• This event is required to promote mitotic progression and favors the activation of a transcriptional program required for mitosis. (ox.ac.uk)
  • A study in 2008 provided further evidence of cyclin A/CDK2 complex's role in mitosis. (wikipedia.org)
  • These mutants entered mitosis late due to a delayed activation of the cyclin B/CDK1 complex. (wikipedia.org)
  • We introduced autocatalytic transcription of E2F, E2F regulated transcription of cyclin B, Cdc20/Cdh1 mediated E2F degradation, enhanced transcription of mitotic cyclins during late S/early G2 phase, and the sustained synthesis of cyclin B during mitosis. (ebi.ac.uk)
  • The role of BubR1 has been established mainly in mitosis as an essential mitotic checkpoint protein although it is expressed throughout the cell cycle. (ewha.ac.kr)
  • This degradation process is ubiquitin-dependent and is necessary for the cell to exit mitosis. (nsjbio.com)
  • The CDK4 activity associated with this cyclin was reported to be necessary for cell cycle progression through G2 phase into mitosis after UV radiation. (creative-biolabs.com)
  • An aurora kinase that localizes to the CENTROSOME during MITOSIS and is involved in centrosome regulation and formation of the MITOTIC SPINDLE. (lookformedical.com)
  • B-type cyclins are rapidly degraded in the transition between metaphase and anaphase and their ubiquitin-mediated proteolysis is necessary for cells to exit mitosis. (bibf1120.com)
  • Exposure of the cells to gemcitabine at G2/M transition abolished the progression of mitosis, caused mitotic arrest and failure to exit mitosis as evidenced by the inhibition of Cyclin B degradation and absence of de-phosphorylation of cdc-2 at Tyr 15 residue. (bmj.com)
  • Here, we used experimental and computational approaches to dissect the quantitative mechanisms underlying the ordered degradation of the substrates of the ubiquitin ligase APC/C Cdc20 , a key regulator of chromosome segregation in mitosis. (biomedcentral.com)
  • The activator Cdc20 is then replaced by a second activator, Cdh1, and APC/C Cdh1 promotes complete degradation of M cyclin, followed by polo-like kinase 1, Aurora A, and other substrates, to complete mitosis and cytokinesis and drive progression into G1 [ 1 , 2 ]. (biomedcentral.com)
  • Mitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. (kegg.jp)
  • The model pertains to the situation encountered in early amphibian embryos, where the accumulation of cyclin suffices to trigger the onset of mitosis. (physiomeproject.org)
  • Cyclin A can regulate multiple cell cycle steps because it associates with, and thereby activates, two distinct CDKs - CDK2 and CDK1. (wikipedia.org)
  • Association of cyclin A with CDK2 is required for passage into S phase while association with CDK1 is required for entry into M phase. (wikipedia.org)
  • In late S phase, cyclin A can also associate with CDK1. (wikipedia.org)
  • Cyclin A remains associated with CDK1 from late S into late G2 phase when it is replaced by cyclin B. Cyclin A/CDK1 is thought to be involved in the activation and stabilization of cyclin B/CDK1 complex. (wikipedia.org)
  • Degradation of cyclin A/CDK1 induces mitotic exit. (wikipedia.org)
  • It is suspected that the presence of cyclin A/CDK2 at the centrosomes may confer a means of regulating the movement of cyclin B/CDK1 to the centrosome and thus the timing of mitotic events. (wikipedia.org)
  • Cyclin A degradation employs preferentially used lysines and a cyclin box function other than Cdk1 binding. (nih.gov)
  • The model was built by integrating and modifying two previously published models such that the model outputs for cyclins A and B fit cyclin expression measurements and the activation of B cyclin/Cdk1 coincided with phosphorylation of histone H3. (ebi.ac.uk)
  • The model depends on Cdh1-regulated cyclin degradation during G1, regulation of B cyclin/Cdk1 activity by cyclin A/Cdk via Wee1, and transcriptional control of the mitotic cyclins that reflects some of the current literature. (ebi.ac.uk)
  • This is in contrast to control cells where cyclin B 1 appears at the centrosomes in early prophase based on cell cycle-specific localization of CENP-F. Furthermore, cyclin B/Cdk1 kinase activity in early G 2 is aberrantly high in BubR1-depleted cells. (ewha.ac.kr)
  • The model starts at mitotic entry initiated by the activities of Cyclin-dependent kinase 1 (CDK1) and Polo-like kinase 1 (PLK1), transitions through Anaphase-promoting complex (APC/C) bound to Cell division cycle protein 20 (CDC20), and ends upon mitotic exit mediated by APC/C bound to CDC20 homolog 1 (CDH1). (pharmafocusasia.com)
  • The precise regulation of the levels of cyclin proteins is fundamental to coordinate cell division with checkpoints, avoiding genome instability. (ox.ac.uk)
  • Cyclin A is a member of the cyclin family, a group of proteins that function in regulating progression through the cell cycle. (wikipedia.org)
  • The mechanism, which is based on the synthesis and degradation of three ''master regulator'' proteins (CtrA, GcrA, and DnaA), is converted into a quantitative model, in order to study the temporal dynamics of these and other cell cycle proteins. (ebi.ac.uk)
  • The activity of CDKs is controlled by their binding to coactivator subunits termed Cyclins, as well as by CDK inhibitory proteins termed CKIs. (intechopen.com)
  • The accumulation of both Cyclin and CKI proteins is tightly regulated at the level of transcription. (intechopen.com)
  • In addition, Cyclin and CKI proteins are controlled at the level of their destruction. (intechopen.com)
  • This phenotype is associated with interaction of E2 with the Mitotic Checkpoint Complex (MCC) proteins Cdc20, MAD2 and BUBR1. (docksci.com)
  • The APC/C is an E3 ubiquitin ligase that drives mitotic progression by promoting timely degradation of key regulatory proteins [ 3 ]. (biomedcentral.com)
  • It includes syntheses and multiple mechanisms of degradations of the mitotic proteins. (pharmafocusasia.com)
  • Recent breakthroughs have uncovered more and more DNA replication licensing machinery proteins (ORC, Cdc6, Cdt1, geminin, etc.) functioning in other cell cycle events, including centrosome replication, mitotic events, transcription and so on. (intechopen.com)
  • The degradation of cyclin F mediated by β-TrCP occurs at the G2/M transition. (ox.ac.uk)
  • Depending on which CDK partner cyclin A binds, the cell will continue through the S phase or it will transition from G2 to the M phase. (wikipedia.org)
  • Cyclin A has been shown to play a crucial role in the G2/M transition in Drosophila and Xenopus embryos. (wikipedia.org)
  • Initiation of transcription of cyclin A is coordinated with passage of the R point, a critical transition point that is required for progression from G1 into S phase. (wikipedia.org)
  • This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. (genetex.com)
  • In particular, ubiquitin-mediated degradation is critically important at transition points where it provides directionality and irreversibility to the cell cycle, which is essential for maintaining genome integrity. (intechopen.com)
  • This mitotic kinase complex remains active until the metaphase/anaphase transition when Cyclin B1 is degraded. (nsjbio.com)
  • Cyclin B1-p34cdc2 plays a critical role in G2 to M transition. (nsjbio.com)
  • Destruction of the CDC28/CLB mitotic kinase is not required for the metaphase to anaphase transition in budding yeast. (ox.ac.uk)
  • It is widely assumed that degradation of mitotic cyclins causes a decrease in mitotic cdc2/CDC28 kinase activity and thereby triggers the metaphase to anaphase transition. (ox.ac.uk)
  • The activity of NEK6 plays important roles in mitotic spindle kinetochore fiber formation, metaphase-anaphase transition, cytokinesis, and checkpoint regulation [ 3 , 4 ]. (hindawi.com)
  • β-TrCP- and Casein Kinase II-Mediated Degradation of Cyclin F Controls Timely Mitotic Progression. (ox.ac.uk)
  • Cyclin A, along with the other members of the cyclin family, regulates cell cycle progression through physically interacting with cyclin-dependent kinases (CDKs), which thereby activates the enzymatic activity of its CDK partner. (wikipedia.org)
  • Cyclin A/CDK2 complex was thought to be restricted to the nucleus and thus exclusively involved in S phase progression. (wikipedia.org)
  • Transcription of cyclin A is tightly regulated and synchronized with cell cycle progression. (wikipedia.org)
  • Progression through the cell cycle is driven by the oscillating activity of Cyclin Dependent Kinases (CDKs). (intechopen.com)
  • Paradoxically, progression deeper into cell cycle arrest was accompanied by increases in proliferative effectors such as CDKs and cyclins, which can drive cell cycle re-entry by overcoming p21 induction. (bvsalud.org)
  • Recent studies have shown that cyclin-dependent kinase (CDK) inhibitors can have a tremendous impact on cell cycle progression in plants. (uni-bielefeld.de)
  • Cyclins function as regulators of CDK kinases. (novusbio.com)
  • Mammalian aurora-A belongs to a multigenic family of mitotic serine/threonine kinases comprising two other members: aurora-B and aurora-C. In this review we will focus on aurora-A that starts to localize to centrosomes only in S phase as soon as centrioles have been duplicated, the protein is then degraded in early G1. (lookformedical.com)
  • These changes are orchestrated by a small number of master regulators, including the cyclin-dependent kinases (Cdks) and the anaphase-promoting complex/cyclosome (APC/C). Each Cdk or APC/C isoform has a large number of substrates, and the substrates of each isoform are modified in a specific order that leads to sequential substrate activation or inactivation. (biomedcentral.com)
  • Cyclin-dependent kinases (CDKs) are key regulatory enzymes, each consisting of a catalytic CDK subunit and an activating cyclin subunit. (kegg.jp)
  • however, the mechanisms underlying the regulation of cyclin F are poorly understood. (ox.ac.uk)
  • One such regulatory component is cyclin A which plays a role in the regulation of two different cell cycle stages. (wikipedia.org)
  • Tan IIA inhibited proliferation of mouse keratinocytes in a dose- and time-dependent manner and induced apoptosis, resulting in S phase arrest accompanied by down-regulation of pCdk2 and cyclin A protein expression. (hindawi.com)
  • Cdc2 regulation also involves positive feedback4, with active Cdc2-cyclin B stimulating its activator Cdc25 and inactivating its inhibitors Wee1 and Myt1. (sontaglab.org)
  • Previous evidence points to numerous components of the spindle assembly checkpoint and mitotic regulation playing a major role in several cancers [ 11 , 12 ]. (biomedcentral.com)
  • Cyclin-CDK inhibitors (CKIs), such as p16Ink4a, p15Ink4b, p27Kip1, and p21Cip1, are involved in the negative regulation of CDK activities, thus providing a pathway through which the cell cycle is negatively regulated. (kegg.jp)
  • Using a computational model based on multi-step ubiquitination, we then show how changes in the interaction between a single substrate and APC/C Cdc20 can alter the timing of degradation onset relative to APC/C Cdc20 activation, while ensuring a fast degradation rate. (biomedcentral.com)
  • Depending on how APC/C Cdc20 is partitioned among its substrates, competition can have minor or major effects on the degradation of certain substrates. (biomedcentral.com)
  • We show experimentally that increased expression of the early APC/C Cdc20 substrate Clb5 does not delay the degradation of the later substrate securin, arguing against a role for competition with Clb5 in establishing securin degradation timing. (biomedcentral.com)
  • The degradation timing of APC/C Cdc20 substrates depends on the multi-step nature of ubiquitination, differences in substrate-APC/C Cdc20 interactions, and competition among substrates. (biomedcentral.com)
  • Two observations made on the budding yeast Saccharomyces cerevisiae are inconsistent with this scenario: (i) anaphase occurs in the presence of high levels of kinase in cdc15 mutants and (ii) overproduction of a B-type mitotic cyclin causes arrest not in metaphase as previously reported but in telophase. (ox.ac.uk)
  • Numerical simulations reproduce the main features of wild-type mitotic cycles: patterns of protein accumulation and degradation, lengthening of later cycles, and arrest in interphase 14. (vt.edu)
  • The model is consistent with mutations that introduce subtle changes in the number of mitotic cycles before interphase arrest. (vt.edu)
  • They were shifted to 37°C to prearrest potential G1 and mitotic arrest mutants for 2 h then hydroxyurea was added to 10 mg/ml and cells were incubated at 37°C for an additional 5 h. (bibf1120.com)
  • Here, we observe that cyclin F is regulated by proteolysis through β-TrCP. (ox.ac.uk)
  • This conjecture is corroborated by the model, which indicates that sustained oscillations of the limit cycle type can arise in the cascade, provided that a threshold exists in the activation of cdc2 kinase by cyclin and in the activation of cyclin proteolysis by cdc2 kinase. (physiomeproject.org)
  • A single cyclin A gene has been identified in Drosophila while Xenopus, mice and humans contain two distinct types of cyclin A: A1, the embryonic-specific form, and A2, the somatic form. (wikipedia.org)
  • Cells were modified so their CDK2 was inhibited and their cyclin A2 gene was knocked out. (wikipedia.org)
  • The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. (novusbio.com)
  • These paclitaxel resistant ovarian cells demonstrate: (1) Increased IC 50 for paclitaxel and docetaxel (10 to 75-fold) and cross-resistance to anthracyclines (2) Reduced cell apoptosis in the presence of paclitaxel (3) Gene depletion involving mitotic regulators BUB1 mitotic checkpoint serine/threonine kinase, cyclin BI (CCNB1), centromere protein E (CENPE), and centromere protein F (CENPF), and (4) Functional data validating gene depletion among mitotic regulators. (biomedcentral.com)
  • β-TrCP recognizes cyclin F through a non-canonical degron site (TSGXXS) after its phosphorylation by casein kinase II. (ox.ac.uk)
  • This is thought to occur through the phosphorylation of particular DNA replication machinery components, such as CDC6, by the cyclin A/CDK2 complex. (wikipedia.org)
  • In mammals, Cyclin B1 associates with inactive p34cdc2, which facilitates phosphorylation of p34cdc2 at amino acids Thr-14 and Tyr-15. (nsjbio.com)
  • In the first cycle of the bicyclic cascade model, cyclin promotes the activation of cdc2 kinase through reversible dephosphorylation, and in the second cycle, cdc2 kinase activates a cyclin protease by reversible phosphorylation. (physiomeproject.org)
  • Cyclin A binds to the mitotic spindle poles in the centrosome however, the mechanism by which the complex is shuttled to the centrosome is not well understood. (wikipedia.org)
  • Coupling of microtubule nucleation in the centrosome with mitotic events in the nucleus was lost in the cyclin A knockout/CDK2 inhibited mutant cells. (wikipedia.org)
  • This study is the first to suggest a role of hBubR1 in controlling centrosome targeting of cyclin B 1 and timing of mitotic entry. (ewha.ac.kr)
  • Since the action of cyclin A/CDK2 inhibits that of cyclin E/CDK2, the sequential activation of cyclin E followed by the activation of cyclin A is important and tightly regulated in S phase. (wikipedia.org)
  • the APC then promotes cyclin degradation and resets Cdc2 to its inactive, interphase state. (sontaglab.org)
  • This paper examined whether Cdc2 activation is bistable, confirming that the response of Cdc2 to non-degradable cyclin B is temporally abrupt and switchlike, as would be expected if Cdc2 activation were bistable. (sontaglab.org)
  • That cyclin activates cdc2 kinase while the kinase triggers the degradation of cyclin has suggested that oscillations may originate from such a negative feedback loop [Felix, M. A., Labbe, J. C., Doree, M., Hunt, T. and Karsenti, E. (1990) Nature (London) 346, 379-382]. (physiomeproject.org)
  • The analysis shows how miototic oscillations may readily arise from time lags associated with these thresholds and from the delayed negative feedback provided by cdc2-induced cyclin degradation. (physiomeproject.org)
  • A minimal cascade model for the mitotic oscillator involving cyclin and cdc2 kinase, Albert Goldbeter, 1991, Proceedings of the National Academy of Sciences , 88, 9107-9111. (physiomeproject.org)
  • Minimal cascade model for the mitotic oscillations between cyclin and cdc2 kinase (M) during the cell cycle. (physiomeproject.org)
  • Since its initial discovery, homologues of cyclin A have been identified in numerous eukaryotes including Drosophila, Xenopus, mice, and in humans but has not been found in lower eukaryotes like yeast. (wikipedia.org)
  • Cyclin B Export to the Cytoplasm via the Nup62 Subcomplex and Subsequent Rapid Nuclear Import Are Required for the Initiation of Drosophila Male Meiosis. (nih.gov)
  • Centromere-associated protein-E (CENP-E) is an essential mitotic kinesin that is required for efficient, stable microtubule capture at kinetochores. (rupress.org)
  • Thus, CENP-E is required for enhancing recruitment of its binding partner BubR1 to each unattached kinetochore and for stimulating BubR1 kinase activity, implicating it as an essential amplifier of a basal mitotic checkpoint signal. (rupress.org)
  • Immunocytochemistry/ Immunofluorescence: Cyclin H Antibody (1B8) [H00000902-M01] - Analysis of monoclonal antibody to CCNH on HeLa cell. (novusbio.com)
  • Western Blot: Cyclin H Antibody (1B8) [H00000902-M01] - CCNH monoclonal antibody (M01), clone 1B8 Analysis of CCNH expression in HeLa. (novusbio.com)
  • WB analysis of HeLa cell lysate using GTX33611 Cyclin D1 antibody [RM241]. (genetex.com)
  • Immunofluorescent staining of PFA-fixed human HeLa cells with Cyclin B1 antibody (clone V92.1). (nsjbio.com)
  • Immunohistochemistry-Paraffin: Cyclin H Antibody (1B8) [H00000902-M01] - Analysis of monoclonal antibody to CCNH on formalin-fixed paraffin-embedded human testis. (novusbio.com)
  • Sandwich ELISA: Cyclin H Antibody (1B8) [H00000902-M01] - Detection limit for recombinant GST tagged CCNH is approximately 1ng/ml as a capture antibody. (novusbio.com)
  • IHC-P analysis of human tonsil tissue using GTX33611 Cyclin D1 antibody [RM241]. (genetex.com)
  • There are currently no references for Cyclin D1 antibody [RM241] (GTX33611) . (genetex.com)
  • Red=isotype control, Blue= Cyclin B1 antibody. (nsjbio.com)
  • SDS-PAGE analysis of purified, BSA-free Cyclin B1 antibody (clone V92.1) as confirmation of integrity and purity. (nsjbio.com)
  • This Cyclin B1 antibody is available for research use only. (nsjbio.com)
  • This antibody recognizes a protein of 55-62kDa, identified as Cyclin B1. (nsjbio.com)
  • Hamster protein was used as the immunogen for this Cyclin B1 antibody. (nsjbio.com)
  • Store the Cyclin B1 antibody at 2-8oC (with azide) or aliquot and store at -20oC or colder (without azide). (nsjbio.com)
  • During these mitotic cycles, there are barely detectable oscillations in the total level of B-type cyclins. (vt.edu)
  • Bifurcation analysis of the differential equations reveals the dependence of mitotic oscillations on cycle number, and how this dependence is altered by mutations. (vt.edu)
  • Among the diverse signaling outcomes associated with ubiquitination, the most well-established is the targeted degradation of substrates via the proteasome. (intechopen.com)
  • These chains are recognized by the proteasome, leading to substrate degradation [ 11 ]. (biomedcentral.com)
  • Cyclin A was first identified in 1983 in sea urchin embryos. (wikipedia.org)
  • Particularly in yeast, an organism where gluconeogenesis and glycolytic activity are intermittently coordinated, the multi-subunit GID E3 ligase complex specifically targets the surplus of gluconeogenic enzymes, including the conserved Fructose-1,6-bisphosphatase 1 (Fbp1), for proteasomal degradation. (elifesciences.org)
  • Cyclin A is the only cyclin that regulates multiple steps of the cell cycle. (wikipedia.org)
  • As the cell passes from G1 into S phase, cyclin A associates with CDK2, replacing cyclin E. Cyclin E is responsible for initiating the assembly of the pre-replication complex. (wikipedia.org)
  • In addition to initiating DNA synthesis, Cyclin A ensures that DNA is replicated once per cell cycle by preventing the assembly of additional replication complexes. (wikipedia.org)
  • and syncytial blastoderm mitotic cell cycle. (nih.gov)
  • Deletions of multiple GID subunits compromise cell proliferation, and this defect is accompanied by deregulation of critical cell cycle markers such as the retinoblastoma (Rb) tumor suppressor, phospho-Histone H3 and Cyclin A. We identify the negative regulator of pro-proliferative genes Hbp1 as a bonafide GID/CTLH proteolytic substrate. (elifesciences.org)
  • It also directly binds to BubR1, a kinetochore-associated kinase implicated in the mitotic checkpoint, the major cell cycle control pathway in which unattached kinetochores prevent anaphase onset. (rupress.org)
  • Xiao (cell department routine) mutants and determined a book mutant (and so are mixed up in degradation of Clb2 and the merchandise of both genes associate using the candida APC. (bibf1120.com)
  • Here, we have developed a novel computational model of human mitotic cell cycle, integrating diverse cellular mechanisms, for the purpose of generating new hypotheses and predicting new experiments designed to help understand complex diseases. (pharmafocusasia.com)
  • Prior to this work, no such comprehensive model of the human mitotic cell cycle existed. (pharmafocusasia.com)
  • We have developed a novel integrated computational model of human mitotic cell cycle for the purpose of understanding how the human mitotic protein-protein interaction network (Fig 1A) is altered during disease. (pharmafocusasia.com)
  • ATR-Chk1-mediated protein degradation of Cdc25A protein phosphatase is also a mechanism conferring intra-S-phase checkpoint activation. (kegg.jp)
  • Dysregulation of CDK8 (Cyclin-Dependent Kinase 8) and its regulatory partner CycC (Cyclin C) , two subunits of the conserved Mediator (MED) complex, have been linked to diverse human diseases such as cancer. (sdbonline.org)
  • These findings help establish the basic systems-level logic of the mitotic oscillator. (sontaglab.org)
  • ABSTRACT: A minimal model for the mitotic oscillator is presented. (physiomeproject.org)
  • Together, our results indicate that hBubR1 depletion triggers premature centrosomal localization of cyclin B 1 probably leading to premature mitotic entry. (ewha.ac.kr)
  • Localization to the chromocenters is mediated by an N-terminal domain, in addition we find that this domain may be involved in cyclin binding. (uni-bielefeld.de)
  • As expected, BubR1 depletion leads to degradation of cyclin B 1 in the G 2 phase. (ewha.ac.kr)
  • Here, we demonstrate that reducing BubR1 levels during the G 2 phase causes accelerated mitotic entry. (ewha.ac.kr)
  • Intriguingly, cyclin B 1 is prematurely targeted to centrosomes appearing at early G 2 phase in BubR1-depleted cells despite its low levels. (ewha.ac.kr)
  • While BUBR1 silencing rescues the mitotic phenotype induced by E2, p53 silencing or presence of E6/E7 (inactivating p53 and increasing BUBR1 levels respectively) both amplify it. (docksci.com)
  • The inactive Cyclin B1-p34cdc2 complex continues to accumulate in the cytoplasm until the completion of DNA synthesis, when Cdc25, a specific protein phosphatase, dephosphorylates amino acids Thr-14 and Tyr-15 of p34cdc2 rendering the complex active at the G2/M boundary. (nsjbio.com)
  • Enables cyclin-dependent protein serine/threonine kinase regulator activity. (nih.gov)
  • A family of serine/threonine kinase Aurora constitutes a key regulator in the orchestration of mitotic events. (lookformedical.com)
  • These filaments also bind and recruit cofactors whose activities help execute abscission and/or delay abscission timing in response to mitotic errors via the NoCut/Abscission checkpoint. (elifesciences.org)
  • New research has since debunked this assumption, shedding light on cyclin A/CDK2 migration to the centrosomes in late G2. (wikipedia.org)
  • The interaction between the cyclin box, a region conserved across cyclins, and a region of the CDK, called the PSTAIRE, confers the foundation of the cyclin-CDK complex. (wikipedia.org)
  • When the amount of cyclin A/CDK2 complex reaches a threshold level, it terminates the assembly of the pre-replication complex made by cyclin E/CDK2. (wikipedia.org)
  • As the amount of Cyclin A/CDK2 complex increases, the complex initiates DNA replication. (wikipedia.org)
  • This cyclin forms a complex with CDK7 kinase and ring finger protein MAT1. (novusbio.com)