• Without Cdk1-Clb2 complexes to phosphorylate proteins that are involved in spindle dynamics such as Sli15, Ase1, and Ask1, spindle elongation and chromosomal segregation are promoted, facilitating mitotic exit. (wikipedia.org)
  • We show that Cdk1 inhibition leads to fatal sister chromatid alignment errors and mitotic arrest in the spindle checkpoint. (eur.nl)
  • An aurora kinase that localizes to the CENTROSOME during MITOSIS and is involved in centrosome regulation and formation of the MITOTIC SPINDLE. (lookformedical.com)
  • In mitosis, it forms the two poles of the mitotic spindle upon which chromosomes are segregated. (le.ac.uk)
  • Plk1, the most thoroughly characterized member among the mammalian Plks, has multiple important roles in mitosis and cytokinesis, such as centrosome maturation, bipolar spindle formation, kinetochore-microtubule dynamics, activation of the anaphase promoting complex, chromosome segregation and execution of cytokinesis [ 3 , 4 , 13 ]. (oncotarget.com)
  • PP2A Cdc55 prevents the untimely activation of the mitotic exit in different ways: by the adaptation to the spindle assembly checkpoint, regulating the cohesin cleavage and by inhibiting Cdc14 release from the nucleolus ( Figure 1 ). (encyclopedia.pub)
  • At the onset of mitosis, centrosomes become the core structures of spindle poles and direct the formation of mitotic spindles. (biomedcentral.com)
  • In early mitosis, the cohesion between the two pairs of centrioles is broken and each of them participates in the formation of the mitotic spindle pole. (biomedcentral.com)
  • During mitosis the two centrosomes are present and form the mitotic spindle poles. (biomedcentral.com)
  • It is predicted that MCPH gene mutations may lead to the disease phenotype due to a disturbed mitotic spindle orientation, premature chromosomal condensation, signalling response as a result of damaged DNA, microtubule dynamics, transcriptional control or a few other hidden centrosomal mechanisms that can regulate the number of neurons produced by neuronal precursor cells. (biomedcentral.com)
  • Cyclin-dependent kinase 1 (Cdk1) is absolutely essential for cell division. (eur.nl)
  • A family of serine/threonine kinase Aurora constitutes a key regulator in the orchestration of mitotic events. (lookformedical.com)
  • Although we did not identify any highly Clb2-specific substrates, we found that Clb2-Cdk1 possessed higher intrinsic kinase activity than Clb5-Cdk1, enabling efficient phosphorylation of a broad range of mitotic Cdk1 targets. (nature.com)
  • Fisher, D. L. & Nurse, P. A single fission yeast mitotic cyclin B p34 cdc2 kinase promotes both S-phase and mitosis in the absence of G1 cyclins. (nature.com)
  • Targets of the cyclin-dependent kinase Cdk1. (nature.com)
  • Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors. (nature.com)
  • Schulman, B. A., Lindstrom, D. L. & Harlow, E. Substrate recruitment to cyclin-dependent kinase 2 by a multipurpose docking site on cyclin A. (nature.com)
  • 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)
  • 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)
  • 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)
  • 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)
  • In addition, compared to the mono-treatment, combination of Polo-like kinase 1 inhibition with anti-mitotic or DNA damaging agents boosts more severe mitotic defects, effectually triggers apoptosis and strongly inhibits proliferation of cancer cells with functional p53. (oncotarget.com)
  • The protein encoded by this gene is a putative serine/threonine kinase that localizes to the mitotic apparatus and complexes with cell cycle controller CDC2 kinase in early mitosis. (cancerindex.org)
  • The N-terminal region of the protein binds CDC2 to form a complex showing reduced H1 histone kinase activity, indicating a role as a negative regulator of CDC2/cyclin A. In addition, the C-terminal kinase domain binds to its own N-terminal region, suggesting potential negative regulation through interference with complex formation via intramolecular binding. (cancerindex.org)
  • Mitotic exit is an important transition point that signifies the end of mitosis and the onset of new G1 phase for a cell, and the cell needs to rely on specific control mechanisms to ensure that once it exits mitosis, it never returns to mitosis until it has gone through G1, S, and G2 phases and passed all the necessary checkpoints. (wikipedia.org)
  • However, sister chromatids failed to segregate, and cells reverted to mitosis once the inhibitors were washed away, indicating that a threshold level of the inhibitors needs to be achieved to trigger irreversible mitotic exit independently of cyclin degradations. (wikipedia.org)
  • 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)
  • a vegetative division, whereby each daughter cell is genetically identical to the parent cell (mitosis), and a reproductive cell division, whereby the number of chromosomes in the daughter cells is reduced by half to produce haploid gametes (meiosis). (mathisfunforum.com)
  • In cell biology, mitosis is a part of the cell cycle, in which, replicated chromosomes are separated into two new nuclei. (mathisfunforum.com)
  • The different stages of mitosis all together define the mitotic (M) phase of an animal cell cycle-the division of the mother cell into two genetically identical daughter cells. (mathisfunforum.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)
  • Many factors including cyclins, cyclin-dependent kinases (CDKs), ubiquitin ligases, inhibitors of cyclin-dependent kinases, and reversible phosphorylations regulate mitotic exit to ensure that cell cycle events occur in correct order with fewest errors. (wikipedia.org)
  • Despite different thresholds of Sic1 level that are required to trigger mitotic exit compared to G1-S transition, the level of Sic1 was shown to play a key role in regulating eukaryotic cell cycle by inhibiting the activity of CDKs. (wikipedia.org)
  • Cell-cycle events are controlled by cyclin-dependent kinases (CDKs), whose periodic activation is driven by cyclins. (nature.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)
  • 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)
  • Proteolytic degradation of cell cycle regulators and corresponding effects on the levels of cyclin-dependent kinases were proposed as a mechanism that promotes eukaryotic cell cycle and metaphase-to-anaphase transition in particular. (wikipedia.org)
  • Discoveries were made which indicated the importance of the level of the inhibitors of cyclin-dependent kinases in regulating eukaryotic cell cycle. (wikipedia.org)
  • 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)
  • Aurora kinases are found in all organisms in which their function has been conserved throughout evolution, namely the control of chromosome segregation. (lookformedical.com)
  • Brown, N. R., Noble, M. E., Endicott, J. A. & Johnson, L. N. The structural basis for specificity of substrate and recruitment peptides for cyclin-dependent kinases. (nature.com)
  • Many speculations were made with regard to the control mechanisms employed by a cell to promote the irreversibility of mitotic exit in a eukaryotic model organism, the budding yeast Saccharomyces cerevisiae. (wikipedia.org)
  • However, experiments using budding yeast cells with cdc28-as1, an INM-PP1 (ATP analog)-sensitive Cdk allele, proved that destruction of B-type cyclins (Clb) is not necessary for triggering irreversible mitotic exit. (wikipedia.org)
  • Here we compare the specificity of two budding yeast cyclins, the S-phase cyclin Clb5 and the M-phase cyclin Clb2, in the phosphorylation of 150 Cdk1 (Cdc28) substrates. (nature.com)
  • Later on, during late anaphase PP2A regulate the mitotic exit network (MEN in budding yeast or SIN in fission yeast). (encyclopedia.pub)
  • Cdc20 and Cdh1, which are the activators of APC, recruit substrates such as securin and B-type cyclins(Clb) for ubiquitination. (wikipedia.org)
  • 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)
  • 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)
  • In this theory, anaphase promoting complex (APC), a class of ubiquitin ligase, facilitates degradation of mitotic cyclins (Clb2) and anaphase-inhibiting factors (PDS1, CUT2) to promote mitotic exit. (wikipedia.org)
  • APC in association with Cdc20 (APC-Cdc20) ubiquitinates and targets mitotic cyclins (Clb2) for degradation at initial phase. (wikipedia.org)
  • Clb2 degradation did shorten the Cdk1-inhibition period required for triggering irreversible mitotic exit indicating that cyclin proteolysis contributes to the dynamic nature of the eukaryotic cell cycle due to slower timescale of its action but is unlikely to be the major determining factor in triggering irreversible cell cycle transitions. (wikipedia.org)
  • Donaldson, A. D. The yeast mitotic cyclin Clb2 cannot substitute for S phase cyclins in replication origin firing. (nature.com)
  • A- and B-type cyclins differentially modulate substrate specificity of cyclin-cdk complexes. (nature.com)
  • Dampening Cdk1 activation, by reducing gene expression or upon treatment with cell-permeable Cdk1 inhibitors, is also detrimental for proliferating cells, but has been associated with defects in mitotic progression, and the formation of aneuploid daughter cells. (eur.nl)
  • The APC/C is an E3 ubiquitin ligase that drives mitotic progression by promoting timely degradation of key regulatory proteins [ 3 ]. (biomedcentral.com)
  • Many of the side effects of chemotherapy can be traced to damage to normal cells that divide rapidly and are thus sensitive to anti-mitotic drugs: cells in the bone marrow, digestive tract and hair follicles. (worldsbest.rehab)
  • This phenotype is associated with interaction of E2 with the Mitotic Checkpoint Complex (MCC) proteins Cdc20, MAD2 and BUBR1. (docksci.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)
  • Homo sapiens BUB3 mitotic checkpoint protein (BUB3), transcript variant 2, mRNA. (dbcls.jp)
  • Once chromosomes are condensed and aligned at the metaphase plate, CDK1 activity is switched off by WEE1- and PKMYT1-mediated phosphorylation to allow sister chromatid separation, chromosome decondensation, reformation of the nuclear envelope and cytokinesis. (arigobio.cn)
  • In metaphase I, SMC1β, SMC3, SCP2, and SCP3 disappeared from the chromosome arms and accumulated around the centromeres, where they stayed until anaphase II. (rupress.org)
  • This prevents KIF4-dependent PRC1-1 translocation to astral microtubule tips and safeguards proper chromosome congression. (eur.nl)
  • 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)
  • 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)
  • Because the chromosomal t(14;18) translocation is found in the majority of patients with follicular lymphoma, bone marrow aspiration and chromosome analysis can also help establish the diagnosis. (medscape.com)
  • APC ubiquitinates nine-amino acid motif known as the destruction box (D box) in the NH2-terminal domain of mitotic cyclins for degradation by proteasome. (wikipedia.org)
  • Cdk1-inhibitors could induce mitotic exit even when degradation of B-type cyclins was blocked by expression of non-degradable Clbs or proteasome inhibitors. (wikipedia.org)
  • We conclude that cell death in response to Cdk1 inhibitors directly relates to chromosome alignment defects generated by insufficient repression of PRC1-1 and KIF4 during prometaphase. (eur.nl)
  • Clb5 specificity depended on an interaction between a hydrophobic patch in Clb5 and a short sequence in the substrate (the RXL or Cy motif). (nature.com)
  • Figure 2: Clb5 specificity depends on an interaction between the Clb5 hydrophobic patch and an RXL motif in the substrate. (nature.com)
  • Degradation timing and dynamics depend on substrate affinity for the enzyme as well as the catalytic rate at which the substrate is modified. (biomedcentral.com)
  • 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)
  • While degradation of Sic1 to a certain low level triggered the onset of S phase, accumulation of Sic1 to a certain high level was required to trigger irreversible mitotic exit. (wikipedia.org)
  • With the launch of the human proteome project (HPP), the association of Y chromosome proteins with pathological conditions has been increasingly explored. (biomedcentral.com)
  • The first described mitotic function of PP2A Cdc55 was its role in the activation of the phosphatase Cdc14 during anaphase. (encyclopedia.pub)
  • The mitotic reorganization of the Golgi is accompanied by a temporary block in Golgi functioning, as protein transport in and out of the Golgi stops. (biologists.com)
  • Our group has previously demonstrated the involvement of the alternatively spliced variants ERK1c and MEK1b (ERK1 is also known as MAPK3, and MEK1 as MAP2K1) in mitotic Golgi fragmentation. (biologists.com)
  • Centromere-associated protein-E (CENP-E) is an essential mitotic kinesin that is required for efficient, stable microtubule capture at kinetochores. (rupress.org)
  • Cell division gives rise to genetically identical cells in which the total number of chromosomes is maintained. (mathisfunforum.com)
  • On a larger scale, mitotic cell division can create progeny from multicellular organisms, such as plants that grow from cuttings. (mathisfunforum.com)
  • The amitotic or mitotic cell division is more atypical and diverse in the various groups of organisms such as protists (namely diatoms, dinoflagellates etc.) and fungi. (mathisfunforum.com)
  • Sic1 level was shown to play a major role in triggering irreversible mitotic exit (M-G1 transition) as well as in G1-S transition. (wikipedia.org)
  • The mouse Tzfp gene, mapped to chromosome 7 B2-B3, encodes a 465-amino acid transcription factor containing a conserved N-terminal BTB/POZ domain and three C-terminal PLZF-like C(2)H(2) zinc fingers. (lookformedical.com)
  • MicroRNA-34a gene (MIR-34A) that is located on chromosome 1p36 belongs to one of evolutionary-conserved miRNA families (MIR-34 family) that consists of three members: MIR-34A, MIR-34B, and MIR-34C [ 10 ]. (hindawi.com)
  • Understanding the molecular mechanisms underlying Y chromosome-related diseases can have a significant impact on the prevention, diagnosis, and treatment of diseases. (biomedcentral.com)
  • Before division can occur, the genomic information that is stored in chromosomes must be replicated, and the duplicated genome must be separated cleanly between cells. (mathisfunforum.com)
  • It was revealed as early as in the 1930s that the behavior of the whole chromosome and its fragments in cells varies. (actanaturae.ru)
  • Higher cells of download Hanging Sam: A Military and mental Canadian initiation in the 5'-end novo depends the lipid protein directly than NALP1-mediated deafness to the chain. (evakoch.com)