Spindle Apparatus: A microtubule structure that forms during CELL DIVISION. It consists of two SPINDLE POLES, and sets of MICROTUBULES that may include the astral microtubules, the polar microtubules, and the kinetochore microtubules.Anaphase: The phase of cell nucleus division following METAPHASE, in which the CHROMATIDS separate and migrate to opposite poles of the spindle.Anaphase-Promoting Complex-Cyclosome: An E3 ubiquitin ligase primarily involved in regulation of the metaphase-to-anaphase transition during MITOSIS through ubiquitination of specific CELL CYCLE PROTEINS. Enzyme activity is tightly regulated through subunits and cofactors, which modulate activation, inhibition, and substrate specificity. The anaphase-promoting complex, or APC-C, is also involved in tissue differentiation in the PLACENTA, CRYSTALLINE LENS, and SKELETAL MUSCLE, and in regulation of postmitotic NEURONAL PLASTICITY and excitability.Ubiquitin-Protein Ligase Complexes: Complexes of enzymes that catalyze the covalent attachment of UBIQUITIN to other proteins by forming a peptide bond between the C-terminal GLYCINE of UBIQUITIN and the alpha-amino groups of LYSINE residues in the protein. The complexes play an important role in mediating the selective-degradation of short-lived and abnormal proteins. The complex of enzymes can be broken down into three components that involve activation of ubiquitin (UBIQUITIN-ACTIVATING ENZYMES), conjugation of ubiquitin to the ligase complex (UBIQUITIN-CONJUGATING ENZYMES), and ligation of ubiquitin to the substrate protein (UBIQUITIN-PROTEIN LIGASES).Kinetochores: Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle.Mitosis: A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.M Phase Cell Cycle Checkpoints: The cellular signaling system that halts the progression of cells through MITOSIS or MEIOSIS if a defect that will affect CHROMOSOME SEGREGATION is detected.Mad2 Proteins: Mad2 is a component of the spindle-assembly checkpoint apparatus. It binds to and inhibits the Cdc20 activator subunit of the anaphase-promoting complex, preventing the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. Mad2 is required for proper microtubule capture at KINETOCHORES.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.Cdc20 Proteins: Highly conserved proteins that specifically bind to and activate the anaphase-promoting complex-cyclosome, promoting ubiquitination and proteolysis of cell-cycle-regulatory proteins. Cdc20 is essential for anaphase-promoting complex activity, initiation of anaphase, and cyclin proteolysis during mitosis.Anaphase-Promoting Complex-Cyclosome: An E3 ubiquitin ligase primarily involved in regulation of the metaphase-to-anaphase transition during MITOSIS through ubiquitination of specific CELL CYCLE PROTEINS. Enzyme activity is tightly regulated through subunits and cofactors, which modulate activation, inhibition, and substrate specificity. The anaphase-promoting complex, or APC-C, is also involved in tissue differentiation in the PLACENTA, CRYSTALLINE LENS, and SKELETAL MUSCLE, and in regulation of postmitotic NEURONAL PLASTICITY and excitability.Ubiquitin-Protein Ligase Complexes: Complexes of enzymes that catalyze the covalent attachment of UBIQUITIN to other proteins by forming a peptide bond between the C-terminal GLYCINE of UBIQUITIN and the alpha-amino groups of LYSINE residues in the protein. The complexes play an important role in mediating the selective-degradation of short-lived and abnormal proteins. The complex of enzymes can be broken down into three components that involve activation of ubiquitin (UBIQUITIN-ACTIVATING ENZYMES), conjugation of ubiquitin to the ligase complex (UBIQUITIN-CONJUGATING ENZYMES), and ligation of ubiquitin to the substrate protein (UBIQUITIN-PROTEIN LIGASES).Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes (GENES, MOS). They function in the cell cycle to maintain MATURATION PROMOTING FACTOR in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time.Cyclin B: A cyclin subtype that is transported into the CELL NUCLEUS at the end of the G2 PHASE. It stimulates the G2/M phase transition by activating CDC2 PROTEIN KINASE.CDC2 Protein Kinase: Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.Cyclin B1: A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.Xenopus: An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.Protein Subunits: Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.Mitosis: A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.Xenopus laevis: The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.Plant Leaves: Expanded structures, usually green, of vascular plants, characteristically consisting of a bladelike expansion attached to a stem, and functioning as the principal organ of photosynthesis and transpiration. (American Heritage Dictionary, 2d ed)Arabidopsis Proteins: Proteins that originate from plants species belonging to the genus ARABIDOPSIS. The most intensely studied species of Arabidopsis, Arabidopsis thaliana, is commonly used in laboratory experiments.Arabidopsis: A plant genus of the family BRASSICACEAE that contains ARABIDOPSIS PROTEINS and MADS DOMAIN PROTEINS. The species A. thaliana is used for experiments in classical plant genetics as well as molecular genetic studies in plant physiology, biochemistry, and development.Gene Expression Regulation, Plant: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in plants.Plants, Genetically Modified: PLANTS, or their progeny, whose GENOME has been altered by GENETIC ENGINEERING.Anaphase-Promoting Complex-Cyclosome: An E3 ubiquitin ligase primarily involved in regulation of the metaphase-to-anaphase transition during MITOSIS through ubiquitination of specific CELL CYCLE PROTEINS. Enzyme activity is tightly regulated through subunits and cofactors, which modulate activation, inhibition, and substrate specificity. The anaphase-promoting complex, or APC-C, is also involved in tissue differentiation in the PLACENTA, CRYSTALLINE LENS, and SKELETAL MUSCLE, and in regulation of postmitotic NEURONAL PLASTICITY and excitability.Genes, Plant: The functional hereditary units of PLANTS.Plant Roots: The usually underground portions of a plant that serve as support, store food, and through which water and mineral nutrients enter the plant. (From American Heritage Dictionary, 1982; Concise Dictionary of Biology, 1990)Droughts: Prolonged dry periods in natural climate cycle. They are slow-onset phenomena caused by rainfall deficit combined with other predisposing factors.Crops, Agricultural: Cultivated plants or agricultural produce such as grain, vegetables, or fruit. (From American Heritage Dictionary, 1982)Anaphase-Promoting Complex-Cyclosome: An E3 ubiquitin ligase primarily involved in regulation of the metaphase-to-anaphase transition during MITOSIS through ubiquitination of specific CELL CYCLE PROTEINS. Enzyme activity is tightly regulated through subunits and cofactors, which modulate activation, inhibition, and substrate specificity. The anaphase-promoting complex, or APC-C, is also involved in tissue differentiation in the PLACENTA, CRYSTALLINE LENS, and SKELETAL MUSCLE, and in regulation of postmitotic NEURONAL PLASTICITY and excitability.Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.Ubiquitin-Protein Ligase Complexes: Complexes of enzymes that catalyze the covalent attachment of UBIQUITIN to other proteins by forming a peptide bond between the C-terminal GLYCINE of UBIQUITIN and the alpha-amino groups of LYSINE residues in the protein. The complexes play an important role in mediating the selective-degradation of short-lived and abnormal proteins. The complex of enzymes can be broken down into three components that involve activation of ubiquitin (UBIQUITIN-ACTIVATING ENZYMES), conjugation of ubiquitin to the ligase complex (UBIQUITIN-CONJUGATING ENZYMES), and ligation of ubiquitin to the substrate protein (UBIQUITIN-PROTEIN LIGASES).Apc5 Subunit, Anaphase-Promoting Complex-Cyclosome: A subunit of the anaphase-promoting complex whose primary function is to provide structural support for the catalytic and substrate-recognition modules of the complex. Apc5, along with Apc4, tethers the tetratricopeptide-coactivator binding subcomplex to the main structural subunit, Apc1.Cdc20 Proteins: Highly conserved proteins that specifically bind to and activate the anaphase-promoting complex-cyclosome, promoting ubiquitination and proteolysis of cell-cycle-regulatory proteins. Cdc20 is essential for anaphase-promoting complex activity, initiation of anaphase, and cyclin proteolysis during mitosis.Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome: A highly evolutionarily conserved subunit of the anaphase-promoting complex (APC-C) containing multiple 34-amino-acid tetratricopeptide repeats. These domains, also found in Apc subunits 6, 7, and 8, have been shown to mediate protein-protein interactions, suggesting that Apc3 may assist in coordinating the juxtaposition of the catalytic and substrate recognition module subunits relative to co-activators and APC-C inhibitors.Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome: The largest subunit of the anaphase-promoting complex. It acts primarily as a scaffold for the proper organization and arrangement of subunits. The C-terminal region of Apc1 contains a series of tandem amino acid repeats that are also seen in the 26S proteasome regulatory particle, and may assist with forming and stabilizing protein-protein interactions.Cdh1 Proteins: Cdh1 is an activator of the anaphase-promoting complex-cyclosome, and is involved in substrate recognition. It associates with the complex in late MITOSIS from anaphase through G1 to regulate activity of CYCLIN-DEPENDENT KINASES and to prevent premature DNA replication.Databases, Protein: Databases containing information about PROTEINS such as AMINO ACID SEQUENCE; PROTEIN CONFORMATION; and other properties.Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome: A highly conserved subunit of the anaphase-promoting complex (APC-C) containing multiple 34-amino-acid tetratricopeptide repeats. These domains, also found in Apc3, Apc6, and Apc7, have been shown to mediate protein-protein interactions, suggesting that Apc8 may assist in coordinating the juxtaposition of the catalytic and substrate recognition module subunits relative to coactivators and APC-C inhibitors.Anaphase-Promoting Complex-Cyclosome: An E3 ubiquitin ligase primarily involved in regulation of the metaphase-to-anaphase transition during MITOSIS through ubiquitination of specific CELL CYCLE PROTEINS. Enzyme activity is tightly regulated through subunits and cofactors, which modulate activation, inhibition, and substrate specificity. The anaphase-promoting complex, or APC-C, is also involved in tissue differentiation in the PLACENTA, CRYSTALLINE LENS, and SKELETAL MUSCLE, and in regulation of postmitotic NEURONAL PLASTICITY and excitability.Ubiquitin-Protein Ligase Complexes: Complexes of enzymes that catalyze the covalent attachment of UBIQUITIN to other proteins by forming a peptide bond between the C-terminal GLYCINE of UBIQUITIN and the alpha-amino groups of LYSINE residues in the protein. The complexes play an important role in mediating the selective-degradation of short-lived and abnormal proteins. The complex of enzymes can be broken down into three components that involve activation of ubiquitin (UBIQUITIN-ACTIVATING ENZYMES), conjugation of ubiquitin to the ligase complex (UBIQUITIN-CONJUGATING ENZYMES), and ligation of ubiquitin to the substrate protein (UBIQUITIN-PROTEIN LIGASES).Securin: Securin is involved in the control of the metaphase-anaphase transition during MITOSIS. It promotes the onset of anaphase by blocking SEPARASE function and preventing proteolysis of cohesin and separation of sister CHROMATIDS. Overexpression of securin is associated with NEOPLASTIC CELL TRANSFORMATION and tumor formation.S Phase: Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.Cdc20 Proteins: Highly conserved proteins that specifically bind to and activate the anaphase-promoting complex-cyclosome, promoting ubiquitination and proteolysis of cell-cycle-regulatory proteins. Cdc20 is essential for anaphase-promoting complex activity, initiation of anaphase, and cyclin proteolysis during mitosis.Cyclin B: A cyclin subtype that is transported into the CELL NUCLEUS at the end of the G2 PHASE. It stimulates the G2/M phase transition by activating CDC2 PROTEIN KINASE.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Cdh1 Proteins: Cdh1 is an activator of the anaphase-promoting complex-cyclosome, and is involved in substrate recognition. It associates with the complex in late MITOSIS from anaphase through G1 to regulate activity of CYCLIN-DEPENDENT KINASES and to prevent premature DNA replication.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.Cyclins: A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.Spindle Apparatus: A microtubule structure that forms during CELL DIVISION. It consists of two SPINDLE POLES, and sets of MICROTUBULES that may include the astral microtubules, the polar microtubules, and the kinetochore microtubules.Meiosis: A type of CELL NUCLEUS division, occurring during maturation of the GERM CELLS. Two successive cell nucleus divisions following a single chromosome duplication (S PHASE) result in daughter cells with half the number of CHROMOSOMES as the parent cells.Kinetochores: Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle.Mitosis: A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.M Phase Cell Cycle Checkpoints: The cellular signaling system that halts the progression of cells through MITOSIS or MEIOSIS if a defect that will affect CHROMOSOME SEGREGATION is detected.Chromosome Segregation: The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS.Mad2 Proteins: Mad2 is a component of the spindle-assembly checkpoint apparatus. It binds to and inhibits the Cdc20 activator subunit of the anaphase-promoting complex, preventing the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. Mad2 is required for proper microtubule capture at KINETOCHORES.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.Developmental Biology: The field of biology which deals with the process of the growth and differentiation of an organism.Metaphase: The phase of cell nucleus division following PROMETAPHASE, in which the CHROMOSOMES line up across the equatorial plane of the SPINDLE APPARATUS prior to separation.Kinetochores: Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle.Spindle Apparatus: A microtubule structure that forms during CELL DIVISION. It consists of two SPINDLE POLES, and sets of MICROTUBULES that may include the astral microtubules, the polar microtubules, and the kinetochore microtubules.Metaphase: The phase of cell nucleus division following PROMETAPHASE, in which the CHROMOSOMES line up across the equatorial plane of the SPINDLE APPARATUS prior to separation.Chromosome Segregation: The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS.Anaphase: The phase of cell nucleus division following METAPHASE, in which the CHROMATIDS separate and migrate to opposite poles of the spindle.Mitosis: A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS.Mad2 Proteins: Mad2 is a component of the spindle-assembly checkpoint apparatus. It binds to and inhibits the Cdc20 activator subunit of the anaphase-promoting complex, preventing the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. Mad2 is required for proper microtubule capture at KINETOCHORES.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.Meiosis: A type of CELL NUCLEUS division, occurring during maturation of the GERM CELLS. Two successive cell nucleus divisions following a single chromosome duplication (S PHASE) result in daughter cells with half the number of CHROMOSOMES as the parent cells.ArchivesBiological Science Disciplines: All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from BIOLOGY, one of its subdivisions, concerned specifically with the origin and life processes of living organisms.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.PubMed: A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.Directories as Topic: Lists of persons or organizations, systematically arranged, usually in alphabetic or classed order, giving address, affiliations, etc., for individuals, and giving address, officers, functions, and similar data for organizations. (ALA Glossary of Library and Information Science, 1983)Scandium: Scandium. An element of the rare earth family of metals. It has the atomic symbol Sc, atomic number 21, and atomic weight 45.Mitosis: A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.Serial Publications: Publications in any medium issued in successive parts bearing numerical or chronological designations and intended to be continued indefinitely. (ALA Glossary of Library and Information Science, 1983, p203)Interphase: The interval between two successive CELL DIVISIONS during which the CHROMOSOMES are not individually distinguishable. It is composed of the G phases (G1 PHASE; G0 PHASE; G2 PHASE) and S PHASE (when DNA replication occurs).Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.Protein Phosphatase 1: A eukayrotic protein serine-threonine phosphatase subtype that dephosphorylates a wide variety of cellular proteins. The enzyme is comprised of a catalytic subunit and regulatory subunit. Several isoforms of the protein phosphatase catalytic subunit exist due to the presence of multiple genes and the alternative splicing of their mRNAs. A large number of proteins have been shown to act as regulatory subunits for this enzyme. Many of the regulatory subunits have additional cellular functions.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Cyclin-Dependent Kinase 2: A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.Cyclins: A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.Cyclin A: A cyclin subtype that has specificity for CDC2 PROTEIN KINASE and CYCLIN-DEPENDENT KINASE 2. It plays a role in progression of the CELL CYCLE through G1/S and G2/M phase transitions.Cyclin D1: Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.Kinetochores: Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle.Spindle Apparatus: A microtubule structure that forms during CELL DIVISION. It consists of two SPINDLE POLES, and sets of MICROTUBULES that may include the astral microtubules, the polar microtubules, and the kinetochore microtubules.Mitosis: A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.Mad2 Proteins: Mad2 is a component of the spindle-assembly checkpoint apparatus. It binds to and inhibits the Cdc20 activator subunit of the anaphase-promoting complex, preventing the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. Mad2 is required for proper microtubule capture at KINETOCHORES.Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS.ran GTP-Binding Protein: A monomeric GTP-binding protein involved in nucleocytoplasmic transport of proteins into the nucleus and RNA into the cytoplasm. This enzyme was formerly listed as EC 3.6.1.47.M Phase Cell Cycle Checkpoints: The cellular signaling system that halts the progression of cells through MITOSIS or MEIOSIS if a defect that will affect CHROMOSOME SEGREGATION is detected.Chromosome Segregation: The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS.Metaphase: The phase of cell nucleus division following PROMETAPHASE, in which the CHROMOSOMES line up across the equatorial plane of the SPINDLE APPARATUS prior to separation.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.

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)

*APC/C activator protein CDH1

The anaphase-promoting complex/cyclosome (APC/c) is an ubiquitin E3-ligase complex. Once activated it attaches chains of ... Peters JM (2006). "The anaphase promoting complex/cyclosome: a machine designed to destroy". Nat. Rev. Mol. Cell Biol. 7 (9): ... Manchado E, Eguren M, Malumbres M (2010). "The anaphase-promoting complex/cyclosome (APC/C): cell-cycle-dependent and - ... Li M, Shin YH, Hou L, Huang X, Wei Z, Klann E, Zhang P (2008). "The adaptor protein of the anaphase promoting complex Cdh1 is ...

*Mad2

"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 ...

*TPX2

Stewart S, Fang G (2005). "Anaphase-promoting complex/cyclosome controls the stability of TPX2 during mitotic exit". Mol. Cell ...

*Spindle poison

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 ...

*MDC1

"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 ...

*FBXO5

Lehman NL, Verschuren EW, Hsu JY, Cherry AM, Jackson PK (2006). "Overexpression of the anaphase promoting complex/cyclosome ... a regulator of the anaphase promoting complex/cyclosome". Proc. Natl. Acad. Sci. U.S.A. 101 (21): 7937-42. doi:10.1073/pnas. ... "Emi1 stably binds and inhibits the anaphase-promoting complex/cyclosome as a pseudosubstrate inhibitor". Genes Dev. 20 (17): ... Hansen DV, Loktev AV, Ban KH, Jackson PK (2005). "Plk1 Regulates Activation of the Anaphase Promoting Complex by ...

*Glypican

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 ...

*Endoreduplication

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 ...

*BUB1

"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, ...

*ANAPC2

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 ...

*Jan-Michael Peters

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 ...

*BUB3

... forms a complex with BUB1 (BUB1/BUB3 complex) to inhibit the anaphase-promoting complex or cyclosome (APC/C) as soon as ... 2008). "Two different mitotic checkpoint inhibitors of the anaphase-promoting complex/cyclosome antagonize the action of the ... inhibit the action of the Anaphase Promoting Complex (APC), preventing early anaphase entry and mitotic exit; this serves as a ... Fang G, Yu H & Kirschner MW (1998). "Direct binding of CDC20 protein family members activates the anaphase-promoting complex in ...

*Conly Rieder

The END network couples spindle pole assembly to inhibition of the anaphase-promoting complex/cyclosome in early mitosis. ...

*ANLN

doi: 10.1016/j.cub.2007.11.050 Zhao, W. M., & Fang, G. (2005). Anillin is a substrate of anaphase-promoting complex/cyclosome ( ... 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 ...

*CDC27

"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 ...

*PABPC1

"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 ...

*ANAPC5

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 ...

*Mad1

... and inhibits the metaphase to anaphase transition by preventing the activation of the anaphase-promoting complex/cyclosome (APC ... Thereby it inhibits the activity of the anaphase-promoting complex/cyclosome (APC/C). Homolog's of Mad1 are conserved in ... The spindle assembly checkpoint inhibits the activity of the anaphase promoting complex by preventing degradation of downstream ... Mad1 recruits the anaphase inhibitor Mad2 to unattached kinetochores and is essential for Mad2-Cdc20 complex formation in vivo ...

*Cullin

... 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 ...

*CDC16

"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 ...

*MAD2L1

"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 ...

*Spindle checkpoint

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 ... thereby preventing the activation of the polyubiquitylation activities of anaphase promoting complex (APC). The proteins ...

*Anaphase-promoting complex

... (also called the cyclosome or APC/C) is an E3 ubiquitin ligase that marks target cell cycle proteins ... anaphase-promoting complex at the US National Library of Medicine Medical Subject Headings (MeSH) 3D electron microscopy ... Review) Harper JW, Burton JL, Solomon MJ (September 2002). "The anaphase-promoting complex: it's not just for mitosis any more ... Zachariae W, Nasmyth K (August 1999). "Whose end is destruction: cell division and the anaphase-promoting complex". Genes Dev. ...

*SCF complex

The anaphase-promoting complex or cyclosome (APC/C) controls the metaphase-anaphase transition when bound to its substrate- ... Skp, Cullin, F-box containing complex (or SCF complex) is a multi-protein E3 ubiquitin ligase complex catalyzing the ... Therefore, SCF-Skp2 promotes cell-cycle progression and cell growth. On the other hand, SCF-βTrCP promotes proteolysis of Emi1 ... Two F-box-protein-bound SCF complexes (SCF-Skp2 and SCF-β-TrCP), are most well studied among over 70 F-box proteins identified ...

*BUB1B

... 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 ...

*ANAPC7

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 ... Park KH, Choi SE, Eom M, Kang Y (2006). "Downregulation of the anaphase-promoting complex (APC)7 in invasive ductal carcinomas ... 1999). "Characterization of the DOC1/APC10 subunit of the yeast and the human anaphase-promoting complex". J. Biol. Chem. 274 ( ...
Weblio英和和英辞典の索引「A」157ページ目。例えば、anaphase-promoting complex、anaphase-promoting complex Cdh1 subunit、Anaphase-promoting complex subunit 1、Anaphase-promoting complex subunit 10、Anaphase-promoting complex subunit 11、Anaphase-promoting complex subunit 13、Anaphase-promoting complex subunit 14、Anaphase-promoting complex subunit 15、Anaphase-promoting complex subunit 2、Anaphase-promoting complex subunit 3、などの用語があります。
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 ...
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 ...
Proteolysis controls key transitions at several points in the cell cycle. In mitosis, the activation of a large ubiquitin-protein ligase, the anaphase-promoting complex (APC), is required for anaphase initiation and for exit from mitosis. We show that APC is under complex control by a network of regulatory factors, CDC20, CDH1 and MAD2. CDC20 and CDH1 are activators of APC; they bind directly to APC and activate its cyclin ubiquitination activity. CDC20 activates APC at the onset of anaphase in a destruction box (DB)-dependent manner, while CDH1 activates APC from late anaphase through G1 with apparently a much relaxed specificity for the DB. Therefore, CDC20 and CDH1 control both the temporal order of activation and the substrate specificity of APC, and hence regulate different events during mitosis and G1. Counteracting the effect of CDC20, the checkpoint protein MAD2 acts as an inhibitor of APC. When the spindle-assembly checkpoint is activated, MAD2 forms a ternary complex with CDC20 and APC ...
Unidirectional and irreversible progression through the cell cycle is mediated through the selective proteolytic regulation of both positive and negative regulators of cyclin-dependent kinases (CDKs). Cyclins, cell cycle inhibitors, and many other proteins are marked with ubiquitin by E3 ubiquitin ligases and, subsequently, recognized and destroyed by the 26S proteasome (Hershko, 1997; Peters, 2002). Two related E3 ubiquitin-ligase complexes are most intimately dedicated to basic cell cycle regulation, namely Skp1-Cullin-F-box (SCF)-related complexes and the anaphase-promoting complex/cyclosome (APC/C), which operate at the G1-to-S transition and in the M-G1 phases, respectively (Marrocco et al., 2010).. The APC/C is a multisubunit complex that is highly conserved among eukaryotes, consisting of at least 11 different subunits, including a catalytic core composed of APC2 and APC11 (Page and Hieter, 1999; Tang et al., 2001). Besides this core, the APC/C requires essential subunits for its ...
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 regulation of canonical mitotic cell cycles is well understood, but the basic principles of the rapid, synchronized early mitotic divisions in embryos remain a mystery. Early embryos lack key mitotic regulators, such as checkpoints, the anaphase-promoting complex/cyclosome (APC/C)-inhibitory protein Emi1, and the inhibitory phosphorylations of cyclin-dependent kinase 1 (Cdk1). Working in Xenopus embryos, Tischer et al. identified XErp1 (also known as Emi2) as a mitotic APC/C-inhibitor essential for early mitotic divisions. The mitotic APC/C-inhibitory activity of XErp1 is positively regulated by protein kinase A (PKA) and protein phosphatase IIA (PP2A), which antagonizes Cdk1s inhibitory effect on XErp1. Thus, Cdk1 and PP2A/PKA appear to act antagonistically to control XErp1 activity, which results in the oscillatory activation and inactivation of the APC/C required for fast and synchronous mitotic divisions.. T. Tischer, E. Hörmanseder, T. U. Mayer, The APC/C inhibitor XErp1/Emi2 is ...
Ziguo Zhang, Kiran Kulkarni, Sarah J Hanrahan, Andrew J Thompson, David Barford. EMBO J., 2010 Nov 3 , 29, 3733-44. The anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase responsible for controlling cell cycle transitions, is a multisubunit complex assembled from 13 different proteins. Numerous APC/C subunits incorporate multiple copies of the tetratricopeptide repeat (TPR). Here, we report the crystal structure of Schizosaccharomyces pombe Cut9 (Cdc16/Apc6) in complex with Hcn1 (Cdc26), showing that Cdc16/Cut9 is a contiguous TPR superhelix of 14 TPR units. A C-terminal block of TPR motifs interacts with Hcn1, whereas an N-terminal TPR block mediates Cdc16/Cut9 self-association through a homotypic interface. This dimer interface is structurally related to the N-terminal dimerization domain of Cdc27, demonstrating that both Cdc16/Cut9 and Cdc27 form homo-dimers through a conserved mechanism. The acetylated N-terminal Met residue of Hcn1 is enclosed within a chamber created from ...
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 ...
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. ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
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, ...
1GQP: Implications for the Ubiquitination Reaction of the Anaphase-Promoting Complex from the Crystal Structure of the Doc1/Apc10 Subunit.
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.
Mitotic divisions result from the oscillating activity of cyclin-dependent kinase-1 (Cdk1). Cdk1 activity is terminated by the anaphase-promoting-complex/cyclosome (APC/C), a ubiquitin-ligase that targets cyclin-B for destruction. In somatic divisions, Emi1 and the spindle-assembly-checkpoint (SAC) regulate cell-cycle progression by inhibiting the APC/C. Early embryonic divisions lack these APC/C-inhibitory components, raising the question of how these cycles are controlled. Here, we found that the APC/C-inhibitory activity of XErp1/Emi2 was essential for early divisions in Xenopus embryos. Loss of XErp1 resulted in untimely destruction of APC/C-substrates and embryonic lethality. XErp1s APC/C-inhibitory function was negatively regulated by Cdk1 and positively by protein-phosphatase-2A (PP2A). Thus, Cdk1 and PP2A are at the core of early mitotic cell-cycles by antagonistically controlling XErp1-activity resulting in oscillating APC/C activity.. ...
The E3 ubiquitin ligase Anaphase Promoting Complex/Cyclosome (APC/C) regulates important processes in cells, such as the cell cycle, by targeting a set of substrates for degradation. In the last decade, APC/C has been related to several major functions in the nervous system, including axon guidance, synaptic plasticity, neurogenesis, and neuronal survival. Interestingly, some of the identified APC/C substrates have been related to neurodegenerative diseases. There is an accumulation of some degradation targets of APC/C in Alzheimers disease (AD) brains, which suggests a dysregulation of the protein complex in the disorder. Moreover, recently evidence has been provided for an inactivation of APC/C in AD. It has been shown that oligomers of the AD-related peptide, Aβ, induce degradation of the APC/C activator subunit cdh1, in vitro in neurons in culture and in vivo in the mouse hippocampus. Furthermore, in the AD mouse model APP/PS1, lower cdh1 levels were observed in pyramidal neurons in CA1 when
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 ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
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 ...
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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. ...
Subunit Of The Anaphase-Promoting Complex/Cyclosome (APC/C); Which Is A Ubiquitin-protein Ligase Required For Degradation Of Anaphase Inhibitors, Including Mitotic Cyclins, During The Metaphase/anaphase Transition; Component Of The Catalytic Core Of The APC/C; Has Similarity To Cullin Cdc53p
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 ...
As a critical ubiquitin ligase, the anaphase-promoting complex/cyclosome (APC/C) governs cell cycle progression, signaling modulation and the pathogenesis of some human diseases. Recent studies implicate APC in maintaining genomic integrity, but the mechanism by which it plays such a role remains largely unknown. We report here that acute UV radiation triggers proteolysis of CDH1, an activator of APC, which is involved in regulation of apoptosis induced by UV radiation. Depletion of CDH1 by RNA interference enhances the cellular susceptibility to apoptosis in response to UV radiation, whereas overexpression of non-degradable CDH1 delays UV radiation-induced apoptosis. In addition, UV-induced degradation of CDH1 results in the accumulation of cyclin B1 and therefore to increased CDK1 activity, which is believed to enhance UV-induced apoptosis. The present results unveil a novel role for the APC in UV-induced cell death and demonstrate a new regulatory mechanism for APC/CDH1 through proteolysis. ...
Pre-RC assembly is restricted to late M/early G1 phase by at least three separate systems in eukaryotes. In some organisms, all three are used, whereas in others only one or two. These systems include geminin-dependent inhibition of Cdt1 function, Cul4 (Crl4)- and proliferating cell nuclear antigen (PCNA)-dependent degradation of Cdt1 during S phase and cyclin-dependent kinase (CDK)-dependent inhibition of licensing via a variety of targets. These have been the subject of a number of very thorough reviews and the reader is encouraged to consult these for more detail [1-4,6-8,47-49].. Geminin is a small, coiled-coil protein originally identified in Xenopus egg extracts as a substrate for the anaphase-promoting complex/cyclosome (APC/C) [50] and an inhibitor of Cdt1 function in licensing [51,52]. Because the APC/C is specifically active during mitosis and G1 phase, geminin is inactivated during this period, allowing Cdt1 to participate in the licensing reaction only during this period. Geminin ...
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 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 ...
Harvard Medical School. Specificity, Efficiency and Processivity in the Eukaryotic Protein Degradation System. Recommended Readings. Lu, Y., Lee, B. H., King, R. W., Finley, D., & Kirschner, M. W. (2015). Substrate degradation by the proteasome: A single-molecule kinetic analysis. Science, 348(6231), 1250834. doi: 10.1126/science.1250834.. Lu, Y., Wang, W., & Kirschner, M. W. (2015). Specificity of the anaphase-promoting complex: A single-molecule study. Science, 348(6231), 1248737. doi: 10.1126/science.1248737. ...
Discover Lifes page about the biology, natural history, ecology, identification and distribution of Childs, Ken I_KEN/0002 -- Discover Life
Lala Kent has always been candid about her struggles with substance abuse, but last month she opened up about her struggle with alcoholism -what shes doing about it. Five months ago, I came to the realization that I am an alcoholic, and I am now a friend of Bill W., Kent said on Instagram. In an interview with
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Ad Age Editor Ken Wheaton writes that pharmaceutical marketers might end up on the wrong end of regulation if they dont rein in their excesses.
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In addition to inhibiting APC/CCdc20 by blocking substrate recruitment, Mad3 also destabilizes Cdc20 in a spindle checkpoint-dependent manner [64]. King et al. demonstrated that destabilization of Cdc20 requires the destruction motifs of Mad3 [61]. It has been recently shown that Cdc20 is ubiquitinated by APC/C when the spindle checkpoint is active [65, 66]. Interestingly, Mad3 is unstable in G1 whereas it is stable in nocodazole-treated cells [61]. These results suggest the intriguing possibility that Mad3 binding to Cdc20 directs APC/C activity towards Cdc20, perhaps by mimicking substrate binding. Cdc20 ubiquitination leads to its proteasome-dependent degradation, ensuring that Cdc20 levels are kept below a certain threshold to prevent unscheduled APC/C activation [67].. Two recent studies have shown that degradation of Cdc20 is not the only outcome of Cdc20 ubiquitination [65, 66]. Reddy et al. have shown that Cdc20 ubiquitination decreases its binding to Mad2 and to APC/C [66]. Cdc20 ...
Morgan, D.O. (2007) The Cell Cycle: Principles of Control. London: New Science Press.. Thornton, B.R., Ng, T.M., Matyskiela, M.E., Carroll, C.W., Morgan, D.O., and Toczyski, D.P. (2006) An architectural map of the anaphase-promoting complex. Genes Dev. 20, 449-460. Carroll, C.W., and Morgan, D.O. (2005) Enzymology of the Anaphase-Promoting Complex. Meth. Enzymol. 398, 219-230.. Loog, M., and Morgan, D.O. (2005) Cyclin specificity in the phosphorylation of cyclin-dependent kinase substrates. Nature 434, 104-108. (Commentary: Nature 434, 34-35; and Nat. Rev. Mol. Cell Biol. 6, 280). Carroll, C.W., Enquist-Newman, M., and Morgan, D.O. (2005) The APC subunit Doc1 promotes recognition of the substrate destruction box. Curr. Biol. 15, 11-18.. Ubersax, J.A., Woodbury, E.L., Quang, P.N., Paraz, M., Blethrow, J.D., Shah, K., Shokat, K.M., and Morgan, D.O. (2003) Targets of the cyclin-dependent kinase Cdk1. Nature, 425, 859-864.. Carroll, C.W., and Morgan, D.O. (2002) The Doc1 subunit is a processivity ...
The endocycle provides a useful model for determining the minimum cell cycle inputs required to achieve a G/S oscillation and the once-per-cell-cycle replication of the genome. Here, we demonstrate that APC/C activity is required for endocycle progression. During the endocycle, mitotic activities are repressed (reviewed by Edgar and Orr-Weaver, 2001; Lilly and Duronio, 2005). This is accomplished, at least in part, by preventing the accumulation of the mitotic activators Cyclin A, Cyclin B and Cdc25, which function to activate the mitotic kinase Cdk1. During the mitotic cycle, the mitotic cyclins are periodically targeted for regulated proteolysis by the E3-Ubiquintin ligase the APC/C (Dawson et al., 1995; Sigrist et al., 1995; Sigrist and Lehner, 1997). Yet the transcriptional downregulation of several APC/C targets at the mitotic/endocycle boundary, including the mitotic cyclins and String/Cdc25, suggested that the proteolytic activity of the APC/C might not be necessary during endocycles ...
The E3-ubiquitin ligase APC/C-Cdh1 is essential for endoreduplication but its relevance in the mammalian mitotic cell cycle is still unclear. Here we show that genetic ablation of Cdh1 in the developing nervous system results in hypoplastic brain and
There is an ever increasing amount of evidence for considering RASSF1A as a bona fide tumor suppressor gene ( 1). It remains, however, difficult to ascertain how RASSF1A can exert its tumor suppressive functions. Understanding the functions of the RASSF1A-interacting microtubule-associated protein C19ORF5 will yield greater understanding of the RASSF1A-regulated signaling pathways and ultimately will benefit our understanding of the multiple steps of carcinogenesis. Song et al. ( 18) suggested that C19ORF5 (or RABP1 as they refer to it in their article) is a centrosomal protein responsible for recruiting RASSF1A to the spindle poles where it can exert inhibitory actions on the activation of the anaphase-promoting complex/Cdc20 complex and block the prometaphase to metaphase progression. The authors have also reported that depletion of C19ORF5/RABP1 accelerates mitotic progression and increases the frequency of abnormal mitosis. We extended on these observations, but instead of using short ...
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Organ Nakli Merkezi, Tüp Bebek Merkezi, Havacılık Tıp Merkezi, Uyku bozuklukları Merkezi, Sigarayı bıraktırma merkezi, Poliklinik Hizmetleri ile 295 yataklı Başkent Üniversitesi Hastanesinde ve hastaneye bağlı, 90 yataklı Ayaş Fizik Tedavi ve Rehabilitasyon Merkezi ve 65 yataklı Yapracık Psiko-Sosyal Rehabilitasyon Merkezi gibi kuruluşları ile hizmetinizde..
Johnny Rotten once sang; blind acceptance is a sign, of stupid fools who stand in line like EMI. Yeah. He also sang And you thought that we were faking, ...
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transducin/WD-40 repeat-containing protein; Has a dual function in spindle-assembly checkpoint signaling and in promoting the establishment of correct kinetochore-microtubule (K-MT) attachments. Promotes the formation of stable end-on bipolar attachments. Necessary for kinetochore localization of BUB1. The BUB1/BUB3 complex plays a role in the inhibition of anaphase-promoting complex or cyclosome (APC/C) when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20 (By similarity) (314 aa ...
When the APC complex was inhibited by siRNA of APC3, the level of BubR1 remained constant for 60 min after nocodazole release in the presence of CHX, whereas it declined in control cells (Figure 8B). This result was corroborated by the finding from live‐cell assay for proteolysis that depleting APC3 expression abrogated the degradation of BubR1, and concomitantly cells did not enter anaphase for more than 5 h (Supplementary Figure 12 and Supplementary movie 7). When we compared the timing of BubR1 degradation with the degradation of other players in mitosis, such as Cdc20, Cyclin B, Plk1, and Aurora A, we found that BubR1 degradation began before that of Cyclin B (Supplementary Figure 13).. Next, we tested whether Cdc20 was responsible for BubR1 degradation during mitosis. To prevent the cells from exiting mitosis before the analysis began, HeLa cells were transfected with an expression construct to force moderate expression of Cyclin B. siRNA for GFP, Cdc20, or Cdh1 was simultaneously ...
During cell division, complex signalling pathways ensure that the two daughter cells separate only when each has received a single complete set of chromosomes. Carlos Vázquez de Aldana and co-workers describe how, at high temperatures, the protein Swm1p is needed for the final stages of cell separation in Saccharomyces cerevisiae (see p. 545). Swm1p is a core subunit in the anaphase-promoting complex (APC), the E3 ubiquitin ligase that initiates the metaphase-anaphase transition and promotes mitotic exit once chromosome segregation is complete. The authors report that, at 38°C, swm1 cells - mutants lacking SWM1 - form chains instead of separating into single cells after chromosome segregation. This behaviour results from reduced expression of chitinase and other proteins involved in separation, all of which require the transcription factor Ace2p for their expression. The authors show that at 38°C Ace2p fails to move from the cytoplasm to the nucleus (as happens at 28°C) at the end of ...
Overexpression of mitotic cyclin CLB2 results in premature spindle elongation in swe1Δ mutants.A. Overexpression of CLB2 is toxic to swe1Δ mutants. WT and swe
APCcdh1 Mediates Degradation of the Oncogenic Rho-GEF Ect2 after Mitosis. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
The Author. In a world of informational overload, an informational guide is only as good as its author. As such, it is a worthwhile endeavor to help you understand the brain behind this particular guide.. Diseaseless is a product of Ken Drew. Kens background was punctuated with illnesses of all manner, from simple colds and flu to more serious diseases.. By the time he was 40, Kens appearance resembled that of a 60 year old man. Due to constant illness, Ken wasnt able to look after his family because he couldnt work.. Ken decided that enough was enough and he decided to take matters of his health in his own hands. Through some grueling research and hundreds of trials, he finally came up with a series of treatment options that could not only clear many illnesses but also prevent them.. Ken decided to compile these treatment options into one digital guide called Diseaseless. Everything in the guide has been used and tested by him. He managed to revitalize his health and rid his body of all ...
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On the evening of October 14, 2017, Lesley Rebeca Parrott passed away surrounded by family. She was born January 9, 1989, in Kent, WA to Craig and Anna (Wright) Parrott.
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The ubiquitin-proteasome system is a post-translational regulatory pathway for controlling protein stability and activity that underlies many fundamental cellular processes, including cell cycle progression. Target proteins are tagged with ubiquitin molecules through the action of an enzymatic cascade composed of E1 ubiquitin activating enzymes, E2 ubiquitin conjugating enzymes, and E3 ubiquitin ligases. One of the E3 ligases known to be responsible for the ubiquitination of cell cycle regulators in eukaryotes is the SKP1-CUL1-F-box complex (SCFC). In this work, we identified and studied the function of homologue proteins of the SCFC in the life cycle of Trypanosoma brucei, the causal agent of the African sleeping sickness. Depletion of trypanosomal SCFC components TbRBX1, TbSKP1, and TbCDC34 by RNAi resulted in decreased growth rate and contrasting cell cycle abnormalities for both procyclic (PCF) and bloodstream (BSF) forms. Depletion of TbRBX1 in PCF cells interfered with kinetoplast ...
FZR1 (fizzy-related protein homolog; also known as CDH1 [cell division cycle 20 related 1]) functions in the cell cycle as a specific activator of anaphase-promoting complex or cyclosome ubiquitin ligase, regulating late mitosis, G1 phase, and activation of the G2-M checkpoint. FZR1 has been implicated as both a tumor suppressor and oncoprotein, and its precise contribution to carcinogenesis remains unclear. Here, we examined the role of FZR1 in tumorigenesis and cancer therapy by analyzing tumor models and patient specimens. In an Fzr1 gene-trap mouse model of B-cell acute lymphoblastic leukemia (B-ALL), mice with Fzr1-deficient B-ALL survived longer than those with Fzr1-intact disease, and sensitivity of Fzr1-deficient B-ALL cells to DNA damage appeared increased. Consistently, conditional knockdown of FZR1 sensitized human B-ALL cell lines to DNA damage-induced cell death. Moreover, multivariate analyses of reverse-phase protein array of B-ALL specimens from newly diagnosed B-ALL patients ...
Abiotic stresses, such as drought, have long been known to inhibit plant growth and thereby decrease crop productivity. This growth inhibition is an active response to stress, but little is currently known on how this is brought about (Skirycz and Inzé, 2010). Recently, it has become evident that tolerance to stress, which has been extensively studied in the past, relies on different mechanisms than growth inhibition by stress and that specific experimental setups have to be developed to investigate stress-induced growth inhibition (Skirycz et al., 2011b).. Organ growth is driven by both cell proliferation and cell expansion, in the case of Arabidopsis (Arabidopsis thaliana) leaf growth occurring sequentially in time. Initially, all cells in the leaf primordium are dividing, but later in development, cell division ceases from the tip to the base of the leaf, resulting in a cell cycle arrest front moving across the leaf (Donnelly et al., 1999; Kazama et al., 2010; Andriankaja et al., 2012). This ...
S. Mosalaganti, J. Keller, A. Altenfeld, M. Winzker, P. Rombaut, M. Saur, A. Petrovic, A. Wehenkel, S. Wohlgemuth, F. Müller, S. Maffini, T. Bange, F. Herzog, H. Waldmann, S. Raunser, A. Musacchio: Structure of the RZZ complex and molecular basis of its interaction with Spindly. J Cell Biol. 2017, 216:961-981.. A. C. Faesen, M. Thanasoula, S. Maffini, C. Breit, F. Müller, S. van Gerwen, T. Bange, A. Musacchio: Basis of catalytic assembly of the mitotic checkpoint complex. Nature. 2017, 542:498-502.. D. Pan, K. Klare, A. Petrovic, A. Take, K. Walstein, P. Singh, A. Rondelet, A.W. Bird, A. Musacchio: CDK-regulated dimerization of M18BP1 on a Mis18 hexamer is necessary for CENP-A loading. Elife. 2017 6. pii: e23352.. A. Petrovic, J. Keller, Y. Liu, K. Overlack, J. John, Y. Dimitrova, S. Jenni, S. van Gerwen, P. Stege, S. Wohlgemuth, P. Rombaut, F. Herzog, S.C. Harrison, I. Vetter, A. Musacchio: Structure of the MIS12 complex and molecular basis of its interaction with CENP-C at human ...
Tom Kucharski from the Teodoro Lab presented a talk at the recent cell cycle meeting at Cold Spring Harbor Laboratory entitled: 53BP1 is a novel anaphase promoting complex/cyclosome mitotic substrate and regulator
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KENT CITY, Michigan. -- Emergency crews responded to a minor ammonia leak on a farm Tuesday at 3509 18-Mile road in Kent City. According to the Kent County Sheriffs department the leak was reported shortly before 10:30 in the morning.
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Afters months of waiting, I have finally been able to get my act together enough to post the answers to questions you posed to |a href=http://www.science.oregonstate.edu/~kentad/|Dr. Adam Kent|/a|. If you remember back to |a href=http://bigthink.com/ideas/24029|the beginning of the fall|/a|, Dr. Kent and his colleagues published a paper in |em|Nature Geosciences|/em| about the |a href=http://www.nature.com/ngeo/journal/v3/n9/abs/ngeo924.html|nature of magma mixing|/a| and ...
Before you buy Ken Paves You Are Beautiful Repair & Nourish Shine Serum, check out 4 Influenster reviews. Vivianna H. said Is this a good product? What are...
Visit Healthgrades for information on Dr. Kent Lerner, MD Find Phone & Address information, medical practice history, affiliated hospitals and more.
Visit Healthgrades for information on Dr. Ken Danylchuk, MD Find Phone & Address information, medical practice history, affiliated hospitals and more.
So Ken Ham wont debate Aron Ra and PZ Myers because... reasons! He complained that the debate invitation was rude, but look how rude he was to Bill Nye...
The Anaphase-Promoting Complex (APC) is a multi-subunit E3 ubiquitin ligase that coordinates progression through the cell cycle by temporally and spatially promoting the degradation of key proteins. Many of these targeted proteins have been shown to play important roles in regulating orderly progression through the cell cycle. Using a previously described Drosophila in vitro expression cloning approach, we screened for new substrates of the APC in Xenopus egg extract and identified Drosophila MCPH1 (dMCPH1), a protein encoded by the homolog of a causative gene for autosomal recessive primary microcephaly in humans. The dMCPH1-B splice form, but not the dMCPH1-C splice form, undergoes robust degradation in Xenopus interphase egg extract in a Cdh1-dependent manner. Degradation of dMCPH1-B is controlled by an N-terminal destruction box (D-box) motif as its deletion or mutation blocks dMCPH1-B degradation. dMCPH1 levels are increased in Drosophila morula (APC2) mutant embryos, consistent with dMCPH1 ...
The Kent Tribune. i - LOCAL LEADER IN BOTH NEWS AND CIRCULATION. War Savings Stamps are a Wise Investment. Early Christmas Shopping Helps Everybody. VOLUME III. NO. 50 KENT, OHIO, THURSDAY MORNING, OCT. 24, 1918 5c A COPY, $1.50 A YEAR Taught Thirty Successive Years. Death, of Mrs. Adda Garrison, Beloved and Successful Instructor in the Kent Schools. MRS. ADDA GARRISON. Mrs. Adda Garrison, who had devoted the greater part of her life- to the training of young lives, her work reaching to the children of her early pupils, passed away at 8 oclock Monday evening. Mrs. Garrison was a teacher greatly loved for her kindness and painstaking work, not only by her pupils but also by their parents and friends. She possessed the traits that enabled her to get the best results with corresponding benefits . to . the pupils, Discipline was easy for her. Her pupils loved her and took a real in terest in the work under her devotion and guidance. For thirty consecutive years she taught in. the schools of Kent. ...
... Ken was a chef before a motorbike crash turned his life upside down Ken was a chef before a motorbike crash turned his life upside down in 2001.Ken suffered horrific injuries, including muscle spasticity. It stopped my chefing career and I was lost because Id
Function Description Abs1D Finds the absolute values of the array elements. Add1D Adds two 1D arrays, element by element. Add2D Adds two 2D arrays, element by element. AllocCxIIRFilterStatePtr Allocates and initializes the filterInformation structure. AllocIIRFilterPtr Allocates and initializes the
KENT, Ohio (AP) Justin Greene scored 18 points and grabbed nine rebounds to lead Kent State to an easy 76-55 win over Ball State on Saturday.
Cellular reproduction: Mitosis 16 cell-cycle regulators are essential. If one is missing, the cell-cycle is not completed. Therefore, the regulation of the cell
Here is the best resource for homework help with BSCI 10120 : BIOLOGICAL FOUNDATIONS at Kent State. Find BSCI10120 study guides, notes, and practice tests
With a ton of new cast members being introduced in the final season of Glee, its no surprise that theres also going to be some amazing guest stars -- and that includes Jennifer Coolidge and Ken Jeong, and HollywoodLife.com can exclusively tell you when youll see them.
RHs Kent Powder Vanity:We've embraced the individualistic possibilities of classical style, offering our timeless collection with your choice of paint colors and vanity tops.
Inside Singapore: Kent Ridge Park - Before you visit Singapore, visit TripAdvisor for the latest info and advice, written for travelers by travelers.
Brendon W. Kent is the author of this article in the Journal of Visualized Experiments: Zemin Projeksiyon Maze kullanma Kayıt Sinir Aktivitesi otomatik Görsel Bilişsel Görevler
You see, Kent was fighting a Stage 4 cancer and it had been a pretty rough fight for him. Each update told of a body that was getting weaker yet a soul that was still burning brightly and fighting for all it was worth. Neither of them ever complained about anything and Melony spoke of Kent with so much love that you could actually feel it yourself. Kent showed his love by fighting and refusing to leave his family. All this and more is why they will eternally be my heroes. ...
J:58906 Kandli M, et al., Isolation and characterization of two evolutionarily conserved murine kinases (Nek6 and nek7) related to the fungal mitotic regulator, NIMA. Genomics. 2000 Sep 1;68(2):187-96 ...
Anyway, to fill comment readers in, Nando Pelusi is a Rational Emotive Therapist who I first saw performing in the playlet Mozart Was A Red -- or maybe that was the 2nd time I saw him -- and years later, I heard a rerun of a 7SD in which he did relationship counseling of Andy & Ken, when Nandos office was in NJ. Hes in Manhattan now ...
The spindle checkpoint is a key mechanism that ensures accurate distribution of the chromosomes during cell division by delaying completion of mitosis until kinetochores of the chromosomes are attached to spindle microtubules and until tension is being applied to pull the sister kinetochores toward opposite spindle poles. Why, then, once anaphase begins and the sister chromatids begin to separate, is the checkpoint not reactivated? Palframan et al. describe a feedback loop of mutual inhibition between the APC (anaphase-promoting complex, a ubiquitin E3 ligase complex that targets proteins for degradation) and Mps1 (a protein kinase that is part of the checkpoint signaling pathway). Once the checkpoint conditions are satisfied and anaphase begins, the inhibition of APC by Mps appears to dip below a critical threshold. At this point, the APC apparently switches to an "on" state in which anaphase is promoted and Mps1 (which is itself a target of the APC) is degraded and can thus no longer activate ...
Prophase I arrest, referred to as the germinal vesicle (GV) stage, is a conserved feature of oocytes across species (Whitaker, 1996; Mehlmann, 2005; Jones, 2008). In mice, as in all mammals, GV arrest begins shortly after meiotic recombination in fetal life. Periodic, non-hormonal recruitment of a small number of quiescent follicles into the growing pool after birth leads to follicle growth and eventual ovulation, both of which are hormone dependent. It is only near the time of ovulation in the fully grown oocytes of mature follicles that a rise in luteinizing hormone (LH) breaks this arrest, causing GV breakdown (GVB).. A high level of cAMP, generated from a Gs-coupled oocyte receptor, is needed to maintain arrest in fully grown oocytes (Cho et al., 1974; Magnusson and Hillensjo, 1977; Bornslaeger et al., 1986; Mehlmann et al., 2002; Freudzon et al., 2005). This is enhanced by cGMP from the surrounding cumulus cells, which inhibits phosphodiesterase 3A (PDE3A) activity, preventing cAMP ...
Chromosome segregation and cell division are essential, highly ordered processes that depend on numerous protein complexes. Results from recent RNA interference screens indicate that the identity and composition of these protein complexes is incompletely understood. Using gene tagging on bacterial artificial chromosomes, protein localization, and tandem-affinity purification-mass spectrometry, the MitoCheck consortium has analyzed about 100 human protein complexes, many of which had not or had only incompletely been characterized. This work has led to the discovery of previously unknown, evolutionarily conserved subunits of the anaphase-promoting complex and the gamma-tubulin ring complex--large complexes that are essential for spindle assembly and chromosome segregation. The approaches we describe here are generally applicable to high-throughput follow-up analyses of phenotypic screens in mammalian cells ...
Cell prolifertion is a fundamental aspect of live. Cells reproduce by a series of coordinated events that is called the cell cycle. Our research goal is to understand the basic control of the cell cycle and its coordination within a multicellular organism. We use yeast (Saccharomyces cerevisiae) and the fruit fly (Drosophila) as model systems. Major projects focus on exit from mitosis, the regulation of the Ubiquitin Ligase APC/C (Anaphase-Promoting-Complex/Cyclosome) and control of special cell cycles during development. ...
Find info concerning Kent OH nursing program. Healthcare is one of the fastest-growing job areas, and for good reason. As the population ages, medical facilities will continue to expand rapidly.
144 MINNIS ROAD BIRCHINGTON (MANAGEMENT) LIMITED KENT - Directors MARIE JENNINGS and 3 others. Official financial information, directors details and trading history.
Sreymom Ken is currentky working in Infectious Disease Institute, Makerere University, Kampala, Uganda .Publications involved are HIV-1 Protease Inhibitors Resis..
Background: The spindle checkpoint ensures accurate chromosome transmission by delaying chromosome segregation until all chromosomes are correctly aligned on the mitotic spindle. The checkpoint is activated by kinetochores that are not attached to microtubules or are attached but not under tension and arrests cells at metaphase by inhibiting the anaphase-promoting complex (APC) and its coactivator Cdc20. Despite numerous studies, we still do not understand how the checkpoint proteins coordinate with each other to inhibit \(APC^{Cdc20}\) activity. Results: To ask how the checkpoint components induce metaphase arrest, we constructed fusions of checkpoint proteins and expressed them in the budding yeast Saccharomyces cerevisiae to mimic possible protein interactions during checkpoint activation. We found that expression of a Mad2-Mad3 protein fusion or noncovalently linked Mad2 and Mad3, but not the overexpression of the two separate proteins, induces metaphase arrest that is independent of ...

Differential Regulation of Anaphase Promoting Complex/Cyclosome Substrates by the Spindle Assembly Checkpoint in Saccharomyces...Differential Regulation of Anaphase Promoting Complex/Cyclosome Substrates by the Spindle Assembly Checkpoint in Saccharomyces...

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 ...
more infohttp://www.genetics.org/content/178/1/589

Polo-Like Kinase 1: Target and Regulator of Anaphase-Promoting Complex/Cyclosome-Dependent Proteolysis | Cancer ResearchPolo-Like Kinase 1: Target and Regulator of Anaphase-Promoting Complex/Cyclosome-Dependent Proteolysis | Cancer Research

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 ...
more infohttp://cancerres.aacrjournals.org/content/66/14/6895

APC16 is a conserved subunit of the anaphase-promoting complex/cyclosome | Journal of Cell ScienceAPC16 is a conserved subunit of the anaphase-promoting complex/cyclosome | Journal of Cell Science

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 ...
more infohttp://jcs.biologists.org/content/123/10/1623.full

DELLA Signaling Mediates Stress-Induced Cell Differentiation in Arabidopsis Leaves through Modulation of Anaphase-Promoting...DELLA Signaling Mediates Stress-Induced Cell Differentiation in Arabidopsis Leaves through Modulation of Anaphase-Promoting...

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 ...
more infohttp://www.plantphysiol.org/content/159/2/739.full.print

DELLA Signaling Mediates Stress-Induced Cell Differentiation in Arabidopsis Leaves through Modulation of Anaphase-Promoting...DELLA Signaling Mediates Stress-Induced Cell Differentiation in Arabidopsis Leaves through Modulation of Anaphase-Promoting...

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 ...
more infohttp://www.plantphysiol.org/content/159/2/739.full

Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis | BMC...Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis | BMC...

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 ...
more infohttps://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-12-44

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...

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 ...
more infohttps://bio.as.uky.edu/bimaapc3-component-aspergillus-anaphase-promoting-complexcyclosome-required-g2-checkpoint-blocking

Transcriptional intermediary factor 1γ binds to the anaphase-promoting complex/cyclosome and promotes mitosis - Danish National...Transcriptional intermediary factor 1γ binds to the anaphase-promoting complex/cyclosome and promotes mitosis - Danish National...

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 ...
more infohttps://www.forskningsdatabasen.dk/en/catalog/232925734

Role of Polo-like kinase in the degradation of early mitotic inhibitor 1, a regulator of the anaphase promoting complex...Role of Polo-like kinase in the degradation of early mitotic inhibitor 1, a regulator of the anaphase promoting complex...

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- ...
more infohttp://www.pnas.org/content/101/21/7937

Anaphase-promoting complex subunit 1 (IPR024990) | InterPro | EMBL-EBIAnaphase-promoting complex subunit 1 (IPR024990) | InterPro | EMBL-EBI

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 ...
more infohttp://www.ebi.ac.uk/interpro/entry/IPR024990

Identification of a physiological E2 module for the human anaphase-promoting complex | PNASIdentification of a physiological E2 module for the human anaphase-promoting complex | PNAS

2006) The anaphase-promoting complex/cyclosome: A machine designed to destroy. Nat Rev Mol Cell Biol 7:644-656. ... 2001) Anaphase-promoting complex/cyclosome-dependent proteolysis of human cyclin A starts at the beginning of mitosis and is ... 2007) The END network couples spindle pole assembly to inhibition of the anaphase-promoting complex/cyclosome in early mitosis ... 2004) Degradation of the SCF component Skp2 in cell-cycle phase G1 by the anaphase-promoting complex. Nature 428:194-198. ...
more infohttps://www.pnas.org/content/106/43/18213?ijkey=6803e6fc346ade32dd2daf90d473ddccb641d948&keytype2=tf_ipsecsha

Structural Biochemistry/Enzyme Regulation/Ubiquitination - Wikibooks, open books for an open worldStructural Biochemistry/Enzyme Regulation/Ubiquitination - Wikibooks, open books for an open world

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 ( ...
more infohttps://en.wikibooks.org/wiki/Structural_Biochemistry/Enzyme_Regulation/Ubiquitination

Binding Partner Switching on Microtubules and Aurora-B in the Mitosis to Cytokinesis Transition | Molecular & Cellular...Binding Partner Switching on Microtubules and Aurora-B in the Mitosis to Cytokinesis Transition | Molecular & Cellular...

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, ...
more infohttps://www.mcponline.org/content/9/2/336?ijkey=a31bb8025632ef022e58eafeb505b0157b16c481&keytype2=tf_ipsecsha

Prostate-specific membrane antigen associates with anaphase-promoting complex and induces chromosomal instability | Molecular...Prostate-specific membrane antigen associates with anaphase-promoting complex and induces chromosomal instability | Molecular...

The anaphase promoting complex/cyclosome: a machine designed to destroy. Nat Rev Mol Cell Biol 2006;7:644-56. ... Herzog F, Peters J. Large-scale purification of the vertebrate anaphase-promoting complex/cyclosome. In: Deshaies RJ, editor. ... Inhibition of the anaphase-promoting complex by the Xnf7 ubiquitin ligase. J Cell Biol 2005;169:61-71. ... Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex. Cell 2001;105:645-55. ...
more infohttp://mct.aacrjournals.org/content/7/7/2142

Control of the pericentrosomal H2O2 level by peroxiredoxin I is critical for mitotic progression | JCBControl of the pericentrosomal H2O2 level by peroxiredoxin I is critical for mitotic progression | JCB

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 ...
more infohttp://jcb.rupress.org/content/210/1/23

Frontiers | Multiple Duties for Spindle Assembly Checkpoint Kinases in Meiosis | Cell and Developmental BiologyFrontiers | Multiple Duties for Spindle Assembly Checkpoint Kinases in Meiosis | Cell and Developmental Biology

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 ...
more infohttps://www.frontiersin.org/articles/10.3389/fcell.2017.00109/full

A Bub1-Mad1 interaction targets the Mad1-Mad2 complex to unattached kinetochores to initiate the spindle checkpoint | JCBA Bub1-Mad1 interaction targets the Mad1-Mad2 complex to unattached kinetochores to initiate the spindle checkpoint | JCB

The spindle checkpoint generates a "wait anaphase" signal that inhibits the anaphase-promoting complex/cyclosome (APC/C; ... anaphase-promoting complex/cyclosome. dsRNA. double-stranded RNA. FL. full length. MBP. maltose-binding protein. mCh. mCherry. ... S2 G). MAD-1 meiosis I anaphase localization required BUB-1 but not the NDC-80 or RZZ complexes, which are required for MAD-1 ... revealed that MAD-1-MAD-2 kinetochore targeting requires the Ndc80 complex, the RZZ complex, and BUB-1 (Fig. 1 A; Gassmann et ...
more infohttp://jcb.rupress.org/content/204/5/647

KAKEN - Research Projects | SUMOylation is involved in the regulation of cell cycle check point (KAKENHI-PROJECT-25440134)KAKEN - Research Projects | SUMOylation is involved in the regulation of cell cycle check point (KAKENHI-PROJECT-25440134)

Presentation] The Anaphase-Promoting Complex/ Cyclosome Regulates Microtubule Structures through the Cell Cycle2014. *. Author( ...
more infohttps://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-25440134/

SWISS-MODEL Template Library | 4yii.1SWISS-MODEL Template Library | 4yii.1

Structure of an APC2-UBCH10 complex reveals distinctive cullin-RING ligase mechanism for Anaphase-promoting complex/Cyclosome ... Structure of an APC2-UBCH10 complex reveals distinctive cullin-RING ligase mechanism for Anaphase-promoting complex/Cyclosome. ... Brown, N.G. et al., Crystal Structure of E2 Complex. Proc.Natl.Acad.Sci.USA (2015) Release Date. 2015-04-08. Peptides. ...
more infohttps://swissmodel.expasy.org/templates/4yii

BRK1, a Bub1-Related Kinase, Is Essential for Generating Proper Tension between Homologous Kinetochores at Metaphase I of Rice...BRK1, a Bub1-Related Kinase, Is Essential for Generating Proper Tension between Homologous Kinetochores at Metaphase I of Rice...

anaphase-promoting complex/cyclosome. CPC. chromosomal passenger complex. RACE. rapid amplification of cDNA ends. RNAi. RNA ... 2007). KEN-box-dependent degradation of the Bub1 spindle checkpoint kinase by the anaphase-promoting complex/cyclosome. J. Biol ... these proteins collaborate to inhibit the ubiquitin ligase activity of the anaphase-promoting complex/cyclosome (APC/C), ... 2002). The anaphase-promoting complex: Proteolysis in mitosis and beyond. Mol. Cell 9: 931-943. ...
more infohttp://www.plantcell.org/content/24/12/4961.full

Mps1 directs the assembly of Cdc20 inhibitory complexes during interphase and mitosis to control M phase timing and spindle...Mps1 directs the assembly of Cdc20 inhibitory complexes during interphase and mitosis to control M phase timing and spindle...

Structure of the anaphase-promoting complex/cyclosome interacting with a mitotic checkpoint complex. Science. 323:1477-1481 ... The anaphase promoting complex/cyclosome: a machine designed to destroy. Nat. Rev. Mol. Cell Biol. 7:644-656 10.1038/nrm1988 [ ... anaphase-promoting complex/cyclosome. CENP. centromere protein. hTERT. human telomerase reverse transcriptase. IP. ... the SAC acts by inhibiting the Cdc20-bound form of the anaphase-promoting complex/cyclosome (APC/C), a large ubiquitin protein ...
more infohttp://pubmedcentralcanada.ca/pmcc/articles/PMC2911671/

Protein Purification Technique that Allows Detection of Sumoylation and Ubiquitination of Budding Yeast Kinetochore Proteins...Protein Purification Technique that Allows Detection of Sumoylation and Ubiquitination of Budding Yeast Kinetochore Proteins...

Li, L., et al. Anaphase-promoting complex/cyclosome controls HEC1 stability. Cell Prolif. 44, 1-9 (2011). ... Akiyoshi, B., et al. The Mub1/Ubr2 ubiquitin ligase complex regulates the conserved Dsn1 kinetochore protein. PLoS Genet. 9, ... Tandem Affinity Purification of Protein Complexes from Eukaryotic Cells…. Published 1/26/2017 ... which phosphorylates Dam1 and Ndc80 complexes that directly interact with microtubules 6-8. Despite the identification of over ...
more infohttps://www.jove.com/video/52482/protein-purification-technique-that-allows-detection-sumoylation

Targetting Cdks in Cancer: An Overview and New Insights | OMICS InternationalTargetting Cdks in Cancer: An Overview and New Insights | OMICS International

Clarke DJ,Díaz-Martínez LA, Giménez-Abián JF (2005) Anaphase promoting complex or cyclosome? Cell Cycle 4: 1585-1592. ... Anaphase Promoting Complex/Cyclosome; CDKL: CDK Like; CDC2L: CDC2 Like Kinase; CCRK: Cell Cycle Related Kinase; MPF: Maturation ... or anaphasepromoting complex/cyclosome (APC/C) and subsequent degradation within the proteasome [3]. The individual gene ... CDK1, in complex with A or B type cyclins, is one of the master regulators of mitosis. The loss of fuction of CDK1 has been ...
more infohttps://www.omicsonline.org/open-access/targetting-cdks-in-cancer-an-overview-and-new-insights-1948-5956.1000313.php?aid=36618

Dynamical behavior of APC:Cdc20 concentration versus ti | Open-iDynamical behavior of APC:Cdc20 concentration versus ti | Open-i

Anaphase-Promoting Complex-Cyclosome. *Calcium-Binding Proteins/physiology. *Cdc20 Proteins. *Cell Cycle Proteins/metabolism/ ... Conclusion: Only in the controlled case, our models show (M)SAC behaviour at meta- to anaphase transition in agreement with ... Conclusion: Only in the controlled case, our models show (M)SAC behaviour at meta- to anaphase transition in agreement with ... Cdc20 complex. MCC:APC dissociation is described by two alternatives, namely the "Dissociation" and the "Convey" model variants ...
more infohttps://openi.nlm.nih.gov/detailedresult.php?img=PMC2215771_pone.0001555.g002&req=4

Stefanie PolynStefanie Polyn

Tissue-specific control of the endocycle by the anaphase promoting complex/cyclosome inhibitors UVI4 and DEL1 Jefri Heyman ( ...
more infohttps://biblio.ugent.be/person/000080267597
  • 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)
  • 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)
  • 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)
  • E3s containing a RING-domain recruit substrates and ubiquitin-charged E2s, and promote the transfer of ubiquitin from the E2 active site to a substrate lysine. (pnas.org)
  • 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)
  • Cdh1 comprises different domains important for its proper function, when it interacts with the APC/c complex and the various substrates. (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 have constructed and validated for the human (M)SAC mechanism an in silico dynamical model, integrating 11 proteins and complexes. (nih.gov)
  • 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)
  • 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)
  • The myeloma drug lenalidomide promotes the cereblon-dependent destruction of ikaros proteins. (nature.com)
  • Eukaryotic cells replicate by a complex series of evolutionarily conserved events that are tightly regulated at defined stages of the cell division cycle. (sciencemag.org)
  • Because APC/C not only ensures cell cycle arrest upon spindle disruption but also promotes cell death in response to prolonged mitotic arrest, it has become an attractive drug target in cancer therapy. (biomedcentral.com)
  • 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)