7)
B-type cyclins are rapidly degraded at the transition between metaphase and anaphase and their ubiquitin-mediated proteolysis is required for cells to exit mitosis. We used a novel enrichment to isolate new budding mutants that arrest the cell cycle in mitosis. Most of these mutants lie in the CDC16, CDC23, and CDC27 genes, which have already been shown to play a role in cyclin proteolysis and encode components of a 20S complex (called the cyclosome or anaphase promoting complex) that ubiquitinates mitotic cyclins. We show that mutations in CDC26 and a novel gene, DOC1, also prevent mitotic cyclin proteolysis. Mutants in either gene arrest as large budded cells with high levels of the major mitotic cyclin (Clb2) protein at 37 degrees C and cannot degrade Clb2 in G1-arrested cells. Cdc26 associates in vivo with Doc1, Cdc16, Cdc23, and Cdc27. In addition, the majority of Doc1 cosediments at 20S with Cdc27 in a sucrose gradient, indicating that Cdc26 and Doc1 are components of the anaphase promoting complex. (+info)
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ANTIGEN PRESENTATION AND ASSEMBLY BY MOUSE I-A(K) CLASS-II MOLECULES IN HUMAN APC CONTAINING DELETED OR MUTATED HLA DM GENES -...
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ANAPC71999). "Characterization of the DOC1/APC10 subunit of the yeast and the human anaphase-promoting complex". J. Biol. Chem. 274 ( ... This gene encodes a tetratricopeptide repeat containing component of the anaphase-promoting complex/cyclosome (APC/C), a large ... Anaphase-promoting complex subunit 7 is an enzyme that in humans is encoded by the ANAPC7 gene. Multiple transcript variants ... 2004). "TPR subunits of the anaphase-promoting complex mediate binding to the activator protein CDH1". Curr. Biol. 13 (17): ...
"Characterization of the DOC1/APC10 subunit of the yeast and the human anaphase-promoting complex". The Journal of Biological ... "Mammalian p55CDC mediates association of the spindle checkpoint protein Mad2 with the cyclosome/anaphase-promoting complex, and ... Vodermaier HC, Gieffers C, Maurer-Stroh S, Eisenhaber F, Peters JM (Sep 2003). "TPR subunits of the anaphase-promoting complex ... "TPR subunits of the anaphase-promoting complex mediate binding to the activator protein CDH1". Current Biology. 13 (17): 1459- ...
1999). "Characterization of the DOC1/APC10 subunit of the yeast and the human anaphase-promoting complex". J. Biol. Chem. 274 ( ... A large protein complex, termed the anaphase-promoting complex (APC), or the cyclosome, promotes metaphase-anaphase transition ... 2004). "TPR subunits of the anaphase-promoting complex mediate binding to the activator protein CDH1". Curr. Biol. 13 (17): ... Anaphase-promoting complex subunit 4 is an enzyme that in humans is encoded by the ANAPC4 gene. ...
"Characterization of the DOC1/APC10 subunit of the yeast and the human anaphase-promoting complex". The Journal of Biological ... "The Apc5 subunit of the anaphase-promoting complex/cyclosome interacts with poly(A) binding protein and represses internal ... "Crystal structure of the APC10/DOC1 subunit of the human anaphase-promoting complex". Nature Structural Biology. 8 (9): 784-8. ... "TPR subunits of the anaphase-promoting complex mediate binding to the activator protein CDH1". Current Biology. 13 (17): 1459- ...
2004). "The Arabidopsis anaphase-promoting complex or cyclosome: molecular and genetic characterization of the APC2 subunit". ... 1999). "Characterization of the DOC1/APC10 subunit of the yeast and the human anaphase-promoting complex". J. Biol. Chem. 274 ( ... A large protein complex, termed the anaphase-promoting complex (APC), or the cyclosome, promotes metaphase-anaphase transition ... 2004). "TPR subunits of the anaphase-promoting complex mediate binding to the activator protein CDH1". Curr. Biol. 13 (17): ...
Apc10/Doc1, has been shown to promote substrate binding by mediating their interactions with Cdh1 and Cdc20. The subunit Apc15 ... Anaphase-promoting complex (also called the cyclosome or APC/C) is an E3 ubiquitin ligase that marks target cell cycle proteins ... anaphase-promoting complex at the US National Library of Medicine Medical Subject Headings (MeSH) 3D electron microscopy ... Review) Harper JW, Burton JL, Solomon MJ (September 2002). "The anaphase-promoting complex: it's not just for mitosis any more ...
2004). "The Apc5 Subunit of the Anaphase-Promoting Complex/Cyclosome Interacts with Poly(A) Binding Protein and Represses ... 1999). "Characterization of the DOC1/APC10 subunit of the yeast and the human anaphase-promoting complex". J. Biol. Chem. 274 ( ... Anaphase-promoting complex subunit 5 is an enzyme that in humans is encoded by the ANAPC5 gene. The anaphase-promoting complex ... "The Apc5 Subunit of the Anaphase-Promoting Complex/Cyclosome Interacts with Poly(A) Binding Protein and Represses Internal ...
Open Access Journals... a highly potent inhibitor of the Anaphase Promoting Complex/Cyclosome (APC/C)-the E3 ubiquitin ligase essential for anaphase ... These efforts have culminated in recently reported structure models for human MCC:APC/C supra-complexes at near-atomic ... originates from defective kinetochore-microtubule interactions and leads to formation of the mitotic checkpoint complex (MCC), ... 2003) TPR subunits of the anaphase-promoting complex mediate binding to the activator protein CDH1. Curr Biol 13: 1459-1468. ...
aimspress.comStructure of the anaphase-promoting complex/cyclosome interacting with a mitotic checkpoint complex. Science 323, 1477-1481 ( ... across all 12 analyzed complexes. In 8 of these complexes (67%), one or two subunits per complex had a phosphorylation site ... Structures of APC/CCdh1 with substrates identify Cdh1 and Apc10 as the D-box co-receptor. Nature 470, 274-278 (2011).. ... The anaphase promoting complex/cyclosome: A machine designed to destroy. Nat. Rev. Mol. Cell Biol. 7, 644-656 (2006).. ...
Apc10 Subunit, Anaphase-Promoting Complex-Cyclosome. Subunidade Apc10 do Ciclossomo-Complexo Promotor de Anáfase. Subunidad ... Apc10 Subunit, Anaphase-Promoting Complex-Cyclosome. Subunidade Apc10 do Ciclossomo-Complexo Promotor de Anáfase. Subunidad ... Apc10 del Ciclosoma-Complejo Promotor de la Anafase. Apc11 Subunit, Anaphase-Promoting Complex-Cyclosome. Subunidade Apc11 do ... Apc10 del Ciclosoma-Complejo Promotor de la Anafase. Apc11 Subunit, Anaphase-Promoting Complex-Cyclosome. Subunidade Apc11 do ...
The APC/C E3 Ligase Complex Activator FZR1 Restricts BRAF Oncogenic Function | Cancer DiscoveryThe anaphase promoting complex/cyclosome: a machine designed to destroy. Nat Rev Mol Cell Biol 2006;7:644-56. ... Furthermore, depletion of other APC complex subunits, such as CDC27 or APC10, also resulted in BRAF accumulation and ERK ... The anaphase-promoting complex/cyclosome (APC/C): cell-cycle-dependent and -independent functions. Biochem Soc Trans 2010;38:65 ... The anaphase-promoting complex/cyclosome (APC/C, also named APC) ubiquitin E3 ligase is essential for cell-cycle progression ...
Structure of the mitotic checkpoint complex. - PubMed - NCBI... whose assembly is catalysed by unattached chromosomes and which binds and inhibits the anaphase-promoting complex/cyclosome ( ... and displacing Cdc20 to disrupt formation of a bipartite D-box receptor with the APC/C subunit Apc10. Mad2, in the closed ... Structure of the mitotic checkpoint complex.. Chao WC1, Kulkarni K, Zhang Z, Kong EH, Barford D. ... The MCC inhibits the APC/C by obstructing degron recognition sites on Cdc20 (the substrate recruitment subunit of the APC/C) ...
Protein Subunits - chemistry , Apc10 Subunit, Anaphase-Promoting Complex-Cyclosome - chemistry , Anaphase-Promoting Complex- ... Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome - chemistry , Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome - chemistry ... Apc11 Subunit, Anaphase-Promoting Complex-Cyclosome - metabolism , Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome - ... Apc7 Subunit, Anaphase-Promoting Complex-Cyclosome - chemistry , Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome - ...
anaphase-promoting complex (APC): the sum of its parts? | Biochemical Society Transactions | Portland PressOne APC subunit, Doc1/Apc10, contains a Doc domain. This domain is present in several other proteins containing ubiquitylation- ... The APC (anaphase-promoting complex) or cyclosome is a large multisubunit protein complex. It has 13 core components (with ... The anaphase-promoting complex (APC): the sum of its parts? L.A. Passmore L.A. Passmore ... The APC (anaphase-promoting complex) is a multisubunit E3 ubiquitin ligase that targets cell-cycle-related proteins for ...
Study of Cyclin Proteolysis in Anaphase-Promoting Complex (APC) Mutant Cells Reveals the Requirement for APC Function in the...1997) Distinct subunit functions and cell cycle regulated phosphorylation of 20S APC/cyclosome required for anaphase in fission ... 1998) Apc10 and Ste9/Srw1, two regulators of the APC-cyclosome, as well as the CDK inhibitor Rum1 are required for G1 cell- ... 1999) The Schizosaccharomyces pombe dim1(+) gene interacts with the anaphase-promoting complex or cyclosome (APC/C) component ... 1999) Whose end is destruction: cell division and the anaphase-promoting complex. Genes Dev. 13:2039-2058. ...
Ubiquitin-Protein Ligase Complexes/physiology*. Substances. *Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome ... APC10). (C) As (B) but displaying MCC and Nek2A binding after APC4 immunoprecipitation and normalization against APC4 levels. ... The Anaphase Promoting Complex/Cyclosome (APC/C) in complex with its co-activator Cdc20 is responsible for targeting proteins ... Nek2A and the mitotic checkpoint complex (MCC) have an overlap in APC/C subunit requirements for binding and we propose that ...
Plus itConversely, loss of these two proteins, as well as the APC10 subunit or the CCS52 anaphase-promoting complex or cyclosome ... two negative regulators of the anaphase-promoting complex or cyclosome, results in the expression of the defense marker gene ... This is achieved through their incorporation into a protein complex called the RNA-induced silencing complex (RISC; Czech and ... 2017). Tudor-SN-mediated endonucleolytic decay of human cell microRNAs promotes G1/S phase transition. Science 862: 859-862. ...
The RIO protein kinase-encoding gene Sj-riok-2 is involved in key reproductive processes in Schistosoma japonicum | Parasites &...Crystal structure of the APC10/DOC1 subunit of the human anaphase-promoting complex. Nat Struct Biol. 2001;8:784-8.View Article ... In the cell cycle, the activation of anaphase-promoting complex or cyclosome (APC/C), a conserved multi-subunit E3 ubiquitin ( ... Identification of a cullin homology region in a subunit of the anaphase-promoting complex. Science. 1998;279:1219-22.View ... Mass spectrometric analysis of the anaphase-promoting complex from yeast: identification of a subunit related to cullins. ...
Gene ID: 64682 | ANAPC10 Antibody ResourceANAPC10 is a core subunit of the anaphase-promoting complex (APC), or cyclosome, a ubiquitin protein ligase that is essential ... anaphase-promoting complex subunit 10. Nucleotide: NM_001256708. Alias: DOC1;APC10;. Ensembl: ... Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls ... The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the ...
RCSB PDB - Protein Feature View
- Anaphase-promoting complex subunit 16 - Q96DE5 (APC16 HUMAN)... and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon ... Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls ... ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined ... Subunit Structure. The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5 ...
Anti-APC10(A95-363R) - SignalChem Online StoreRecognizes the APC10 protein Cited Applications :WB, ELISA, IF, IHC Cross Reactivity :Human, Mouse and Rat Host / Isotype / ... Clone# :Rabbit, IgG Immunogen :APC10 antibody was raise ... 1. Peters JM: The anaphase promoting complex/cyclosome: a ... 2. Jorgensen PM et al: Characterisation of the human APC1, the largest subunit of the anaphase-promoting complex. Gene2001; 262 ... 3. Passmore LA et al: Doc1 mediates the activity of the anaphase-promoting complex by contributing to substrate recognition. ...
APC16 is a conserved subunit of the anaphase-promoting complex/cyclosome | Journal of Cell Science... the small subunit APC10 may be involved in APC/C processivity and/or substrate recognition (Carroll and Morgan, 2002; ... APC16 is a conserved subunit of the anaphase-promoting complex/cyclosome. Geert J. P. L. Kops, Monique van der Voet, Michael S ... APC16 is a conserved subunit of the anaphase-promoting complex/cyclosome. Geert J. P. L. Kops, Monique van der Voet, Michael S ... APC16 is a conserved subunit of the anaphase-promoting complex/cyclosome. Geert J. P. L. Kops, Monique van der Voet, Michael S ...
Mitotic regulation of the human anaphase‐promoting complex by phosphorylation | The EMBO JournalDistinct subunit functions and cell cycle regulated phosphorylation of 20S APC/cyclosome required for anaphase in fission yeast ... No peptides from the small subunits Apc10, Apc11 and Cdc26 were recovered. Cdc20 peptides were only found in mitotic APC ... The anaphase‐promoting complex (APC) or cyclosome is a ubiquitin ligase that initiates anaphase and mitotic exit. APC ... Geley S, Kramer E, Gieffers C, Gannon J, Peters JM and Hunt T (2001) Anaphase‐promoting complex/cyclosome‐dependent proteolysis ...
APC:Cdc20 Mediated Degradation Of Cell Cycle Proteins Prior To Satisfation Of The Cell Cycle Checkpoint Pathway | MyBioSourceCyclosome subunit 10; DKFZP564L0562; Human ANAPC10; anaphase-promoting complex subunit 10 isoform 1; anaphase promoting complex ... Anti-ANAPC10 / APC10 Antibody (aa10-20) IHC-plus; Cyclosome subunit 10; DKFZP564L0562; Human ANAPC10; anaphase-promoting ... Anaphase promoting complex subunit 11 (yeast APC11 homolog); Anaphase promoting complex subunit 11; Anaphase promoting complex ... Cyclosome subunit 1; Mitotic checkpoint regulator; Human ANAPC1; anaphase-promoting complex subunit 1; anaphase promoting ...
Structural analysis of human Cdc20 supports multisite degron recognition by APC/C | PNASThe anaphase-promoting complex/cyclosome (APC/C) promotes anaphase onset and mitotic exit through ubiquitinating securin and ... Biochemical and biophysical studies have established that Cdh1 and the APC/C subunit Apc10 serve as coreceptors for the D box, ... 2009) Structure of the anaphase-promoting complex/cyclosome interacting with a mitotic checkpoint complex. Science 323(5920): ... 2006) The anaphase promoting complex/cyclosome: A machine designed to destroy. Nat Rev Mol Cell Biol 7(9):644-656. ...
Bra008327 protein (Brassica rapa) - STRING interaction network... anaphase-promoting complex, subunit 10 family / APC10 family ; Component of the anaphase promoting complex/cyclosome (APC/C), a ... anaphase-promoting complex, subunit 10 family / APC10 family ; Component of the anaphase promoting complex/cyclosome (APC/C), a ... anaphase-promoting complex, subunit 10 family / APC10 family ; Component of the anaphase promoting complex/cyclosome (APC/C), a ... Known metabolic pathways, protein complexes, signal transduction pathways, etc ... from curated databases. ...
humchr04.txtAPC10_HUMAN 613745 Anaphase-promoting complex subunit 10 (APC10) (Cyclosome subunit 10) [APC10] ANAPC4 4p15.2 Q9UJX5 APC4_HUMAN ... 606947 Anaphase-promoting complex subunit 4 (APC4) (Cyclosome subunit 4) [APC4] ANK2 4q25-q27 Q01484 ANK2_HUMAN 106410 Ankyrin- ... PP2A subunit B isoform B55-gamma) (PP2A subunit B isoform PR55-gamma) (PP2A subunit B isoform R2-gamma) (PP2A subunit B isoform ... HUMAN 616008 COP9 signalosome complex subunit 4 (SGN4) (Signalosome subunit 4) (JAB1-containing signalosome subunit 4) [CSN4] ...
We exemplified this trend on the anaphase promoting complex (APC) where a core is highly conserved throughout all metazoans, ... They do not act alone but are organised in complexes. Throughout the life of a cell, complexes are dynamic in their composition ... Focussing on human protein complexes, we based our analysis on a manually curated dataset from HPRD. In total, 1,060 complexes ... of all complexes affected). Still, loss of whole complexes happened rarely. This biological signal deviated significantly from ...
Figure EV1. Anaphase‐promoting complex/cyclosome (APC/C) subunits across 90 eukaryotic lineages. Presences and absences (" ... and we calculated the percentage of present APC/C proteins in species having the main APC/C enzyme Apc10. Loss frequencies were ... we also included proteins that constitute the anaphase‐promoting complex/cyclosome (APC/C), which is targeted by kinetochore ... The phylogenomic analysis of the anaphase promoting complex and its targets points to complex and modern‐like control of the ...
Interactive Fly, DrosophilaThe anaphase-promoting complex or cyclosome (APC) is an unusually complicated ubiquitin ligase, composed of 13 core subunits ... and Doc1/Apc10, and another that contains the three TPR subunits (Cdc27, Cdc16, and Cdc23). The three TPR subunits display a ... Microinjection of antibodies against subunits of the anaphase-promoting complex/cyclosome or against human Cdc20 (fizzy) ... one of the substrate-targeting subunits of the anaphase-promoting complex (APC). However, Cdh1, another targeting subunit used ...
1999). "Characterization of the DOC1/APC10 subunit of the yeast and the human anaphase-promoting complex". J. Biol. Chem. 274 ( ... This gene encodes a tetratricopeptide repeat containing component of the anaphase-promoting complex/cyclosome (APC/C), a large ... Anaphase-promoting complex subunit 7 is an enzyme that in humans is encoded by the ANAPC7 gene. Multiple transcript variants ... 2004). "TPR subunits of the anaphase-promoting complex mediate binding to the activator protein CDH1". Curr. Biol. 13 (17): ...
"Characterization of the DOC1/APC10 subunit of the yeast and the human anaphase-promoting complex". The Journal of Biological ... "Mammalian p55CDC mediates association of the spindle checkpoint protein Mad2 with the cyclosome/anaphase-promoting complex, and ... Vodermaier HC, Gieffers C, Maurer-Stroh S, Eisenhaber F, Peters JM (Sep 2003). "TPR subunits of the anaphase-promoting complex ... "TPR subunits of the anaphase-promoting complex mediate binding to the activator protein CDH1". Current Biology. 13 (17): 1459- ...
UbiquitinCDC20Cdh1DOC1YeastPeters JMInhibitorMAD2DegradationProteolysisSister chromatidOnsetAPC16KinetochoresCDC27SaccharomycesMitosisMultisubunitPhosphorylationLarge complexesGeneProteins1998AffinitySpecificityStructuralInitiationHPRDKinaseAntibodySchizosaccharomyces1999Highly conservedDistinctRecruitmentCellCompositionFunctionsStable
- The signaling of the checkpoint originates from defective kinetochore-microtubule interactions and leads to formation of the mitotic checkpoint complex (MCC), a highly potent inhibitor of the Anaphase Promoting Complex/Cyclosome (APC/C)-the E3 ubiquitin ligase essential for anaphase onset. (aimspress.com)
- 1995) The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis. (aimspress.com)
- 1995) A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B. Cell 81: 279-288. (aimspress.com)
- The SAC is imposed by the mitotic checkpoint complex (MCC), whose assembly is catalysed by unattached chromosomes and which binds and inhibits the anaphase-promoting complex/cyclosome (APC/C), the E3 ubiquitin ligase that initiates chromosome segregation. (nih.gov)
- The APC (anaphase-promoting complex) is a multisubunit E3 ubiquitin ligase that targets cell-cycle-related proteins for degradation by the 26 S proteasome. (portlandpress.com)
- It is not known why the APC contains 13 subunits when many other ubiquitin ligases are small single-subunit enzymes. (portlandpress.com)
- The Anaphase Promoting Complex/Cyclosome (APC/C) in complex with its co-activator Cdc20 is responsible for targeting proteins for ubiquitin-mediated degradation during mitosis. (nih.gov)
- ANAPC10 is a core subunit of the anaphase-promoting complex (APC), or cyclosome, a ubiquitin protein ligase that is essential for progression through the cell cycle. (avivasysbio.com)
- Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. (avivasysbio.com)
- Error-free chromosome segregation depends on timely activation of the multi-subunit E3 ubiquitin ligase APC/C. Activation of the APC/C initiates chromosome segregation and mitotic exit by targeting critical cell-cycle regulators for destruction. (biologists.org)
- One of the machineries that promotes protein destruction is the E3 ubiquitin ligase anaphase-promoting complex/cyclosome or APC/C ( Peters, 2006 ). (biologists.org)
- The anaphase‐promoting complex (APC) or cyclosome is a ubiquitin ligase that initiates anaphase and mitotic exit. (embopress.org)
- The anaphase-promoting complex/cyclosome (APC/C) is a multisubunit ubiquitin ligase that mediates the ubiquitination of a multitude of substrates to drive cell cycle progression ( 1 ⇓ - 3 ). (pnas.org)
- Proteolysis of mitotic cyclins depends on a multisubunit ubiquitin-protein ligase, the anaphase promoting complex (APC). (sdbonline.org)
- Ubiquitin-mediated proteolysis due to the anaphase-promoting complex/cyclosome is essential for separation of sister chromatids, requiring degradation of the anaphase inhibitor Pds1, and for exit from mitosis, requiring inactivation of cyclin B Cdk1 kinases. (sdbonline.org)
- 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). (sdbonline.org)
- This gene encodes a tetratricopeptide repeat containing component of the anaphase-promoting complex/cyclosome (APC/C), a large E3 ubiquitin ligase that controls cell cycle progression by targeting a number of cell cycle regulators such as B-type cyclins for 26S proteasome-mediated degradation through ubiquitination. (wikipedia.org)
- This gene encodes a component protein of the APC complex, which is composed of eight proteins and functions as a protein ubiquitin ligase. (wikipedia.org)
- 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. (biologists.org)
- 13. Fang G, Yu H, Kirschner MW (1998) The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation. (aimspress.com)
- 14. Sudakin V, Chan GK, Yen TJ (2001) Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2. (aimspress.com)
- Here, using the crystal structure of Schizosaccharomyces pombe MCC (a complex of mitotic spindle assembly checkpoint proteins Mad2, Mad3 and APC/C co-activator protein Cdc20), we reveal the molecular basis of MCC-mediated APC/C inhibition and the regulation of MCC assembly. (nih.gov)
- The MCC inhibits the APC/C by obstructing degron recognition sites on Cdc20 (the substrate recruitment subunit of the APC/C) and displacing Cdc20 to disrupt formation of a bipartite D-box receptor with the APC/C subunit Apc10. (nih.gov)
- Mad2, in the closed conformation (C-Mad2), stabilizes the complex by optimally positioning the Mad3 KEN-box degron to bind Cdc20. (nih.gov)
- Mechanisms controlling the temporal degradation of Nek2A and Kif18A by the APC/C-Cdc20 complex. (nih.gov)
- We find that dimerization via the leucine zipper, in combination with the MR motif, is required for stable Nek2A binding to and ubiquitination by the APC/C. Nek2A and the mitotic checkpoint complex (MCC) have an overlap in APC/C subunit requirements for binding and we propose that Nek2A binds with high affinity to apo-APC/C and is degraded by the pool of Cdc20 that avoids inhibition by the SAC. (nih.gov)
- Kif18A is ubiquitinated by the APC/C-Cdc20 complex. (nih.gov)
- At the metaphase-anaphase transition, APC/C in complex with its mitotic activator Cdc20 (APC/C Cdc20 ) ubiquitinates securin and cyclin B1, triggering their destruction to allow separase activation and cohesin cleavage. (pnas.org)
- In anaphase, APC/C bound to the Cdc20 homolog Cdh1 (APC/C Cdh1 ) further mediate the ubiquitination of cyclin B1 and other mitotic regulators, resulting in their degradation and mitotic exit. (pnas.org)
- consisting of BubR1/Mad3, Bub3, Mad2, and Cdc20) anchors Cdc20 at a site on APC/C that is different from the site bound by free Cdc20, presumably blocking the productive engagement of the D box with Cdc20 and Apc10 ( 16 ⇓ ⇓ ⇓ ⇓ - 21 ). (pnas.org)
- Activation of the APC requires its association with substoichiometric activating subunits termed Cdc20 and Hct1 (also known as Cdh1). (sdbonline.org)
- In budding yeast, APC/C(Cdc20) promotes the degradation of the Pds1p anaphase inhibitor at the metaphase-to-anaphase transition, whereas APC/C(Cdh1) promotes the degradation of the mitotic cyclins at the exit from mitosis. (sdbonline.org)
- Nek2 isoform A (Nek2A) is a presumed substrate of the anaphase‐promoting complex/cyclosome containing Cdc20 (APC/C Cdc20 ). (biologists.org)
- At the point in the cell cycle when APC/C Cdc20 complexes are formed, however, the spindle checkpoint also becomes active and blocks Cdc20. (biologists.org)
- Biochemical and biophysical studies have established that Cdh1 and the APC/C subunit Apc10 serve as coreceptors for the D box, with the D box bridging an interaction between the two ( 7 ⇓ ⇓ ⇓ - 11 ). (pnas.org)
- Both processes require the Cdc14 phosphatase, whose release from the nucleolus during anaphase causes dephosphorylation and thereby activation of Cdh1 and accumulation of another protein, Sic1. (sdbonline.org)
- 3. Passmore LA et al: Doc1 mediates the activity of the anaphase-promoting complex by contributing to substrate recognition. (signalchem.com)
- 9. Funabiki H, Kumada K, Yanagida M (1996) Fission yeast Cut1 and Cut2 are essential for sister chromatid separation, concentrate along the metaphase spindle and form large complexes. (aimspress.com)
- 16. Millband DN, Hardwick KG (2002) Fission yeast Mad3p is required for Mad2p to inhibit the anaphase-promoting complex and localizes to kinetochores in a Bub1p-, Bub3p-, and Mph1p-dependent manner. (aimspress.com)
- 1. Peters JM: The anaphase promoting complex/cyclosome: a machine designed to destroy. (signalchem.com)
- 1996) Anaphase initiation in Saccharomyces cerevisiae is controlled by the APC-dependent degradation of the anaphase inhibitor Pds1p. (aimspress.com)
- This activity of Pds1p is independent of its activity as an anaphase inhibitor. (sdbonline.org)
- It is proposed that the dual role of Pds1p as an inhibitor of anaphase and of cyclin degradation allows the cell to couple the exit from mitosis to the prior completion of anaphase. (sdbonline.org)
- 1997) MAD2 associates with the cyclosome/anaphase-promoting complex and inhibits its activity. (aimspress.com)
- However in contrast to Nek2A, Kif18A is not degraded until anaphase showing that additional mechanisms contribute to Nek2A degradation. (nih.gov)
- The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. (avivasysbio.com)
- Progression through mitosis is controlled by protein degradation that is mediated by the anaphase-promoting complex/cyclosome and its associated specificity factors. (sdbonline.org)
- The APC complex is a cyclin degradation system that governs exit from mitosis. (wikipedia.org)
- First, enhancing mitotic checkpoint complex (MCC) formation by nocodazole treatment inhibited the degradation of geminin and cyclin A, whereas Nek2A disappeared at a normal rate. (biologists.org)
- Proteolysis commences during anaphase, persisting throughout G1 until it is terminated by cyclin-dependent kinases (CDKs) as cells enter S phase. (sdbonline.org)
- The proteolytic events triggered by the APC are required to release sister chromatid cohesion during anaphase, to control the exit from mitosis and to prevent premature entry into S-phase. (portlandpress.com)
- The anaphase-promoting complex/cyclosome (APC/C) promotes anaphase onset and mitotic exit through ubiquitinating securin and cyclin B1. (pnas.org)
- We now report the identification and characterization of APC16, a conserved subunit of the APC/C. APC16 was found in association with tandem-affinity-purified mitotic checkpoint complex protein complexes. (biologists.org)
- APC16 is a bona fide subunit of human APC/C: it is present in APC/C complexes throughout the cell cycle, the phenotype of APC16-depleted cells copies depletion of other APC/C subunits, and APC16 is important for APC/C activity towards mitotic substrates. (biologists.org)
- The resulting ortholog sets imply that the last eukaryotic common ancestor ( LECA ) possessed a complex kinetochore and highlight that current‐day kinetochores differ substantially. (embopress.org)
- Recently, it has been shown that cyclin A destruction early in mitosis is necessary for progressive stabilization of the mitotic spindle, promoting proper attachments to kinetochores and formation of the metaphase plate ( Kabeche and Compton, 2013 ). (biologists.org)
- Of these, 32 sites are clustered in parts of Apc1 and the tetratricopeptide repeat (TPR) subunits Cdc27, Cdc16, Cdc23 and Apc7. (embopress.org)
- This protein and two other APC complex proteins, CDC23 and CDC27, contain a tetratricopeptide repeat (TPR), a protein domain that may be involved in protein-protein interaction. (wikipedia.org)
- This study explores the molecular function and regulation of the APC regulatory subunit Hct1 in Saccharomyces cerevisiae . (sdbonline.org)
- Progression through mitosis depends on a large number of protein complexes that regulate the major structural and physiological changes necessary for faithful chromosome segregation. (sciencemag.org)
- The APC (anaphase-promoting complex) or cyclosome is a large multisubunit protein complex. (portlandpress.com)
- The APC contains at least 13 subunits and is regulated by the binding of co-activator proteins and by phosphorylation. (portlandpress.com)
- Purified Hct1 is phosphorylated in vitro at these sites by purified Cdc28-cyclin complexes, and phosphorylation abolishes the ability of Hct1 to activate the APC in vitro. (sdbonline.org)
- The large complexes involved in transcription (polymerases and transcription factors) and translation (ribosomes) must be tightly regulated to allow the control of gene expression. (portlandpress.com)
- Anaphase-promoting complex subunit 7 is an enzyme that in humans is encoded by the ANAPC7 gene. (wikipedia.org)
- Most cellular proteins form a complex network of interactions with other proteins and many are components of large multiprotein complexes [ 1 - 3 ]. (portlandpress.com)
- Here, the complexes are connected by shared components, e.g. proteins present in more than one complex. (beds.ac.uk)
- Some of these attachments, which can consist of multiple proteins itself, can be connected to different core complexes. (beds.ac.uk)
- These co‐evolutionary patterns improve our understanding of kinetochore function and evolution, which we illustrated with the RZZ complex, TRIP 13, the MCC , and some nuclear pore proteins. (embopress.org)
- The mutual inhibition between APC and CDKs explains how cells suppress mitotic CDK activity during G1 and then establish a period with elevated kinase activity from S phase until anaphase (Zachariae, 1998). (sdbonline.org)
- A ) The APC/C complex was affinity purified using an APC4 antibody from nocodazole-arrested cells or cells released from nocodazole into MG132 for 2 h. (nih.gov)
- Although the activity and specificity of E3s such as the APC are crucial, most E3s exist as much smaller, often single-subunit, enzymes. (portlandpress.com)
- Thus, protein complexes contain not only structural and functional, but also evolutionary cores. (beds.ac.uk)
- This complexity, comprising both the functional and structural entities of protein complexes, raises the question how the interplay of core complexes with variable attachments evolved. (beds.ac.uk)
- Focussing on human protein complexes, we based our analysis on a manually curated dataset from HPRD. (beds.ac.uk)
- C ) Stable HeLa cell lines expressing FLAG-tagged Kif18A or Kif18AΔLR were arrested with nocodazole and the APC/C complex purified using an APC4 antibody. (nih.gov)
- Western blot analysis of APC10 in mouse heart tissue lysate with APC10 antibody at (A) 1 and (B) 2 ug/mL. (signalchem.com)
- Immunohistochemistry of APC10 in mouse heart tissue with APC10 antibody at 5 ug/mL. (signalchem.com)
- An apparent exception to this relationship is found in Schizosaccharomyces pombe mutants with mutations of the anaphase-promoting complex (APC). (asm.org)
- Following anaphase, dephosphorylation of Hct1 by Cdc14 may help initiate cyclin destruction (Jaspersen, 1999). (sdbonline.org)
- We exemplified this trend on the anaphase promoting complex (APC) where a core is highly conserved throughout all metazoans, but flexibility in certain components is observable. (beds.ac.uk)
- Each component protein of the APC complex is highly conserved among eukaryotic organisms. (wikipedia.org)
- Here, we analysed in a large scale approach whether this flexibility in evolution is only limited to a distinct number of complexes or represents a more general trend. (beds.ac.uk)
- Consecutive additions and losses of distinct units is a fundamental process in the evolution of protein complexes. (beds.ac.uk)
- Throughout the life of a cell, complexes are dynamic in their composition due to attachments and shared components. (beds.ac.uk)
- In this review, I discuss the composition of the APC and the functions of its subunits with the goal of gaining insight into the mechanism of the APC as a whole. (portlandpress.com)
- We computed interologs in 25 different species and predicted the composition of complexes. (beds.ac.uk)
- Over the analysed species, the composition of most complexes was highly flexible and only 25% of all genes were never lost. (beds.ac.uk)
- In the present study, the structures and functions of individual APC subunits are discussed. (portlandpress.com)
- By adding different attachments, isoforms of a complex are built, possibly with slightly different functions. (beds.ac.uk)
- Why do large stable multiprotein complexes exist? (portlandpress.com)