The phase of cell nucleus division following METAPHASE, in which the CHROMATIDS separate and migrate to opposite poles of the spindle.
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.
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).
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 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.
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.
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.
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 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.
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 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.
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.
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.
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.
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 widely-expressed cyclin A subtype that functions during the G1/S and G2/M transitions of the CELL CYCLE.
The cellular signaling system that halts the progression of cells through MITOSIS or MEIOSIS if a defect that will affect CHROMOSOME SEGREGATION is detected.
The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS.
A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.
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.
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 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.
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 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.
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.
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.
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.
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 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.
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.
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.
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.
A genus of ascomycetous fungi of the family Schizosaccharomycetaceae, order Schizosaccharomycetales.
Nocodazole is an antineoplastic agent which exerts its effect by depolymerizing microtubules.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
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.
Proteins found in any species of fungus.
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.
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.
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.
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)
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.
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.
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.
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.
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 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).
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.
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.
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).
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 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.
Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle.
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.
An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.
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 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.
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)
The process by which the CYTOPLASM of a cell is divided.
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.
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 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.
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.
Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.
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.
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.
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.
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 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.
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.
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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
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.
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.
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.
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.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
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.
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.
The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.
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.
Transport proteins that carry specific substances in the blood or across cell membranes.
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.
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.
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.
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.-.
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.
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.
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.
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.
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.
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.
Established cell cultures that have the potential to propagate indefinitely.
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).
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.
A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.
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.
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).
A family of herbivorous leaping MAMMALS of Australia, New Guinea, and adjacent islands. Members include kangaroos, wallabies, quokkas, and wallaroos.
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.
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.
The developmental entity of a fertilized egg (ZYGOTE) in animal species other than MAMMALS. For chickens, use CHICK EMBRYO.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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)
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.
A cell line derived from cultured tumor cells.
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.
Structures within the nucleus of fungal cells consisting of or containing DNA, which carry genetic information essential to the cell.
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.
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.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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.
A species of nematode that is widely used in biological, biochemical, and genetic studies.
A family of rat kangaroos found in and around Australia. Genera include Potorous and Bettongia.
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.
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)
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.
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.
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.
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).
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in fungi.
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).
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.
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.
An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.
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.
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.
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.
A family of Urodela consisting of 15 living genera and about 42 species and occurring in North America, Europe, Asia, and North Africa.

SWM1, a developmentally regulated gene, is required for spore wall assembly in Saccharomyces cerevisiae. (1/853)

Meiosis in Saccharomyces cerevisiae is followed by encapsulation of haploid nuclei within multilayered spore walls. Formation of this spore-specific wall requires the coordinated activity of enzymes involved in the biosynthesis of its components. Completion of late events in the sporulation program, leading to spore wall formation, requires the SWM1 gene. SWM1 is expressed at low levels during vegetative growth but its transcription is strongly induced under sporulating conditions, with kinetics similar to those of middle sporulation-specific genes. Homozygous swm1Delta diploids proceed normally through both meiotic divisions but fail to produce mature asci. Consistent with this finding, swm1Delta mutant asci display enhanced sensitivity to enzymatic digestion and heat shock. Deletion of SWM1 specifically affects the expression of mid-late and late sporulation-specific genes. All of the phenotypes observed are similar to those found for the deletion of SPS1 or SMK1, two putative components of a sporulation-specific MAP kinase cascade. However, epistasis analyses indicate that Swm1p does not form part of the Sps1p-Smk1p-MAP kinase pathway. We propose that Swm1p, a nuclear protein, would participate in a different signal transduction pathway that is also required for the coordination of the biochemical and morphological events occurring during the last phase of the sporulation program.  (+info)

Inhibitory phosphorylation of the APC regulator Hct1 is controlled by the kinase Cdc28 and the phosphatase Cdc14. (2/853)

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. (3/853)

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. (4/853)

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. (5/853)

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. (6/853)

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. (7/853)

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. (8/853)

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)

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
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. ...
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 ...
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 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.
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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. ...
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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: ...
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 ...
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 ...
1GQP: Implications for the Ubiquitination Reaction of the Anaphase-Promoting Complex from the Crystal Structure of the Doc1/Apc10 Subunit.
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 ...
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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.
Components of the SAC include the Mad1, Mad2, BubR1 (Mad3) and Bub3 proteins and the Bub1, Mps1 (Mph1) and Aurora-B kinases. When individual kinetochores are not bound to spindle microtubules checkpoint proteins are recruited to the unattached kinetochore and the SAC is activated. Kinetochore association of Mad2 induces a conformational change which allows it to bind Mad3 and Cdc20 to form a potent inhibitor, the mitotic checkpoint complex (MCC), which inhibits the anaphase-promoting complex/cyclosome (APC/C), a specialized E3 ubiquitin ligase. When the checkpoint is satisfied the spindle checkpoint signal is silenced and the Cdc20-APC/C is activated. This triggers the poly-ubiquitination of securin and cyclin, which allows the dissolution of sister chromatid cohesion and mitotic progression1 London N, Biggins S. Signaling dynamics in the spindle checkpoint response. Nat Rev Mol Cell Biol 2014; 15:736-47; PMID:25303117; http://dx.doi.org/10.1038/ ...
Accurate chromosomal segregation is monitored by the mitotic checkpoint, and an increased rate of chromosomal missegregation leads to chromosomal instability (CIN). Here, we demonstrate that the HBV X protein (HBx) binds BubR1, a component of the mitotic checkpoint complex and co-localizes with BubR1 at the kinetochores. HBx binding to BubR1 attenuates the association between BubR1 and CDC20, an activator of the anaphase-promoting complex/cyclosome (APC/C) and induces slippage of mitotic arrest in the presence of microtubule poisons. In addition, HBx binding to BubR1 results in the accumulation of lagging chromosomes and chromosome bridges. In contrast, a C-terminally truncated HBx mutant (HBx(1-100)) fails to bind BubR1 and does not cause aberrant chromosomal segregation. This provides a novel mechanism for dysregulation of the mitotic checkpoint by a viral pathogen linking it to the accumulation of chromosomal instability in HBV-associated hepatocarcinogenesis.. ...
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 ...
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 ...
The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase ...
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
The anaphase-promoting complex or cyclosome with the subunit Cdh1 (APC/CCdh1) is an E3 ubiquitin ligase involved in the control of the cell cycle. Here, we identified sporadic mutations occurring in the genes encoding APC components, including Cdh1, in human melanoma samples and found that loss of APC/CCdh1 may promote melanoma development and progression, but not by affecting cell cycle regulatory targets of APC/C. Most of the mutations we found in CDH1 were those associated with ultraviolet light (UV)-induced melanomagenesis. Compared with normal human skin tissue and human or mouse melanocytes, the abundance of Cdh1 was decreased and that of the transcription factor PAX3 was increased in human melanoma tissue and human or mouse melanoma cell lines, respectively; Cdh1 abundance was further decreased with advanced stages of human melanoma. PAX3 was a substrate of APC/CCdh1 in melanocytes, and APC/CCdh1-mediated ubiquitylation marked PAX3 for proteolytic degradation in a manner dependent on the ...
The anaphase-promoting complex/cyclosome (APC/C) is a ubiquitin ligase with essential functions in mitosis, meiosis, and G1 phase of the cell cycle. APC/C recognizes substrates via coactivator proteins such as Cdh1, and bound substrates are ubiquitinated by E2 enzymes that interact with a hetero-dimer of the RING subunit Apc11 and the cullin Apc2. We have obtained three-dimensional (3D) models of human and Xenopus APC/C by angular reconstitution and random conical tilt (RCT) analyses of negatively stained cryo-electron microscopy (cryo-EM) preparations, have determined the masses of these particles by scanning transmission electron microscopy (STEM), and have mapped the locations of Cdh1 and Apc2. These proteins are located on the same side of the asymmetric APC/C, implying that this is where substrates are ubiquitinated. We have further identified a large flexible domain in APC/C that adopts a different orientation upon Cdh1 binding. Cdh1 may thus activate APC/C both by recruiting substrates ...
ORDERED temporal degradation of proteins is an important regulatory mechanism that controls progression through the eukaryotic cell cycle (Reed 2006). The anaphase promoting complex/cyclosome (APC/C) is the E3 subunit of an ubiquitin-conjugating enzyme composed of at least thirteen subunits that targets proteins for proteolysis during the cell cycle (Peters 2006). APC/C function is critical for progression through mitosis where it degrades Pds1 (securin in higher eukaryotic cells) and other substrates to promote anaphase and the exit from mitosis (Pines 2006). APC/C cofactors Cdc20 and Cdh1 are important for conferring substrate specificity during different stages in the cell cycle (Peters 2006). It is unclear, however, how the APC/C chooses substrates for ubiquitylation and the specific role of each subunit in this process (Acquaviva and Pines 2006). The spindle assembly checkpoint (SAC) ensures the formation of a bipolar spindle and proper attachment of kinetochores (Lew and Burke 2003). The ...
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.
CDC27 is a core component of the anaphase-promoting complex/cyclosome (APC/C), a multisubunit E3 ubiquitin ligase, whose oscillatory activity is responsible for the metaphase-to-anaphase transition and mitotic exit. Here, in normal murine mammary gland epithelial cells (NMuMG), CDC27 expression is controlled posttranscriptionally through the RNA binding protein poly(rC) binding protein 1 (PCBP1)/heterogeneous nuclear ribonucleoprotein E1 (HNRNP E1). shRNA-mediated knockdown of HNRNP E1 abrogates translational silencing of the Cdc27 transcript, resulting in constitutive expression of CDC27. Dysregulated expression of CDC27 leads to premature activation of the G2-M-APC/C-CDC20 complex, resulting in the aberrant degradation of FZR1/CDH1, a cofactor of the G1 and late G2-M-APC/C and a substrate normally reserved for the SCF-βTRCP ligase. Loss of CDH1 expression and of APC/C-CDH1 activity, upon constitutive expression of CDC27, results in mitotic aberrations and aneuploidy in NMuMG cells. ...
LOCUS NP_001131136 537 aa linear PRI 20-JUN-2020 DEFINITION anaphase-promoting complex subunit 7 isoform b [Homo sapiens]. ACCESSION NP_001131136 VERSION NP_001131136.1 DBSOURCE REFSEQ: accession NM_001137664.1 KEYWORDS RefSeq. SOURCE Homo sapiens (human) ORGANISM Homo sapiens Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. REFERENCE 1 (residues 1 to 537) AUTHORS Wild T, Budzowska M, Hellmuth S, Eibes S, Karemore G, Barisic M, Stemmann O and Choudhary C. TITLE Deletion of APC7 or APC16 Allows Proliferation of Human Cells without the Spindle Assembly Checkpoint JOURNAL Cell Rep 25 (9), 2317-2328 (2018) PUBMED 30485802 REMARK GeneRIF: the contribution of the anaphase-promoting complex/cyclosome subunits APC7 and APC16 to APC/C composition and function in human cells. REFERENCE 2 (residues 1 to 537) AUTHORS Boldt K, van Reeuwijk J, Lu Q, Koutroumpas K, Nguyen TM, Texier Y, van Beersum SE, ...
The spindle assembly checkpoint (SAC) prevents chromosome missegregation by coupling anaphase onset with correct chromosome attachment and tension to microtubules. It does this by generating a diffusible signal from free kinetochores into the cytoplasm, inhibiting the anaphase-promoting complex (APC). The volume in which this signal remains effective is unknown. This raises the possibility that cell volume may be the reason the SAC is weak, and chromosome segregation error-prone, in mammalian oocytes. Here, by a process of serial bisection, we analyzed the influence of oocyte volume on the ability of the SAC to inhibit bivalent segregation in meiosis I. We were able to generate oocytes with cytoplasmic volumes reduced by 86% and observed changes in APC activity consistent with increased SAC control. However, bivalent biorientation remained uncoupled from APC activity, leading to error-prone chromosome segregation. We conclude that volume is one factor contributing to SAC weakness in oocytes. ...
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 ...
As a result of checkpoint activation, a signalling cascade is initiated and a number of complexes between the checkpoint components are formed. This leads to the inhibition of the Anaphase Promoting Complex (APC), which is the ubiquitin ligase responsible for targeting mitotic proteins: securing and cyclin B for degradation by the 26S proteasome. The complexes formed include the MCC, or Mitotic Checkpoint Complex, which in fission yeast (Schizosaccharomyces pombe) consists of Mad2, Mad3 checkpoint proteins together with the APC activator, Slp1 (the Cdc20 homologue). The MCC has been shown to bind and inhibit the APC in HeLa cells. In my PhD I focused on the interactions between the MCC and the APC, in particular on Mad3 protein. Mad3 is a conserved checkpoint component, homologous to human BubR1. It carries 2 putative KEN boxes, motifs, which typically target proteins for degradation (like D-boxes). We mutated both KEN boxes in S. pombe Mad3 and show that they are essential for Mad3 checkpoint ...
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 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 ...
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 ...
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"MAD2 associates with the cyclosome/anaphase-promoting complex and inhibits its activity". Proc. Natl. Acad. Sci. U.S.A. 94 (23 ... Without Cdc20, the anaphase-promoting complex (APC) cannot become activated and anaphase is not triggered. Mad2 was shown to ... It is speculated that once formed, Cdc20:Mad2 complexes can amplify the anaphase wait signal by stimulating further conversion ... Given that Mad1:Mad2 is a stable complex and Cdc20 and Mad1 bind Mad 2 in the very same binding site, it is highly unlikely ...
The instability and drop in TPX2 at mitotic exit is dependent on both the anaphase-promoting complex/cyclosome (APC/C) and an ... Stewart S, Fang G (December 2005). "Anaphase-promoting complex/cyclosome controls the stability of TPX2 during mitotic exit". ... Stewart S, Fang G (December 2005). "Anaphase-promoting complex/cyclosome controls the stability of TPX2 during mitotic exit". ... Harper JW, Burton JL, Solomon MJ (September 2002). "The anaphase-promoting complex: it's not just for mitosis any more". Genes ...
This particular ligase is referred to as (APC/C) anaphase promoting complex or cyclosome. When the APC/C is inhibited, cyclin B ... The end result is each chromosome is attached to the spindle in the initial stage of anaphase. During normal mitosis, the SAC ...
"The DNA damage response mediator MDC1 directly interacts with the anaphase-promoting complex/cyclosome". J Biol Chem. 282 (44 ... This domain also binds to anaphase-promoting complex (APC/C) which is an E3 ubiquitin ligase that degrades cyclins. The BRCT ... de Jager M, van Noort J, van Gent DC, Dekker C, Kanaar R, Wyman C (Nov 2001). "Human Rad50/Mre11 is a flexible complex that can ... The MDC1s role in DDR is to function both as a mediator/adaptor protein mediating a complex of other DDR proteins at the site ...
... a regulator of the anaphase promoting complex/cyclosome". Proceedings of the National Academy of Sciences of the United States ... "Overexpression of the anaphase promoting complex/cyclosome inhibitor Emi1 leads to tetraploidy and genomic instability of p53- ... "Emi1 stably binds and inhibits the anaphase-promoting complex/cyclosome as a pseudosubstrate inhibitor". Genes & Development. ... Hansen DV, Loktev AV, Ban KH, Jackson PK (December 2004). "Plk1 regulates activation of the anaphase promoting complex by ...
Qiao D, Yang X, Meyer K, Friedl A (July 2008). "Glypican-1 regulates anaphase promoting complex/cyclosome substrates and cell ... In Drosophila, the glypican dally assists diffusion of the BMP-family growth-promoting morphogen Decapentaplegic in the ...
Zielke N; Querings S; Rottig C; Lehner C; Sprenger F (2008). "The anaphase-promoting complex/cyclosome (APC/C) is required for ... Cdh/fzr is responsible for activation of the anaphase-promoting complex (APC) and subsequent proteolysis of the mitotic cyclins ... The cytological picture in the tapetum is further complicated by restitution in anaphase and fusion of metaphase and anaphase ... Narbonne-Reveau K; Senger S; Pal M; Herr A; Richardson HE; Asano M; Deak P; Lilly MA (2008). "APC/CFzr/Cdh1 promotes cell cycle ...
"KEN-box-dependent degradation of the Bub1 spindle checkpoint kinase by the anaphase-promoting complex/cyclosome". The Journal ... Zhang Y, Lees E (Aug 2001). "Identification of an overlapping binding domain on Cdc20 for Mad2 and anaphase-promoting complex: ... Metaphase-to-anaphase transition is halted by the SAC as long as single kinetochores lack bipolar microtubule attachment, ... In turn APC/C, now in complex with Cdh1, also acts on Bub1 by priming it for degradation to exit mitosis. In addition, ...
A large protein complex, termed the anaphase-promoting complex (APC), or the cyclosome, promotes metaphase-anaphase transition ... 2004). "The Arabidopsis anaphase-promoting complex or cyclosome: molecular and genetic characterization of the APC2 subunit". ... Anaphase-promoting complex subunit 2 is an enzyme that in humans is encoded by the ANAPC2 gene. ... "Entrez Gene: ANAPC2 anaphase promoting complex subunit 2". Vodermaier, Hartmut C; Gieffers, Christian; Maurer-Stroh, Sebastian ...
There, he discovered the anaphase promoting complex/cyclosome (APC/C) and other enzymes required for chromosome segregation. In ... and was promoted to Senior Scientist in 2002. In 2011, he became the institute's Scientific Deputy Director and in 2013 ...
... forms a complex with BUB1 (BUB1/BUB3 complex) to inhibit the anaphase-promoting complex or cyclosome (APC/C) as soon as ... "Two different mitotic checkpoint inhibitors of the anaphase-promoting complex/cyclosome antagonize the action of the activator ... inhibit the action of the Anaphase Promoting Complex (APC), preventing early anaphase entry and mitotic exit; this serves as a ... "Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1". Molecular Cell. 2 ( ...
The END network couples spindle pole assembly to inhibition of the anaphase-promoting complex/cyclosome in early mitosis. ...
Cyclins are targeted for proteolytic degradation by the anaphase promoting complex (APC), also known as the cyclosome, a ... "Mitotic spindle disassembly occurs via distinct subprocesses driven by the anaphase-promoting complex, Aurora B kinase, and ... The anaphase-mediated distancing of chromosomes from the metaphase plate may trigger spatial cues for the onset of telophase. ... The nuclear pore complex is assembled and integrated in the nuclear envelope in an organized manner, consecutively adding ...
Zhao WM, Fang G (2005). "Anillin is a substrate of anaphase-promoting complex/cyclosome (APC/C) that controls spatial ... Zhao WM, Fang G (2005). "Anillin is a substrate of anaphase-promoting complex/cyclosome (APC/C) that controls spatial ... It has been observed that anillin proteolysis is triggered after mitotic exit by the Anaphase Promoting Complex (APC). Most ... Anillin may also be involved in promoting the polymerization of F-actin by stabilizing formin mDia2 in an active form. Anillin ...
... a meiosis-specific anaphase-promoting complex/cyclosome activator." PLOS Genetics 3 (11):e202. doi:10.1371/journal.pgen.0030202 ... They have shown that cortex protein specifically triggers the anaphase-promoting complex in ovaries and the degradation of ...
"The Apc5 subunit of the anaphase-promoting complex/cyclosome interacts with poly(A) binding protein and represses internal ... "Mammalian p55CDC mediates association of the spindle checkpoint protein Mad2 with the cyclosome/anaphase-promoting complex, and ... Kramer ER, Gieffers C, Hölzl G, Hengstschläger M, Peters JM (Nov 1998). "Activation of the human anaphase-promoting complex by ... Stroschein SL, Bonni S, Wrana JL, Luo K (Nov 2001). "Smad3 recruits the anaphase-promoting complex for ubiquitination and ...
"The Apc5 subunit of the anaphase-promoting complex/cyclosome interacts with poly(A) binding protein and represses internal ... The poly(A)-binding protein (PAB or PABP), which is found complexed to the 3' poly(A) tail of eukaryotic mRNA, is required for ... tail and a c-fos RNA coding determinant via a protein complex". Cell. 103 (1): 29-40. doi:10.1016/S0092-8674(00)00102-1. PMID ...
2004). "The Apc5 Subunit of the Anaphase-Promoting Complex/Cyclosome Interacts with Poly(A) Binding Protein and Represses ... 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 ... "Entrez Gene: ANAPC5 anaphase promoting complex subunit 5". Vodermaier, Hartmut C; Gieffers, Christian; Maurer-Stroh, Sebastian ...
... and the ANAPC2 subunit of the anaphase-promoting complex/cyclosome; both CUL9 and ANAPC2 have ubiquitin ligase activity. The N- ... part of the Anaphase-promoting complex. CUL1, 2, 3, 4A, 4B, 5 and 7 each form part of a multi-subunit ubiquitin complex. Cullin ... The human genome contains eight cullin genes CUL1, part of SCF complex CUL2, part of ECS complex (Elongin C - CUL2 - SOCS-box) ... CUL3, part of CUL3-BTB complex CUL4A CUL4B CUL5 CUL7 CUL9, also known as PARC There is also a more distant member called ANAPC2 ...
"Mammalian p55CDC mediates association of the spindle checkpoint protein Mad2 with the cyclosome/anaphase-promoting complex, and ... protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase ... protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase ... "Mammalian p55CDC mediates association of the spindle checkpoint protein Mad2 with the cyclosome/anaphase-promoting complex, and ...
"Mammalian p55CDC mediates association of the spindle checkpoint protein Mad2 with the cyclosome/anaphase-promoting complex, and ... "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 ... Stroschein SL, Bonni S, Wrana JL, Luo K (Nov 2001). "Smad3 recruits the anaphase-promoting complex for ubiquitination and ...
... protein has been localized to the kinetochore and plays a role in the inhibition of the anaphase-promoting complex/cyclosome ( ... Fang G (March 2002). "Checkpoint protein BubR1 acts synergistically with Mad2 to inhibit anaphase-promoting complex". Mol. Biol ... Sudakin V, Chan GK, Yen TJ (September 2001). "Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of ... "Human BUBR1 is a mitotic checkpoint kinase that monitors CENP-E functions at kinetochores and binds the cyclosome/APC". J. Cell ...
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 ... "Entrez Gene: ANAPC7 anaphase promoting complex subunit 7". CS1 maint: discouraged parameter (link) Vodermaier HC, Gieffers C, ... Park KH, Choi SE, Eom M, Kang Y (2006). "Downregulation of the anaphase-promoting complex (APC)7 in invasive ductal carcinomas ...
A large protein complex, termed the anaphase-promoting complex (APC), or the cyclosome, promotes metaphase-anaphase transition ... Anaphase-promoting complex subunit 4 is an enzyme that in humans is encoded by the ANAPC4 gene. ... "Entrez Gene: ANAPC4 anaphase promoting complex subunit 4". Vodermaier, Hartmut C; Gieffers, Christian; Maurer-Stroh, Sebastian ... 1999). "Characterization of the DOC1/APC10 subunit of the yeast and the human anaphase-promoting complex". J. Biol. Chem. 274 ( ...
... cadherin superfamily APC/C activator protein CDH1 Cell-cycle regulated activator of the anaphase-promoting complex/cyclosome ( ...
April 2015). "Structure of an APC3-APC16 complex: insights into assembly of the anaphase-promoting complex/cyclosome". Journal ... 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 ... Evidence shows that APC3 and APC7 serve to recruit Cdh1 to the anaphase promoting complex. This further supports that Cdh1 is ...
When anaphase onset is triggered, the anaphase-promoting complex (APC/C or Cyclosome) degrades securin. APC/C is a ring E3 ... After checkpoint deactivation and during the normal anaphase of the cell cycle, the anaphase promoting complex is activated ... Once activated, the spindle checkpoint blocks anaphase entry by inhibiting the anaphase-promoting complex via regulation of the ... The defining biochemical feature of this checkpoint is the stimulation of the anaphase-promoting complex by M-phase cyclin-CDK ...
MAD2 associates with the cyclosome/anaphase-promoting complex and inhibits its activity. Yong Li, Carlos Gorbea, David Mahaffey ... MAD2 associates with the cyclosome/anaphase-promoting complex and inhibits its activity ... MAD2 associates with the cyclosome/anaphase-promoting complex and inhibits its activity ... MAD2 associates with the cyclosome/anaphase-promoting complex and inhibits its activity ...
Geley, S., E. Kramer, C. Gieffers, J. Gannon, J. M. Peters et al., 2001 Anaphase-promoting complex/cyclosome-dependent ... Peters, J. M., 2006 The anaphase promoting complex/cyclosome: a machine designed to destroy. Nat. Rev. Mol. Cell Biol. 7: 644- ... Acquaviva, C., and J. Pines, 2006 The anaphase-promoting complex/cyclosome: APC/C. J. Cell Sci. 119: 2401-2404. ... Differential Regulation of Anaphase Promoting Complex/Cyclosome Substrates by the Spindle Assembly Checkpoint in Saccharomyces ...
The ubiquitin E3 ligase anaphase-promoting complex/cyclosome (APC/C) drives degradation of cell cycle regulators in cycling ... Anaphase-promoting complex/cyclosome Participates in the Acute Response to Protein-Damaging Stress Mol Cell Biol. 2010 Dec;30( ... The ubiquitin E3 ligase anaphase-promoting complex/cyclosome (APC/C) drives degradation of cell cycle regulators in cycling ... Anaphase-Promoting Complex-Cyclosome * Antigens, CD * Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome ...
cDNA FLJ55537, highly similar to Anaphase-promoting complex subunit 5 (APC5)(Cyclosome subunit 5)Imported. ,p>Information which ... tr,B4DFK4,B4DFK4_HUMAN cDNA FLJ55537, highly similar to Anaphase-promoting complex subunit 5 (APC5)(Cyclosome subunit 5) OS= ... cDNA FLJ55537, highly similar to Anaphase-promoting complex subunit 5 (APC5)(Cyclosome subunit 5). ... Anaphase-promoting complex subunit 5. ). HUMAN. 755. UniRef50_Q9UJX4. Anaphase-promoting complex subunit 5. PONAB ...
Model of human Anaphase-promoting complex/Cyclosome (APC/C-CDH1) with a cross linked Ubiquitin variant-substrate-UBE2C (UBCH10 ... Here, cryo-EM and biochemistry show that the human E3 anaphase-promoting complex/cyclosome (APC/C) and its two partner E2s, ... Anaphase-promoting complex subunit CDC26. G, W. 85. Homo sapiens. Mutation(s): 0 Gene Names: CDC26, ANAPC12, C9orf17. ... Anaphase-promoting complex subunit 16. E. 110. Homo sapiens. Mutation(s): 0 Gene Names: ANAPC16, C10orf104, CENP-27. ...
Polo-Like Kinase 1: Target and Regulator of Anaphase-Promoting Complex/Cyclosome-Dependent Proteolysis. Frank Eckerdt and Klaus ... Anaphase-Promoting Complex/Cyclosome Activity: Ordered Proteolysis of Mitotic Proteins, Including Polo-Like Kinase 1. A failure ... Uncoupling anaphase-promoting complex/cyclosome activity from spindle assembly checkpoint control by deregulating polo-like ... Anaphase-Promoting Complex/Cyclosome Activity: Ordered Proteolysis of Mitotic Proteins, Including Polo-Like Kinase 1 ...
anaphase-promoting complex/cyclosome. DAS. d after stratification. PAC. paclobutrazol. DEX. dexamethasone. ... 2011) GIGAS CELL1, a novel negative regulator of the anaphase-promoting complex/cyclosome, is required for proper mitotic ... Another major pathway is the control of anaphase-promoting complex/cyclosome (APC/C) activity through its activating CELL CYCLE ... ULTRAVIOLET-B-INSENSITIVE4 maintains cell division activity by temporal inhibition of the anaphase-promoting complex/cyclosome ...
2009). Structure of the anaphase-promoting complex/cyclosome interacting with a mitotic checkpoint complex. Science 323, 1477- ... One of the machineries that promotes protein destruction is the E3 ubiquitin ligase anaphase-promoting complex/cyclosome or APC ... 2006). The anaphase promoting complex/cyclosome: a machine designed to destroy. Nat. Rev. Mol. Cell. Biol. 7, 644-656. ... APC16 is a conserved subunit of the anaphase-promoting complex/cyclosome. Geert J. P. L. Kops, Monique van der Voet, Michael S ...
One of the key regulators of the SAC is the anaphase promoting complex/cyclosome (APC/C) which ubiquitinates cyclin B and ... Because APC/C not only ensures cell cycle arrest upon spindle disruption but also promotes cell death in response to prolonged ... is the major cell cycle control mechanism to delay the onset of anaphase during mitosis. ... Peters JM: The anaphase promoting complex/cyclosome: a machine designed to destroy. Nat Rev Mol Cell Biol. 2006, 7 (9): 644-656 ...
One of the key regulators of the SAC is the anaphase promoting complex/cyclosome (APC/C) which ubiquitinates cyclin B and ... Because APC/C not only ensures cell cycle arrest upon spindle disruption but also promotes cell death in response to prolonged ... is the major cell cycle control mechanism to delay the onset of anaphase during mitosis. ... Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis. Access & ...
The anaphase-promoting complex/cyclosome: a new promising target in diffuse large B-cell lymphoma and mantle cell lymphoma. ... The anaphase-promoting complex/cyclosome (APC/C) and its co-activators Cdc20 and Cdh1 represent an important checkpoint in ...
BIMAAPC3, a component of the Aspergillus anaphase promoting complex/cyclosome, is required for a G2 checkpoint blocking entry ... BIMAAPC3, a component of the Aspergillus anaphase promoting complex/cyclosome, is required for a G2 checkpoint blocking entry ... a component of the anaphase promoting complex/cyclosome (APC/C). Whereas nimA single mutants arrested in G2 with decondensed ... BIMAAPC3 was present in a ,25S complex containing BIMEAPC1, and bimAAPC3 mutants were sensitive to elevated CYCLIN B expression ...
A new function for the anaphase promoting complex/cyclosome. Together they form a unique fingerprint. * Anaphase-Promoting ... Zarnescu DC, Moses K. Born again at the synapse: A new function for the anaphase promoting complex/cyclosome. Developmental ... Zarnescu, D. C., & Moses, K. (2004). Born again at the synapse: A new function for the anaphase promoting complex/cyclosome. ... Born again at the synapse : A new function for the anaphase promoting complex/cyclosome. / Zarnescu, Daniela C.; Moses, Kevin. ...
Multiple anaphase-promoting complex/cyclosome degrons mediate the degradation of human sgo1. In: Journal of Biological ... Karamysheva, Z., Diaz-Martinez, L. A., Crow, S. E., Li, B., & Yu, H. (2009). Multiple anaphase-promoting complex/cyclosome ... Karamysheva Z, Diaz-Martinez LA, Crow SE, Li B, Yu H. Multiple anaphase-promoting complex/cyclosome degrons mediate the ... Multiple anaphase-promoting complex/cyclosome degrons mediate the degradation of human sgo1. / Karamysheva, Zemfira; Diaz- ...
The anaphase-promoting complex/cyclosome in control of plant development. Oct 5, 2012·Molecular Plant·Jefri Heyman, Lieven De ... The anaphase-promoting complex/cyclosome (APC/C) is a multisubunit ubiquitin ligase that regulates progression through the cell ... The Arabidopsis anaphase-promoting complex/cyclosome subunit 1 is critical for both female gametogenesis and embryogenesis(F). ... The anaphase-promoting complex/cyclosome in control of plant development. (opens in new tab) ...
ANAPC4; Anaphase-promoting complex, cyclosome, subunit 4. * NM_013367.3 → NP_037499.2 anaphase-promoting complex subunit 4 ... ANAPC4; Anaphase-promoting complex, cyclosome, subunit 4. * XM_017008138.2 → XP_016863627.1 anaphase-promoting complex subunit ... ANAPC4; Anaphase-promoting complex, cyclosome, subunit 4. * XM_011513838.1 → XP_011512140.1 anaphase-promoting complex subunit ... ANAPC4; Anaphase-promoting complex, cyclosome, subunit 4. * XM_005248159.2 → XP_005248216.1 anaphase-promoting complex subunit ...
Transcriptional intermediary factor 1γ binds to the anaphase-promoting complex/cyclosome and promotes mitosis. * ... The anaphase-promoting complex/cyclosome (APC/C) is an ubiquitin ligase that functions during mitosis. Here we identify the ... Binding studies indicate that TIF1γ is also a component of the APC/C-mitotic checkpoint complex (MCC), but is not required for ... and an increase in the time taken for cells to progress through mitosis from nuclear envelope breakdown to anaphase. TIF1γ ...
Orthologues of the Anaphase-Promoting Complex/Cyclosome Coactivators Cdc20p and Cdh1p Are Important for Mitotic Progression and ... Early mitotic inhibitor 1 (Emi1) inhibits the activity of the anaphase promoting complex/cyclosome (APC/C), which is a ... Regulation of the Action of Early Mitotic Inhibitor 1 on the Anaphase-promoting Complex/Cyclosome by Cyclin-dependent Kinases ... Abbreviations: Emi1, early mitotic inhibitor 1; APC/C, anaphase promoting complex/cyclosome; Plk, Polo-like kinase; SCF, Skp1- ...
Ubiquitin-Protein Ligase Complexes * Anaphase-Promoting Complex-Cyclosome * Ubiquitin-Protein Ligases * Ligases ...
... in particular the metaphase to anaphase transition in mitosis and the reentry into G1 phase. Inhibition of the APC/C results in ... The anaphase promoting complex/cyclosome (APC/C) is a large, E3 ubiquitin ligase that regulates the cell cycle, ... The anaphase promoting complex/cyclosome (APC/C) is a large, E3 ubiquitin ligase that regulates the cell cycle, in particular ... The anaphase promoting complex/cyclosome (APC/C) is a large, E3 ubiquitin ligase that regulates the cell cycle, in particular ...
APC- anaphase-promoting complex/cyclosome SCF- Skp1-Cdc53/Cu11-F-box protein ... The complex then binds the particular protein and the E2-Ub complex, facilitating the transfer of Ub to tag the protein. ... The enzyme binds an ATP-activated Ub complex where a transfer of the Ub to the a cysteine residue on E1 forms the thioester ... Ub is then transferred to a Ub-conjugating protein (E2) and finally that protein complex is recognized by a Ub-protein ligase ( ...
The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the ... Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls ... Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls ... Anaphase-promoting complex subunit 4Add BLAST. 807. Amino acid modifications. Feature key. Position(s). DescriptionActions. ...
IPR024990 Anaphase-promoting complex subunit 1. IPR002015 Proteasome/cyclosome repeat. Molecular. Reagents ...
anaphase-promoting complex/cyclosome. NUSAP. nucleolar and spindle-associated protein. SILAC. stable isotope labeling by amino ... which activates the anaphase-promoting complex/cyclosome (APC/C).1 The net effect is to mimic most or all of the known ... and anaphase-promoting complex/cyclosome. Our approach can be extended to other cellular compartments and cell states, and our ... 2000) Degradation of human Aurora2 protein kinase by the anaphase-promoting complex-ubiquitin-proteasome pathway. Oncogene 19, ...
anaphase-promoting complex/cyclosome. APC/C. inducible Rictor-knockout. iRiKO. mouse embryonic fibroblasts. MEFs. tryptic soy ... an anaphase-promoting complex/cyclosome (APC/C) inhibitor (54). The addition of Mad2L2 to the STRING network representation of ... nuclear pore complex. NPC. mTOR complex 1. mTORC1. mTOR complex 2. mTORC2. regulatory-associated protein of mTOR. Raptor. ... 1999) Activation of the Cdc42 effector N-Wasp by the Shigella flexneri Icsa protein promotes actin nucleation by Arp2/3 complex ...
Apc1 is the largest of the subunits of the anaphase-promoting complex or cyclosome. The anaphase-promoting complex is a ... The anaphase promoting complex/cyclosome: a machine designed to destroy.. Nat. Rev. Mol. Cell Biol. 7 644-56 2006 ... Characterisation of the human APC1, the largest subunit of the anaphase-promoting complex.. Gene 262 51-9 2001 ... Accumulation of substrates of the anaphase-promoting complex (APC) during human cytomegalovirus infection is associated with ...
Anaphase Promoting Complex/ Cyclosome; MPF, M-phase Promoting Factor; CSF, Cytostatic Factor; GVBD, Germinal Vesicle Breakdown ... delays the metaphase-to-anaphase transition by inhibiting the anaphase promoting complex/cyclosome (APC/C) coupled to its ... or is equally promoting anaphase onset in mitosis. As BubR1s role for promoting progression through anaphase I is not ... Lane, S. I., Yun, Y., and Jones, K. T. (2012). Timing of anaphase-promoting complex activation in mouse oocytes is predicted by ...
The anaphase promoting complex/cyclosome: a machine designed to destroy. Nat. Rev. Mol. Cell Biol. 7:644-656. doi:10.1038/ ... anaphase-promoting complex/cyclosome. DPI. diphenyleneiodonium. MAFP. methyl arachidonyl fluorophosphonate. MEF. mouse ... Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1. Mol. Cell. 2:163-171 ... to prevent premature dephosphorylation of Cdh1-an activator of the ubiquitin ligase anaphase-promoting complex/cyclosome-and ...
Peters, J.-M. The anaphase promoting complex/cyclosome: a machine designed to destroy. Nat. Rev. Mol. Cell Biol. 7, 644-656 ( ... SOCS3 binds specific receptor-JAK complexes to control cytokine signaling by direct kinase inhibition. Nat. Struct. Mol. Biol. ... Cardote, T. A. F., Gadd, M. S. & Ciulli, A. Crystal structure of the Cul2-Rbx1-EloBC-VHL ubiquitin ligase complex. Structure 25 ... The EED protein-protein interaction inhibitor A-395 inactivates the PRC2 complex. Nat. Chem. Biol. 13, 389-395 (2017). ...
... such as the anaphase promoting complex/cyclosome (APC/C), the SKP1-cullin 1-F-box protein (SCF) E3s, MDM2, BRCA1, Fanconi ... and anaphase-promoting complex/cyclosome (APC/C) multisubunit RING finger E3s. These complexes are targeted to specific ... Peters, J. M. The anaphase promoting complex/cyclosome: a machine designed to destroy. Nature Rev. Mol. Cell Biol. 7, 644-656 ( ... such as the anaphase promoting complex/cyclosome (APC/C), the SKP1-cullin 1-F-box protein (SCF) E3s, MDM2, BRCA1, Fanconi ...
  • APC/C function is critical for progression through mitosis where it degrades Pds1 (securin in higher eukaryotic cells) and other substrates to promote anaphase and the exit from mitosis ( P ines 2006 ). (genetics.org)
  • Recent evidence suggests that a major role of Plk1 in exit from mitosis is the regulation of inhibitors of the anaphase-promoting complex/cyclosome (APC/C), such as the early mitotic inhibitor 1 (Emi1) and spindle checkpoint proteins. (aacrjournals.org)
  • Mitotic exit and onset of endoreduplication do not correlate with an up-regulation of known cell cycle inhibitors but are the result of reduced levels of DP-E2F-LIKE1/E2Fe and UV-B-INSENSITIVE4, both inhibitors of the developmental transition from mitosis to endoreduplication by modulating anaphase-promoting complex/cyclosome activity, which are down-regulated rapidly after DELLA stabilization. (plantphysiol.org)
  • The mitotic checkpoint, or spindle assembly checkpoint (SAC), is the major cell cycle control mechanism to delay the onset of anaphase during mitosis. (biomedcentral.com)
  • The anaphase-promoting complex/cyclosome (APC/C) and its co-activators Cdc20 and Cdh1 represent an important checkpoint in mitosis. (vub.be)
  • BIMAAPC3, a component of the Aspergillus anaphase promoting complex/cyclosome, is required for a G2 checkpoint blocking entry into mitosis in the absence of NIMA function. (uky.edu)
  • it peaks in mitosis and is down-regulated in G 1 /S. Here we show that Sgo1 is degraded during the exit from mitosis, and its degradation depends on the anaphase-promoting complex/cyclosome (APC/C). Overexpression of Cdh1 reduces the protein levels of ectopically expressed Sgo1 in human cells. (elsevier.com)
  • Early mitotic inhibitor 1 (Emi1) inhibits the activity of the anaphase promoting complex/cyclosome (APC/C), which is a multisubunit ubiquitin ligase that targets mitotic regulators for degradation in exit from mitosis. (pnas.org)
  • Previous studies have shown that Emi1 is targeted for degradation in mitosis by a Skp1-Cullin1 F-box protein (SCF) ubiquitin ligase complex that contains the F-box protein β-TrCP. (pnas.org)
  • A good example for the interrelationship between these two processes is the intricate regulation of the anaphase promoting complex/cyclosome (APC/C). APC/Cisa large, multisubunit ubiquitin ligase complex ( 1 , 2 ) that targets mitotic regulators for degradation in exit from mitosis (reviewed in refs. (pnas.org)
  • The anaphase-promoting complex/cyclosome (APC/C) is an ubiquitin ligase that functions during mitosis. (forskningsdatabasen.dk)
  • 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. (forskningsdatabasen.dk)
  • Together these data define novel functions for TIF1γ during mitosis and suggest that a reduction in APC/C ubiquitin ligase activity promotes SAC activation. (forskningsdatabasen.dk)
  • 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. (uniprot.org)
  • The anaphase promoting complex/cyclosome (APC/C) is a large, E3 ubiquitin ligase that regulates the cell cycle, in particular the metaphase to anaphase transition in mitosis and the reentry into G1 phase. (murraystate.edu)
  • The anaphase-promoting complex is a multiprotein subunit E3 ubiquitin ligase complex that controls segregation of chromosomes and exit from mitosis in eukaryotes [ PMID: 11179667 , PMID: 16896351 ]. (ebi.ac.uk)
  • The activity of Cdk1-opposing phosphatases at the centrosome must be inhibited during early mitosis to prevent premature dephosphorylation of Cdh1-an activator of the ubiquitin ligase anaphase-promoting complex/cyclosome-and the consequent premature degradation of mitotic activators. (rupress.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)
  • Progression through mitosis relies on a complex series of precisely coordinated events that is primarily regulated by the periodic rise and fall of mitotic B-type cyclin levels. (aacrjournals.org)
  • See " Sustained Mps1 activity is required in mitosis to recruit O-Mad2 to the Mad1-C-Mad2 core complex " in volume 190 on page 25. (pubmedcentralcanada.ca)
  • Mps1 inhibition sharply accelerated anaphase onset, such that cells completed mitosis in 12 min, and prevented Cdc20's association with either Mad2 or BubR1 during interphase, i.e., before the appearance of functional kinetochores. (pubmedcentralcanada.ca)
  • 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) is a multicomponent E3 ubiquitin ligase that, by targeting protein substrates for 26S proteasome-mediated degradation through ubiquitylation, coordinates the temporal progression of eukaryotic cells through mitosis and the subsequent G1 phase of the cell cycle. (birmingham.ac.uk)
  • The APC/C (anaphase-promoting complex/cyclosome) targets a large number of substrates for proteolysis during the final steps of mitosis and cytokinesis, but the significance of these targeting events, particularly in mammalian cells, is largely unknown. (portlandpress.com)
  • The spindle checkpoint monitors the interaction between spindle microtubules and kinetochores to prevent precocious entry into anaphase, delaying this stage of mitosis until all condensed chromosomes have been attached to the mitotic spindle in a bi-oriented manner (so that the two kinetochores associated with a pair of sister chromatids are oriented toward opposite poles of the spindle). (sciencemag.org)
  • During interphase, MAD1L1 regulates mitosis entrance at nuclear pore complexes (MAD2L1-dependent mechanism) and Golgi apparatus-related functions (MAD2L1-independent mechanism). (atlasgeneticsoncology.org)
  • Upper panel) During mitosis, MAD1L1 binds to improperly attached kinetochrore, what results in recruitment and interaction with MAD2L1, and activation of the mitotic checkpoint complex (MCC). (atlasgeneticsoncology.org)
  • Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1. (proteopedia.org)
  • Characterisation of the human APC1, the largest subunit of the anaphase-promoting complex. (ebi.ac.uk)
  • 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. (creativebiomart.net)
  • TITLE Identification of a cullin homology region in a subunit of the anaphase-promoting complex JOURNAL Science 279 (5354), 1219-1222 (1998) PUBMED 9469815 COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. (genome.jp)
  • TITLE Characterization of the DOC1/APC10 subunit of the yeast and the human anaphase-promoting complex JOURNAL J. Biol. (genome.jp)
  • Activation of the human anaphase-promoting complex by proteins of the CDC20/Fizzy family. (proteopedia.org)
  • The cyclosome/APC is composed of at least eight subunits including the BIME, CDC16, CDC23 , and CDC27 gene products, which are required for the metaphase-anaphase transition ( 4 , 9 , 11 , 12 , 14 - 16 ), providing further evidence that the cyclosome is involved in the degradation of the inhibitor(s) of this transition as well as cyclin B ( 17 ). (pnas.org)
  • The anaphase promoting complex (APC) targets proteins for degradation to promote progression through the cell cycle. (genetics.org)
  • The ubiquitin E3 ligase anaphase-promoting complex/cyclosome (APC/C) drives degradation of cell cycle regulators in cycling cells by associating with the coactivators Cdc20 and Cdh1. (nih.gov)
  • Moreover, degradation of hyperactive Plk1 T210D is impaired, suggesting that Plk1 inactivation during anaphase may be required for its timely degradation. (aacrjournals.org)
  • Inactivation and disassembly of the anaphase-promoting complex during human cytomegalovirus infection is associated with degradation of the APC5 and APC4 subunits and does not require UL97-mediated phosphorylation of Cdh1. (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 (By similarity). (uniprot.org)
  • Fig. 2: Structures of ternary complexes formed during targeted protein degradation. (nature.com)
  • Protacs: chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation. (nature.com)
  • Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4CRBN. (nature.com)
  • The VHL complex targets the hypoxia-inducible factor-α (HIFα) transcription factors for proteasomal degradation, which prevents the expression of angiogenic and growth-promoting genes under normoxic conditions. (nature.com)
  • 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. (genecards.org)
  • Literature reveals that there there exists a stringent balance between the de novo synthesis and targeted degradation of cyclins by the phosphorylation of specific residues, which prompt their recruitment and incorporation into multiprotein destruction complexes (Skp 1-Cullin-F-box protein (SCF) or anaphasepromoting complex/cyclosome (APC/C) and subsequent degradation within the proteasome [ 3 ]. (omicsonline.org)
  • The DCX(DTL) complex, also named CRL4(CDT2) complex, mediates the polyubiquitination and subsequent degradation of CDT1 and CDKN1A/p21(CIP1). (abcam.com)
  • Most substrates require their interaction with PCNA for their polyubiquitination: substrates interact with PCNA via their PIP-box, and those containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to their degradation. (abcam.com)
  • 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)
  • Degradation of specific protein substrates by the anaphase-promoting complex/cyclosome (APC) is critical for mitotic exit. (duke.edu)
  • Active APC/C also promotes the degradation of another substrate securin. (elifesciences.org)
  • 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)
  • 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)
  • ANAPC13 encodes a component of the anaphase promoting complex, a large ubiquitin-protein ligase that controls cell cycle progression by regulating the degradation of cell cycle regulators such as B-type cyclins. (antikoerper-online.de)
  • Once activated, this checkpoint arrests cells prior to the metaphase-anaphase transition with unsegregated chromosomes, stable cyclin B, and elevated M phase promoting factor activity. (pnas.org)
  • Thus, MAD2 links the mitotic checkpoint pathway to the cyclin B destruction machinery which is critical in controlling the metaphase-anaphase transition. (pnas.org)
  • The metaphase-anaphase transition is monitored by the mitotic checkpoint, which senses spindle aberrations and responds by arresting the cell cycle, thereby preventing aberrant chromosome segregation ( 18 - 20 ). (pnas.org)
  • Once activated, the mitotic checkpoint arrests the cell cycle prior to the metaphase-anaphase transition with unsegregated chromosomes and high levels of cyclin B, suggesting that the cyclosome might be the target of the response pathway. (pnas.org)
  • Detailed research revealed that the involvement of Plk1 is crucial for the metaphase-anaphase transition. (aacrjournals.org)
  • 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. (nih.gov)
  • Thus, Plk1 and the APC/C control mitotic regulators by both phosphorylation and targeted ubiquitylation to ensure the fidelity of chromosome separation at the metaphase to anaphase transition. (aacrjournals.org)
  • 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. (forskningsdatabasen.dk)
  • The spindle checkpoint system is a regulatory system that restrains progression through the metaphase-to-anaphase transition. (wikipedia.org)
  • The protein was shown to be present at unattached kinetochores and antibody inhibition studies demonstrated it was essential to execute a block in the metaphase-to-anaphase transition in response to the microtubule poison nocodazole. (wikipedia.org)
  • The cell cycle surveillance mechanism that prevents sister-chromatid separation and transition into anaphase is called the spindle checkpoint. (wikipedia.org)
  • This diffusible signal propagation away from the kinetochore complexes could account for how vacancy of just one tiny kinetochore site can completely shut down the metaphase-to-anaphase transition. (wikipedia.org)
  • Eukaryotic cells have solved this 'anaphase problem' by disabling the mitotic checkpoint at the metaphase-to-anaphase transition. (biochemsoctrans.org)
  • Only in the controlled case, our models show (M)SAC behaviour at meta- to anaphase transition in agreement with experimental observations. (nih.gov)
  • Here we report that upon activation of the mitotic checkpoint, MAD2, an essential component of the mitotic checkpoint, associates with the cyclin B-ubiquitin ligase, known as the cyclosome or anaphase-promoting complex. (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)
  • The Mitotic Checkpoint Complex Requires an Evolutionary Conserved Cassette to Bind and Inhibit Active APC/C. Di Fiore B, et al . (nih.gov)
  • The mitotic checkpoint complex binds a second CDC20 to inhibit active APC/C. Izawa D, et al . (nih.gov)
  • Binding studies indicate that TIF1γ is also a component of the APC/C-mitotic checkpoint complex (MCC), but is not required for MCC dissociation from the APC/C once the spindle assembly checkpoint (SAC) is satisfied. (forskningsdatabasen.dk)
  • Recruitment of Mad1-Mad2 complexes to unattached kinetochores is a central event in spindle checkpoint signaling. (rupress.org)
  • These results delineate an interaction between BUB-1 and MAD-1 that targets MAD-1-MAD-2 complexes to kinetochores and is essential for spindle checkpoint signaling. (rupress.org)
  • A, left) Schematic of checkpoint signaling mediated by kinetochore-anchored Mad1-Mad2 complexes. (rupress.org)
  • The activity of APC is highly regulated by checkpoint mechanisms that prevent APC activation and entry into anaphase ( 15 , 16 ). (aacrjournals.org)
  • As a safeguard against chromosome segregation errors, the spindle assembly checkpoint (SAC) delays anaphase until all sister chromatid pairs have become bipolarly attached. (wikipedia.org)
  • When the checkpoint/braking process is activated, Mad2 binds Mad1 to form Closed-Mad2-Mad1 complexes. (wikipedia.org)
  • It is also quite unclear how p31comet antagonizes the checkpoint and promotes the dissociation of Mad2-Cdc20. (wikipedia.org)
  • The spindle assembly checkpoint ( SAC ) is such a mechanism that delays anaphase onset when any kinetochore is not properly attached to the spindle fibers or when sister kinetochores are not under tension ( Musacchio and Salmon, 2007 ). (plantcell.org)
  • The spindle assembly checkpoint (SAC) in mammals uses cytosolic and kinetochore-based signaling pathways to inhibit anaphase. (pubmedcentralcanada.ca)
  • Paramount among these is the so-called spindle assembly checkpoint (SAC), which inhibits anaphase onset until all kinetochore pairs have attached to microtubules (MTs) emanating from both spindle poles, generating a stable configuration termed chromosome biorientation (for review see Musacchio and Salmon, 2007 ). (pubmedcentralcanada.ca)
  • The mitotic checkpoint monitors the attachment of kinetochores to microtubules and delays anaphase onset until all sister kinetochores have become attached to opposite poles. (biochemsoctrans.org)
  • In this review we focus on a poorly understood but important aspect of mitotic control: what prevents the mitotic checkpoint from springing into action when sister centromeres are split and tension is suddenly lost at anaphase onset? (biochemsoctrans.org)
  • Mitotic checkpoint inactivation at anaphase onset is required to prevent checkpoint re-engagement when sister chromatids split. (biochemsoctrans.org)
  • hZw10, along with its partners Rod (Roughdeal) and hZwilch, form a complex which recruits dynein-dynactin and Mad1-Mad2 complexes to the kinetochore and are essential components of the mitotic checkpoint. (biochemj.org)
  • This checkpoint guarantees that anaphase onset is initiated only when all chromosomes are properly attached to microtubules and aligned at the metaphase plate. (biologists.org)
  • The Mitotic Spindle Assembly Checkpoint ((M)SAC) is an evolutionary conserved mechanism that ensures the correct segregation of chromosomes by restraining cell cycle progression from entering anaphase until all chromosomes have made proper bipolar attachments to the mitotic spindle. (nih.gov)
  • TITLE Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2 JOURNAL J. Cell Biol. (genome.jp)
  • TITLE Human BUBR1 is a mitotic checkpoint kinase that monitors CENP-E functions at kinetochores and binds the cyclosome/APC JOURNAL J. Cell Biol. (genome.jp)
  • Biochemically, activated spindle checkpoint components have been shown to suppress the activity of the anaphase promoting complex/cyclosome. (sciencemag.org)
  • MAD1L1 is coiled-coil protein that binds to improperly attached kinetochrore, what results in recruitment and interaction with MAD2L1, activation of the mitotic checkpoint complex, inhibition of the anaphase-promoting complex/cyclosome and cell cycle arrest. (atlasgeneticsoncology.org)
  • One of the core components of this checkpoint is BubR1, a modular protein that acts to inhibit the activity of the large multi-protein E3 ubiquitin ligase known as the anaphase promoting complex/cyclosome (APC/C), by binding to the co-activating subunit Cdc20 [9] . (prolekare.cz)
  • The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation. (proteopedia.org)
  • Microtubule binding by the Spindle and Kinetochore Associated (Ska) complex concentrates protein phosphatase 1 at metaphase kinetochores to overcome the spindle checkpoint thus driving anaphase onset and mitotic exit. (elifesciences.org)
  • associating first with centrosomes in prophase, with kinetochores in prometaphase and metaphase, at the central spindle in anaphase, and in the midbody during telophase [ PMID: 17172872 , PMID: 16849530 , PMID: 15838519 ]. (ebi.ac.uk)
  • We conclude that Mps1 has two complementary roles in SAC regulation: (1) initial cytoplasmic activation of Cdc20 inhibitors and (2) recruitment of factors that promote sustained anaphase inhibition and chromosome biorientation to unattached kinetochores. (pubmedcentralcanada.ca)
  • Lower panel) In absence of unattached kinetochores, MAD1L1/MAD2L1 complex is not recruited, what results in chromosome segregation during anaphase. (atlasgeneticsoncology.org)
  • The SAC prevents the onset of anaphase by stabilizing Pds1 by inhibiting APC Cdc20 activity, allowing time for establishment of proper attachment, orientation, and alignment of chromosomes ( L ew and B urke 2003 ). (genetics.org)
  • As the condensed chromosomes attach to spindle microtubules and become properly aligned at the metaphase plate, a large multisubunit ubiquitin ligase known as the anaphase-promoting complex (APC) becomes activated and degrades cyclin B ( 5 , 6 ). (aacrjournals.org)
  • Considerable evidence suggests that diffusible Ran-GTP near mitotic chromatin facilitates the release of critical factors from nuclear transport receptors, thereby promoting organization of mitotic spindles with respect to chromosomes. (biochemsoctrans.org)
  • Separation of the sister chromatids during anaphase II pulls a haploid set of chromosomes into each of four lobes of the nucleus. (asm.org)
  • MAD1L1 belongs to the assembly control of the mitotic spindle, which acts as a component capable of blocking the onset of the anaphase if the chromosomes are not correctly aligned on the metaphase plate (Hardwick and Murray, 1995). (atlasgeneticsoncology.org)
  • 25S complex containing BIMEAPC1, and bimAAPC3 mutants were sensitive to elevated CYCLIN B expression, consistent with BIMAAPC3 being a component of the APC/C. Inactivation of bimAAPC3 had little affect on the steady state levels of the B-type cyclin, NIMECyclin B. Our results indicate that BIMAAPC3, and most likely the APC/C itself, is activated in G2 in nimA mutants. (uky.edu)
  • Infection of human fibroblasts with human cytomegalovirus (HCMV) leads to cell cycle dysregulation, which is associated with the inactivation of the anaphase-promoting complex [ PMID: 17942546 ]. (ebi.ac.uk)
  • This method works in part by global inhibition of CDK1, in part by activation of phosphatases ( 5 ), and in part by activating Cdh1 (through loss of inhibitory CDK1 phosphorylation ( 10 )), which activates the anaphase-promoting complex/cyclosome (APC/C). 1 The net effect is to mimic most or all of the known regulation that occurs after normal anaphase onset. (mcponline.org)
  • Accumulation of substrates of the anaphase-promoting complex (APC) during human cytomegalovirus infection is associated with the phosphorylation of Cdh1 and the dissociation and relocalization of APC subunits. (ebi.ac.uk)
  • The brk1 mutants are sterile due to the precocious separation of sister chromatids at the onset of anaphase I. The centromeric recruitment of SHUGOSHIN1 and phosphorylation of histone H2A at Thr-134 (H2A-pT134) depend on BRK1. (plantcell.org)
  • Although levels of Cdks remain constant throughout the cell cycle, their activities oscillate, mostly owing to complex cell cycle-dependent phosphorylation events and changes in the abundance of Cyclins [ 5 ]. (royalsocietypublishing.org)
  • Strikingly, nuclear staining revealed a close association of BRAF35/BRCA2 complex with condensed chromatin coincident with histone H3 phosphorylation. (embl-heidelberg.de)
  • Moreover, purified MAD2 causes a metaphase arrest in cycling Xenopus laevis egg extracts and prevents cyclin B proteolysis by blocking its ubiquitination, indicating that MAD2 functions as an inhibitor of the cyclosome. (pnas.org)
  • Vertebrate eggs are arrested at Metaphase II by Emi2, the meiotic anaphase-promoting complex/cyclosome (APC/C) inhibitor. (duke.edu)
  • The Anaphase-Promoting Complex Inhibitor, TAME, also referenced under CAS 1784-03-8, controls the biological activity of Anaphase-Promoting Complex. (merckmillipore.com)
  • TAME is a potent ubiquitin ligase inhibitor that specifically blocks Anaphase-Promoting Complex (APC) activation by directly binding to APC and disrupts the IR-tail-dependent interactions between APC and its activator proteins Cdc20 or Cdh1. (merckmillipore.com)
  • The central regulator, cyclin B-Cdk1 complex activates its own activator, phosphatase Cdc25, forming a positive feedback loop, and inhibits its own inhibitor, kinase Wee1, forming a double negative feedback loop. (elifesciences.org)
  • Luo and Yu, 2008 ) that promotes its association with the APC/C activator Cdc20 to restrict APC/C activity until microtubule attachment removes Mad1-Mad2 from the kinetochore. (rupress.org)
  • hZwint-1 localizes to the kinetochore in prophase, before hZw10 localization, and remains at the kinetochore until anaphase, after hZw10 has dissociated. (biochemj.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)
  • These complexes are targeted to specific substrates via interchangeable substrate recognition subunits, including F-box proteins for SCF and cell division cycle 20 (CDC20) and CDH1 for APC/C. These multisubunit E3s have a large number of substrates with oncogenic and tumour suppressive effects. (nature.com)
  • Is regulated by MAD2L1: in metaphase the MAD2L1-CDC20-APC/C ternary complex is inactive and in anaphase the CDC20-APC/C binary complex is active in degrading substrates. (proteopedia.org)
  • Progression from metaphase to anaphase is marked by sister chromatid separation. (wikipedia.org)
  • Destruction of the inhibitory protein securin releases active separase, which triggers sister chromatid separation and anaphase onset by cleaving cohesin. (plantcell.org)
  • The anaphase promoting complex/cyclosome (APC/C) is the E3 subunit of an ubiquitin-conjugating enzyme composed of at least thirteen subunits that targets proteins for proteolysis during the cell cycle ( P eters 2006 ). (genetics.org)
  • The APC/C Cdh1 complex targets not only D box-containing proteins but also proteins exhibiting a KEN box and/or an A box (e.g., cyclin B1 and Aurora A). Plk1 itself is an APC/C Cdh1 target. (aacrjournals.org)
  • The anaphase-promoting complex/cyclosome (APC/C) is a multisubunit ubiquitin ligase that regulates progression through the cell cycle by marking key cell division proteins for destruction. (meta.org)
  • During infection, several injected effector proteins promote bacterial internalization, and interfere with multiple host cell responses. (mcponline.org)
  • Upon contact between the tip complex of the type III apparatus and host cell receptors, including α5β1-integrins and CD44, the secreted proteins IpaB and IpaC insert into the plasma membrane and form a pore into the host membrane through which several effectors translocate ( 10 ⇓ ⇓ ⇓ - 14 ). (mcponline.org)
  • The myeloma drug lenalidomide promotes the cereblon-dependent destruction of ikaros proteins. (nature.com)
  • Many RING finger E3s have roles in processes that are central to the maintenance of genomic integrity and cellular homeostasis, such as the anaphase promoting complex/cyclosome (APC/C), the SKP1-cullin 1-F-box protein (SCF) E3s, MDM2, BRCA1, Fanconi anaemia proteins, CBL proteins, von Hippel-Lindau tumour suppressor (VHL) and SIAH proteins. (nature.com)
  • BubR1 and Bub3 can also form complexes with Cdc20, but it remains to be seen if these proteins facilitate Cdc20 binding to Open Mad2. (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)
  • A major determinant of complexity is the reversible post-translational modification (PTM) of proteins, which generates variants displaying distinct biological properties such as subcellular localization, enzymatic activity and the ability to assemble in complexes. (frontiersin.org)
  • We have constructed and validated for the human (M)SAC mechanism an in silico dynamical model, integrating 11 proteins and complexes. (nih.gov)
  • Originating from the biochemical reactions for the underlying molecular processes, non-linear ordinary differential equations for the concentrations of 11 proteins and complexes of the (M)SAC are derived. (nih.gov)
  • We anticipate that this approach will help identify proteins that function in DNA damage response pathways or anti-viral/stress response pathways and that are targeted by adenovirus in order to facilitate viral replication and/or promote adenovirus-mediated cellular transformation. (birmingham.ac.uk)
  • FBPs are structurally and functionally diverse, and their activity is crucial for selecting proteins that will be targeted by the SCF complex. (mdpi.com)
  • One of the key regulators of the SAC is the anaphase promoting complex/cyclosome (APC/C) which ubiquitinates cyclin B and securin and targets them for proteolysis. (biomedcentral.com)
  • The anaphase-promoting complex/cyclosome (APC/C) promotes anaphase onset and mitotic exit through ubiquitinating securin and cyclin B1. (proteopedia.org)
  • Apc1 is the largest of the subunits of the anaphase-promoting complex or cyclosome. (ebi.ac.uk)
  • This is made possible partially by TPX2's role in sequestering free tubulin subunits and nucleating small multi-subunit tubulin complexes, which inadvertently also slows the rate of growth by decreasing the effective free tubulin concentration. (wikipedia.org)
  • Plk1 is exclusively expressed in proliferating cells regulating a diverse set of processes, including centrosome maturation, bipolar spindle formation, activation of the cyclin B/cyclin-dependent kinase 1 (Cdk1) complex, and cytokinesis. (aacrjournals.org)
  • We showed that mTOR complex 1 and 2 were required for S6 kinase and AKT activation, respectively. (mcponline.org)
  • The cell cycle is regulated by the S phase kinase-associated protein 1 (SKP1)-cullin 1 (CUL1)-F-box protein (SCF) and anaphase-promoting complex/cyclosome (APC/C) multisubunit RING finger E3s. (nature.com)
  • Aurora B kinase, the catalytic subunit of the CPC (chromosomal passenger complex), acts as a sensor and effector in both pathways. (biochemsoctrans.org)
  • Her præsenterer vi en protokol for en in vitro- kinase assay med Cdk1, som giver mulighed for identifikation af Cdk1-specifikke fosforylering websteder til oprettelse af cellulære mål for denne vigtige kinase. (jove.com)
  • Her, beskriver vi en in vitro- kinase assay, der bruges til at identificere Cdk1-specifikke fosforylering websteder. (jove.com)
  • Vi beskriver også rensning protokoller, der giver meget rene og homogen protein præparater egnet til kinase assay, og et bindende assay funktionelle verifikation af de identificerede fosforylering websteder, som sonder samspillet mellem en klassisk nukleare lokalisering signal (cNLS) og dens nukleare transport receptor karyopherin α. (jove.com)
  • Progression through this cycle involves a large number of dedicated protein complexes and signaling pathways, and deregulation of this process is implicated in tumorigenesis. (sciencemag.org)
  • Progression of cells through four sequential phases of cell cycle namely, G 1 , S, G 2 and M phase is tightly controlled and monitored by checkpoints, the enzymatic complexes known as CDKs. (omicsonline.org)
  • PI3K/AKT/mTOR Pathway Alterations Promote Malignant Progression and Xenograft Formation in Oligodendroglial Tumors. (harvard.edu)
  • A human BRCA2 complex containing a structural DNA binding component influences cell cycle progression. (embl-heidelberg.de)
  • Importantly, antibody microinjection experiments suggest a role for BRCA2/BRAF35 complex in modulation of cell cycle progression. (embl-heidelberg.de)
  • The cyclin B-Ub ligase, also termed the cyclosome or anaphase-promoting complex (APC), has recently been isolated and shown to be required for cyclin B ubiquitination in vitro ( 8 - 10 ). (pnas.org)
  • and ( iii ) MAD2 generates these effects by inhibiting the Ub ligase activity of the cyclosome. (pnas.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)
  • Ub is then transferred to a Ub-conjugating protein (E2) and finally that protein complex is recognized by a Ub-protein ligase (E3). (wikibooks.org)
  • Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control, DNA damage response and translesion DNA synthesis. (abcam.com)
  • In biochemical terms, the SAC acts by inhibiting the Cdc20-bound form of the anaphase-promoting complex/cyclosome (APC/C), a large ubiquitin protein ligase ( Peters, 2006 ). (pubmedcentralcanada.ca)
  • Inhibition of the anaphase-promoting complex by the Xnf7 ubiquitin ligase. (duke.edu)
  • Tripartite motif 39 (Trim39) is a RING domain-containing E3 ubiquitin ligase able to inhibit the anaphase-promoting complex (APC/C) directly. (duke.edu)
  • Most of the characterized FBPs are components of the SCF (SKp1, Cullin, F-box protein) E3 ubiquitin-ligase complex. (mdpi.com)
  • The encoded protein is evolutionarily conserved and is required for the integrity and ubiquitin ligase activity of the anaphase promoting complex. (antikoerper-online.de)
  • CDC20_HUMAN ] Required for full ubiquitin ligase activity of the anaphase promoting complex/cyclosome (APC/C) and may confer substrate specificity upon the complex. (proteopedia.org)
  • 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)
  • Cdk1, som er også kendt som celledeling cyklus protein 2 homolog (cdc2) er en master controller til cellecyklus i alle eukaryoter 1 , 2 , 3 , 4 , 5 , og phosphorylates en anslåede 8-13% af proteomet 6 , 7 . (jove.com)
  • These progenitors are unique to the second tracheal metamere as homologous cells from other segments, express fizzy-related (fzr) , the Drosophila homolog of CDH1 protein of the APC complex , and enter endocycle and do not contribute to adult trachea. (sdbonline.org)
  • Given that Mad1:Mad2 is a stable complex and Cdc20 and Mad1 bind Mad 2 in the very same binding site, it is highly unlikely that Closed Mad2 releases Mad1 to bind Cdc20. (wikipedia.org)
  • A model, which accounts for Mad2 adopting a conformation capable of binding Cdc20, relies upon the formation of Mad1-Mad2 core complex first. (wikipedia.org)
  • The MCC inhibits the anaphase-promoting complex/cyclosome (APC/C) and leads to cell cycle arrest. (atlasgeneticsoncology.org)
  • The enzyme binds an ATP-activated Ub complex where a transfer of the Ub to the a cysteine residue on E1 forms the thioester bond and releases AMP. (wikibooks.org)
  • The complex then binds the particular protein and the E2-Ub complex, facilitating the transfer of Ub to tag the protein. (wikibooks.org)
  • ANAPC5 (Anaphase Promoting Complex Subunit 5) is a Protein Coding gene. (genecards.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)
  • Antigen standard for anaphase promoting complex subunit 11 (ANAPC11), transcript variant 1 is a lysate prepared from HEK293T cells transiently transfected with a TrueORF gene-carrying pCMV plasmid and then lysed in RIPA Buffer. (creativebiomart.net)
  • The mechanism by which TPX2 promotes microtubule nucleation has yet to be determined. (wikipedia.org)
  • Emi2-mediated inhibition of E2-substrate ubiquitin transfer by the anaphase-promoting complex/cyclosome through a D-box-independent mechanism. (duke.edu)
  • Targeting the anaphase promoting complex: common pathways for viral infection and cancer therapy. (biomedsearch.com)
  • however, when inhibition is relieved, activated separase cleaves the cohesin complex which links the sister chromatids together. (wikipedia.org)
  • Furthermore, we show that ZPc domain function requires cleavage at the LET-653 C-terminus, likely in part to relieve inhibition of the ZPc by the ZPn domain, but also to promote some other aspect of ZPc domain function. (prolekare.cz)
  • LOCUS NP_001131136 537 aa linear PRI 20-JUN-2020 DEFINITION anaphase-promoting complex subunit 7 isoform b [Homo sapiens]. (genome.jp)
  • J. 449 (2), 365-371 (2013) PUBMED 23078409 REMARK GeneRIF: Data indicate that additional density present in the anaphase-promoting complex (APC/C) structure, proximal to Apc3/Cdc27 of the (tetratricopeptide repeat) lobe, is assigned to the TPR subunit Apc7, a subunit specific to vertebrate APC/C. REFERENCE 6 (residues 1 to 537) AUTHORS Sudakin V, Chan GK and Yen TJ. (genome.jp)
  • Here we show that this G2 arrest is due to loss of nimA function and that it is dependent on BIMAAPC3, a component of the anaphase promoting complex/cyclosome (APC/C). Whereas nimA single mutants arrested in G2 with decondensed chromatin and interphase microtubule arrays, nimA, bimAAPC3 double mutants arrested growth with condensed chromatin and aster-like microtubule arrays. (uky.edu)
  • Six ATPases are required for the regulatory complex to function: ATP hydrolysis likely causes a conformational change in the 19S subunit which is transferred to the 20S subunit, allowing the active site to become available for substrate binding. (wikibooks.org)
  • In this review, I summarize what is known about how the APC/C selects its targets during mitotic exit and review the evidence that substrate targeting after anaphase onset may be required for the correct execution of events at this time in the cell cycle. (portlandpress.com)
  • The cyclosome is a large protein complex with a sedimentation coefficient of 20 S in Xenopus eggs and clam oocytes and 36 S in budding yeast ( 8 , 9 , 11 , 12 ). (pnas.org)
  • In addition to hZw10, we have found that hZwint-1 interacts with components of the conserved Ndc80 and Mis12 complexes in yeast two-hybrid and GST (glutathione transferase) pull-down assays. (biochemj.org)
  • CDK1 activity decreases abruptly at anaphase onset, and the phosphatases that oppose it increase in activity ( 5 ). (mcponline.org)
  • Sammen præsentere disse protokoller en meget kraftfuld tilgang, der giver Cdk1-specifikke fosforylering websteder og muliggør Mekanistiske undersøgelser i hvordan Cdk1 kontrol af cellecyklus. (jove.com)
  • I denne analyse, er kommercielt tilgængelige menneskelige Cdk1/cyclin B bruges til at phosphorylate en renset target protein in vitro . (jove.com)
  • Once cyclinB1-Cdk1 complex is activated, the circuit drives a set of mitotic events including chromosome condensation and nuclear envelope breakdown (NEB). (elifesciences.org)
  • Interacts with anaphase promoting complex/cyclosome ( APC /C). Interacts with CDC20 and FZR1 . (rcsb.org)
  • Title: Sumoylation promotes optimal APC/C Activation and Timely Anaphase. (nih.gov)
  • Entrance into anaphase is mediated by APCCdc20 activation. (wikipedia.org)
  • Proapoptotic Bcl-2 family members, such as Bax, promote release of cytochrome c from mitochondria, leading to caspase activation and cell death. (duke.edu)
  • Genetic alterations to components of these E3 complexes that result in loss of function (such as FBW7, CDH1 and CDC20) or gain of function (such as SKP2 and β-transducin repeat-containing protein (β-TrCP)) are implicated in the development of cancer. (nature.com)
  • TITLE Expression of the CDH1-associated form of the anaphase-promoting complex in postmitotic neurons JOURNAL Proc. (genome.jp)
  • Here, we report that PSMA is localized to a membrane compartment in the vicinity of mitotic spindle poles and associates with the anaphase-promoting complex (APC). (aacrjournals.org)
  • The APC (anaphase-promoting complex) or cyclosome is a large multisubunit protein complex. (portlandpress.com)
  • The Anaphase Promoting Complex/Cyclosome is regulated by sumoylation to ensure timely mitotic exit in human cells. (elifesciences.org)