• As one of the checkpoint proteins, Bub3 delays the irreversible onset of anaphase through direction of kinetochore localization during prometaphase to achieve biorientation. (wikipedia.org)
  • Once errors are corrected, the spindle-assembly checkpoint is silenced, allowing anaphase onset to occur. (bvsalud.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)
  • Our current results imply that PIP4KIIγ may restrain MT depolymerization at the spindle pole through attenuating PLK1-mediated activation of MCAK before anaphase onset. (biomedcentral.com)
  • Bub3 is a crucial component in the formation of the mitotic spindle assembly complex, which forms a complex with other important proteins. (wikipedia.org)
  • This is controlled by the mitotic spindle checkpoint complex which operates as a feedback-response. (wikipedia.org)
  • In addition, coordination of MT polymerization/depolymerization at both ends to maintain the size and shape of mitotic spindles is also critical for the proper formation and function of the mitotic spindle. (biomedcentral.com)
  • At unattached kinetochores, a complex consisting of BubR1, Bub3, and Cdc20 interact with the Mad2-Cdc20 complex to inhibit the APC, thus inhibiting the formation of active APCCdc20. (wikipedia.org)
  • Bub3 has been shown to form complexes with Mad1-Bub1 and with Cdc20 (the interaction of which does not require intact kinetochores). (wikipedia.org)
  • When the SAC is activated, the production of the Bub3-Cdc20 complex is activated. (wikipedia.org)
  • BUB3 also phosphorylates: CDC20 (activator) and thereby inhibits the ubiquitin ligase activity of APC/C. MAD1L1, which usually interacts with BUB1 and BUBR1, and in turn the BUB1/BUB3 complex interacts with MAD1L1. (wikipedia.org)
  • Mitotic defects activate the spindle-assembly checkpoint, which inhibits the anaphase-promoting complex co-activator CDC20 to induce a prolonged cell cycle arrest1,2. (bvsalud.org)
  • Downstream translation initiation results in a truncated CDC20 isoform that is resistant to spindle-assembly-checkpoint-mediated inhibition and promotes mitotic exit even in the presence of mitotic perturbations. (bvsalud.org)
  • Rescue experimental results confirmed that PRMT6 promotes the ubiquitinated degradation of CDKN1B and cell proliferation via CDC20. (bvsalud.org)
  • Our findings illustrate that PRMT6, an epigenetic mediator, promotes CDC20 transcription via H3R2me2a to mediate the degradation of CDKN1B to facilitate GBM progression. (bvsalud.org)
  • This phenotype is associated with interaction of E2 with the Mitotic Checkpoint Complex (MCC) proteins Cdc20, MAD2 and BUBR1. (docksci.com)
  • The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. (icr.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)
  • Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. (icr.ac.uk)
  • The APC/C is an E3 ubiquitin ligase that drives mitotic progression by promoting timely degradation of key regulatory proteins [ 3 ]. (biomedcentral.com)
  • A family of cellular proteins that mediate the correct assembly or disassembly of polypeptides and their associated ligands. (lookformedical.com)
  • Depletion of PIP4KIIγ enhanced the spindle pole accumulation of mitotic centromere-associated kinesin (MCAK), a microtubule (MT)-depolymerizing kinesin, and resulted in a less stable spindle pole-associated MT. Depletion of MCAK can ameliorate PIP4KIIγ depletion-induced spindle abnormalities. (biomedcentral.com)
  • Reduction of APC/C activity results in loss of switch-like metaphase-to-anaphase transition and, strikingly, renders cells insensitive to chemical inhibition of MPS1 and genetic ablation of MAD2, both of which are essential for the SAC. (ku.dk)
  • Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. (icr.ac.uk)
  • Another function of BUB3 is to promote correct kinetochore-microtubule (K-MT) attachments when the spindle-assembly checkpoint is active. (wikipedia.org)
  • The spindle microtubule (MT) exhibits highly regulated dynamic instability, with frequent polymerization and depolymerization occurring at both the plus and minus ends. (biomedcentral.com)
  • Here, we challenge this view and show that HPV-18 E2 over-activates the Spindle Assembly Checkpoint (SAC) and induces DNA breaks in mitosis followed by aneuploidy. (docksci.com)
  • Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. (icr.ac.uk)
  • The pre-replication complex (pre-RC) assembly or the DNA replication licensing is the first step in DNA replication initiation, characterized by the sequential recruitment of ORCs, Cdc6, Cdt1 and MCMs to the DNA replication origins to form the pre-RC at the end of mitosis ( Bell and Dutta 2002 ). (intechopen.com)
  • The structural data suggested that Bub3 acts as a platform that mediates the interaction of SAC protein complexes. (wikipedia.org)
  • while Bub3 specifically binds Mad3 and Bub1, Rae1 has more promiscuous binding as it binds both the nuclear pore complex and Bub1. (wikipedia.org)
  • The components that are essential for the spindle assembly checkpoint in yeast have been determined to be Bub1, Bub3, Mad1, Mad2, Mad3, and the increasingly important Mps1 (a protein kinase). (wikipedia.org)
  • BUB3 forms a complex with BUB1 (BUB1/BUB3 complex) to inhibit the anaphase-promoting complex or cyclosome (APC/C) as soon as the spindle-assembly checkpoint is activated. (wikipedia.org)
  • The BUB1-BUB3 complex interacts with MAD1L1. (icr.ac.uk)
  • 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)
  • Mechanism for remodelling of the cell cycle checkpoint protein MAD2 by the ATPase TRIP13. (icr.ac.uk)
  • The 48 kDa subunit, RETINOBLASTOMA-BINDING PROTEIN 4, is also a component of several other protein complexes involved in chromatin remodeling. (lookformedical.com)
  • It is found as a subunit of protein complexes that are in involved in the enzymatic modification of histones including the Mi2 and Sin3 histone deacetylase complexes and the polycomb repressive complex 2. (lookformedical.com)
  • Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). (icr.ac.uk)
  • Stranglehold on the spindle assembly checkpoint: the human papillomavirus E2 protein provokes BUBR1-dependent aneuploidy. (docksci.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)
  • For correct segregation of the cells it is necessary for all mitotic spindles to attach correctly to the kinetochore of each chromosome. (wikipedia.org)
  • After kinetochore attachment is complete, the spindle checkpoint complexes (including the BubR1-Bub3) experience a decrease in concentration. (wikipedia.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)
  • The spindle assembly checkpoint promotes chromosome bi-orientation: A novel Mad1 role in chromosome alignment. (docksci.com)
  • Although initially discovered as a retinoblastoma binding protein it has an affinity for core HISTONES and is a subunit of chromatin assembly factor-1 and polycomb repressive complex 2. (lookformedical.com)
  • A previous screen of a human kinase and phosphatase shRNA library to select genes that mediate arsenite induction of spindle abnormalities resulted in the identification of phosphatidylinositol-5-phosphate 4-kinase type-2 gamma (PIP4KIIγ), a phosphatidylinositol 4,5-bisphosphate (PIP2)-synthesizing enzyme. (biomedcentral.com)
  • Consequently, depletion of PLK1 has been shown to counteract the PIP4KIIγ depletion-induced instability of spindle pole-associated MT and cell resistance to arsenite. (biomedcentral.com)
  • 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)
  • We have generated model systems to explore drug resistance in ovarian cancer, which have revealed a key pathway related to the spindle assembly checkpoint underlying paclitaxel resistance in ovarian cell lines. (biomedcentral.com)
  • Lastly, through gene expression profiling we have demonstrated disruption of the spindle assembly checkpoint in the paclitaxel resistant cell lines, indicating a potential therapeutic pathway. (biomedcentral.com)
  • Here, we aim to uncover the essential role and underlying mechanisms of PRMT6 in promoting glioblastoma (GBM) proliferation. (bvsalud.org)
  • During cell growth and proliferation, ubiquitin plays an outsized role in promoting progression through the cell cycle. (intechopen.com)
  • abstract = 'The anaphase-promoting complex/cyclosome (APC/C) and the spindle assembly checkpoint (SAC), which inhibits the APC/C, are essential determinants of mitotic timing and faithful division of genetic material. (ku.dk)
  • A histone chaperone that facilitates nucleosome assembly by mediating the formation of the histone octamer and its transfer to DNA. (lookformedical.com)
  • The precise regulations of pre-RC protein levels and assembly are effective ways to prevent reassembly of de novo MCM2-7 onto the replicated origins to re-license and re-replicate the genomic DNA in the subsequent phases of the same cell cycle ( Figure 1) . (intechopen.com)
  • Although they take part in the assembly process, molecular chaperones are not components of the final structures. (lookformedical.com)
  • in this arrangement, Bub3 acts as a key component of the SAC in the formation of an inhibitory complex. (wikipedia.org)