• Cyclins are eukaryotic proteins that form holoenzymes with cyclin-dependent protein kinases (Cdk), which they activate. (wikipedia.org)
  • Cyclin A and E dependent kinase complexes also function to inhibit the E3 ubiquitin ligase APC/C activating subunit Cdh1 through phosphorylation, which stabilizes substrates such as cyclin A. The coordinated activation of this sequence of interrelated positive feedback loops through cyclins and cyclin dependent kinases drives commitment to cell division to and past the G1/S checkpoint. (wikipedia.org)
  • Progression through the cell cycle is driven by the oscillating activity of Cyclin Dependent Kinases (CDKs). (intechopen.com)
  • Cyclin-dependent protein kinases (Cdks) play central roles in regulating the production, activation, inactivation and destruction of these EPs. (nih.gov)
  • Activation of cyclin-dependent kinases requires association of the enzyme with a regulatory subunit referred to as a cyclin. (expasy.org)
  • It is the sequential activation and inactivation of cyclin-dependent kinases, through the periodic synthesis and destruction of cyclins, that provides the primary means of cell-cycle regulation. (expasy.org)
  • 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)
  • Cell cycle regulation is largely based on protein phospho-dephosphorylation events, catalyzed by cyclin dependent kinases (Cdks) and phosphatases (PPases), respectively. (encyclopedia.pub)
  • Rb reduces its binding to E2F and thereby allows E2F-mediated activation of the transcription of cyclin E and cyclin A, which bind to Cdk1 and Cdk2 respectively to create complexes that continue with Rb phosphorylation. (wikipedia.org)
  • Levasseur MD, Thomas C, Davies OR, Higgins JMG, Madgwick S. Aneuploidy in oocytes is prevented by sustained CDK1 activity through degron masking in cyclin B1 . (ncl.ac.uk)
  • EESR induced cell cycle arrest at G2/M phase in a dose-dependent manner by modulating cyclin B, cyclin-dependent kinase 1 (CDK1), and CDK inhibitor p21 expression. (jcpjournal.org)
  • 10 , 11 The major molecules responsible for G2/M transition are cyclin A /CDK1 and cyclin B/CDK1. (jcpjournal.org)
  • Cdk1 (cyclin-dependent kinase 1), also known as p34Cdc2 (cell division control protein kinase 2) depends on cyclin A and B and is triggered by a positive feedback loop at the end of G2 phase, which is the key event that initiates mitotic entry. (arigobio.cn)
  • Destruction of cyclin B during metaphase results in inactivation of Cdk1, allowing mitotic exit and cell division. (arigobio.cn)
  • CDK1/CDC2-cyclin-B controls pronuclear union in interphase fertilized eggs. (arigobio.cn)
  • During G2 and early mitosis, CDC25A/B/C-mediated dephosphorylation activates CDK1/cyclin complexes which phosphorylate several substrates that trigger at least centrosome separation, Golgi dynamics, nuclear envelope breakdown and chromosome condensation. (arigobio.cn)
  • Separase can alternatively be inhibited by association with Cdk1-cyclin B1 but the corresponding complex is scarce in early mitosis and cannot explain why vertebrate securin is dispensable. (uni-bayreuth.de)
  • 4) Pin1 catalyzed trans-to-cis isomerization of separase is essential for Cdk1-cyclin B1-dependent inhibition and explains why the kinase and securin bind separase in a mutually exclusive manner. (uni-bayreuth.de)
  • 5) Formation of the Cdk1-cyclin B1-separase complex is counter-acted by phosphorylation of cyclin B1 in early mitosis. (uni-bayreuth.de)
  • Dephosphorylation results in a second peak of Cdk1-cyclin B1-separase complex formation in late mitosis when most cyclin B1 has already been degraded. (uni-bayreuth.de)
  • 6) Upon destruction of this last cyclin B1 in early G1 phase, separase is released from the late Cdk1-cyclin B1-separase complex and triggers centriole disengagement, thereby licensing later centrosome duplication. (uni-bayreuth.de)
  • 13 The expression of CDK inhibitor p21 is upregulated by activated p53, resulting in the suppression of G2/M transition by the inactivation of cyclin/CDK complex. (jcpjournal.org)
  • Stabilization of β-Catenin can be achieved directly by mutation of phosphorylation sites in β-Catenin [ 15 ] or indirectly by inactivation of the destruction complex (mostly through APC inactivating mutations). (biomedcentral.com)
  • 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)
  • Studies with Mcl-1 phosphorylation mutants show that cyclin E/Cdk2-dependent phosphorylation of Mcl-1 residues on its PEST domain resulted in increased Mcl-1 stability (Thr92, and Thr163) and Bim binding (Ser64). (oncotarget.com)
  • 12 The activation of cyclin/CDK complex accelerates cell cycle progression, which are regulated by phosphorylation. (jcpjournal.org)
  • This destruction follows ubiquitylation by the APC/C-Cdc20 complex and depends on a novel destruction motif which is highly related to the extended D box present in cyclin A. Previous work has indicated that Nek2 may regulate centrosome cohesion through phosphorylation of the core centrosomal protein C-Nap1. (le.ac.uk)
  • Its output is outlined primarily by β-catenin's phosphorylation- and ubiquitylation-dependent proteasomal degradation, initiated by the multi-protein β-catenin destruction advanced. (medmk.com)
  • The abundance of cyclins is generally regulated by protein synthesis and degradation through APC/C- and CRL-dependent pathways. (wikipedia.org)
  • 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 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)
  • Cullins are major components of SCF complexes, and have been implicated in degradation of key regulatory molecules including Cyclin E, ß-catenin and Cubitus interruptus. (figshare.com)
  • Right here we describe the in vitro reconstitution of an energetic human β-catenin destruction advanced from purified parts, recapitulating advanced meeting, β-catenin modification, and degradation. (medmk.com)
  • 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)
  • Cyclin E knock-down restored ABT-737 sensitivity to acquired and inherently resistant Mcl-1-dependent tumor cells. (oncotarget.com)
  • Collectively, our findings identify a novel mechanism of cyclin E-mediated Mcl-1 regulation that provides a rationale for clinical use of Bcl-2 family and Cdk inhibitors for Mcl-1-dependent tumors. (oncotarget.com)
  • Recent studies have shown that cyclin-dependent kinase (CDK) inhibitors can have a tremendous impact on cell cycle progression in plants. (uni-bielefeld.de)
  • 8 , 9 Cell cycle program is regulated by cyclin/cyclin-dependent kinase (CDK) complexes. (jcpjournal.org)
  • PMID: 10102234 [PubMed - indexed for MEDLINE] 1: Exp Cell Res 2000 Feb 1;254(2):279-86 Cell cycle arrest induced by the vitamin D(3) analog EB1089 in NCI-H929 myeloma cells is associated with induction of the cyclin-dependent kinase inhibitor p27. (drlauda.at)
  • Analysis of G(1) regulatory proteins demonstrated that protein levels of CDK2, CDK4, cyclin D1, and cyclin A were decreased in a time-dependent manner, but not those of CDK6 and cyclin E, by EB1089. (drlauda.at)
  • ii) the specific destruction of Nek2A by the proteasome in early mitosis. (le.ac.uk)
  • Cyclin E/Cdk2 kinase activity is frequently deregulated in human cancers, resulting in impaired apoptosis. (oncotarget.com)
  • The kinase activity of this protein is controlled by cyclin accumulation and destruction through the cell cycle. (fcgportal.org)
  • The execution of anaphase and the destruction of CDC28 kinase activity therefore appear to take place independently of one another. (ox.ac.uk)
  • In response to stress, the yeast 1 and mammalian 2 cyclin C translocate from the nucleus to the cytoplasm, where it associates with the GTPase Drp1/Dnm1 to drive mitochondrial fragmentation and apoptosis. (bepress.com)
  • The inhibition of WNT/β-catenin signaling, apoptosis-related results (caspase-3 and alveolar destruction), and inflammation, particularly including caspase-3 and alveolar destruction, were more highly associated with polycyclic aromatic hydrocarbons in haze PM2.5. (tmu.edu.tw)
  • The p53 protein is an important tumor suppressor that is essential for regulating cell division, senescence, and self-destruction (apoptosis). (medlineplus.gov)
  • Here, we show that cyclin E/Cdk2 phosphorylates and stabilizes the pro-survival Bcl-2 family protein Mcl-1, a key cell death resistance determinant to the small molecule Bcl-2 family inhibitors ABT-199 and ABT-737, mimetics of the Bcl-2 homology domain 3 (BH3). (oncotarget.com)
  • Cyclin E levels were elevated and there was increased association of cyclin E/Cdk2 with Mcl-1 in ABT-737-resistant compared to parental cells. (oncotarget.com)
  • Kinase destruction is therefore implicated in the exit from mitosis rather than the entry into anaphase. (ox.ac.uk)
  • Recently, we have identified ULTRAVIOLET-B-INSENSITIVE4 (UVI4) as a plant-specific component of the APC/C. Here, we demonstrate that UVI4 uses conserved APC/C interaction motifs to counteract the activity of the CELL CYCLE SWITCH52 A1 (CCS52A1) activator subunit, inhibiting the turnover of the A-type cyclin CYCA2;3. (ugent.be)
  • In proliferating cells, cyclin D-Cdk4/6 complex accumulation is of great importance for cell cycle progression. (wikipedia.org)
  • The accumulation of both Cyclin and CKI proteins is tightly regulated at the level of transcription. (intechopen.com)
  • The conserved cyclin C and its kinase partner Cdk8 play a key role in this decision. (bepress.com)
  • In unstressed cells, the cyclin C‐Cdk8 kinase regulates transcription by associating with the Mediator of RNA polymerase II. (bepress.com)
  • Namely, cyclin D-Cdk4/6 complex partially phosphorylates retinoblastoma tumor suppressor protein (Rb), whose inhibition can induce expression of some genes (for example: cyclin E) important for S phase progression. (wikipedia.org)
  • Other than Rb, viral cyclin D-Cdk6 complex also targets p27Kip, a Cdk inhibitor of cyclin E and A. In addition, viral cyclin D-Cdk6 is resistant to Cdk inhibitors, such as p21CIP1/WAF1 and p16INK4a which in human cells inhibits Cdk4 by preventing it from forming an active complex with cyclin D. Cyclin D possesses a tertiary structure similar to other cyclins called the cyclin fold. (wikipedia.org)
  • Cyclin D levels in proliferating cells are sustained as long as the growth factors are present, a key player for G1/S transition is active cyclin D-Cdk4/6 complexes. (wikipedia.org)
  • One of the best known substrates of cyclin D/Cdk4 and -6 is the retinoblastoma tumor suppressor protein (Rb). (wikipedia.org)
  • One model proposes that cyclin D quantities, and thus cyclin D- Cdk4 and -6 activity, gradually increases during G1 rather than oscillating in a set pattern as do S and M cyclins. (wikipedia.org)
  • Destruction of the CDC28/CLB mitotic kinase is not required for the metaphase to anaphase transition in budding yeast. (ox.ac.uk)
  • 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)
  • The inhibition of β-catenin, TCF4 and cyclin D1 was observed invitro in response to haze PM2.5. (tmu.edu.tw)
  • Cyclin D is a member of the cyclin protein family that is involved in regulating cell cycle progression. (wikipedia.org)
  • Thomas C, Wetherall B, Levasseur MD, Harris RJ, Kerridge ST, Higgins JMG, Davies OR, Madgwick S. A prometaphase mechanism of securin destruction is essential for meiotic progression in mouse oocytes . (ncl.ac.uk)
  • In general, all stages of the cell cycle are chronologically separated in humans and are triggered by cyclin-Cdk complexes which are periodically expressed and partially redundant in function. (wikipedia.org)
  • In S. cerevisiae, oxidative stress triggers Med13 destruction 1 , which thereafter releases cyclin Ci nto the cytoplasm. (bepress.com)
  • 12. Cohen Todd J , Lee Kun, Rutkowski Lisa H, Strich Randy: Ask10p mediates the oxidative stress-induced destruction of the Saccharomyces cerevisiae C-type cyclin Ume3p/Srb11p. (unc.edu)
  • Cyclin E depletion in various human tumor cell-lines and cyclin E -/- mouse embryo fibroblasts showed decreased levels of Mcl-1 protein, with no change in Mcl-1 mRNA levels. (oncotarget.com)
  • Destruction of the bone structure resulted from tumor involvement. (medscape.com)
  • Cyclin D has no effect on G1/S transition unless it forms a complex with Cdk 4 or 6. (wikipedia.org)
  • promotes G2-M transition, and regulates G1 progress and G1-S transition via association with multiple interphase cyclins. (arigobio.cn)
  • We previously reported that the Mediator component Med13 anchors cyclin C in the nucleus 3 . (bepress.com)
  • In the absence of cyclin E, Mcl-1 ubiquitination was enhanced, leading to decreased protein stability. (oncotarget.com)
  • The behaviour of esp1 mutants shows in addition that kinase destruction can occur in the absence of anaphase completion. (ox.ac.uk)
  • A multienzyme system targets proteins for destruction through the covalent attachment of a multiubiquitin chain. (figshare.com)
  • Cyclin D protein is anywhere from 155 (in zebra mussel) to 477 (in Drosophila) amino acids in length. (wikipedia.org)
  • The three homologues, called cyclin D1, cyclin D2, and cyclin D3 are expressed in most proliferating cells and the relative amounts expressed differ in various cell types. (wikipedia.org)
  • Histologically, the tiny to medium-sized neoplastic lymphoid cells Rabbit Polyclonal to GPR115 (centrocyte-like cells) infiltrate around reactive follicles displaying marginal area growth pattern, which frequently infiltrate into gastric glands leading to destruction from the epithelial cells (lymphoepithelial lesions)[1,26]. (californiaehealth.org)
  • Multiple myeloma (MM) is a plasma cell malignancy in which monoclonal plasma cells proliferate in bone marrow, resulting in an overabundance of monoclonal paraprotein (M protein), destruction of bone, and displacement of other hematopoietic cell lines. (medscape.com)
  • In our patient the vitamin B12 deficiency may be related to a displacement or destruction of parietal cells by malignant plasma cells. (drlauda.at)
  • The first five-helix bundle is a conserved cyclin box, a region of about 100 amino acid residues on all cyclins, which is needed for Cdk binding and activation. (wikipedia.org)
  • Suppression of β-catenin levels, activation of caspase-3 and alveolar destruction, as well as IL-6, TNF-α and IFN-γ production, were observed in the lungs. (tmu.edu.tw)
  • In addition, Cyclin and CKI proteins are controlled at the level of their destruction. (intechopen.com)
  • 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)