• and Other Mitotic Proteins Are Decreased in DNA-Dependent Protein Kinase Catalytic Subunit-Deficient Cells and Rescued by Inhibition of the Anaphase-Promoting Complex/Cyclosome with proTAME but Not Apcin. (xenbase.org)
  • Protein phosphatase 1 and phosphatase 1 nuclear targeting subunit-dependent regulation of DNA-dependent protein kinase and non-homologous end joining. (xenbase.org)
  • The 48 kDa subunit, RETINOBLASTOMA-BINDING PROTEIN 4, is also a component of several other protein complexes involved in chromatin remodeling. (lookformedical.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)
  • 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)
  • Mammalian respiratory complex I (CI) is a 45-subunit, redox-driven proton pump that generates an electrochemical gradient across the mitochondrial inner membrane to power ATP synthesis in mitochondria. (biomed.news)
  • Characterization of the Anaphase Promoting Complex Subunit 4 (APC4) in Arabidopsis thaliana. (fapesp.br)
  • 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)
  • Structural basis for the subunit assembly of the anaphase-promoting complex. (ox.ac.uk)
  • This auto-regulation of Cdh1 could thus play a role in ensuring that the level of Cdh1 is reduced during G1 and GO, allowing it to be switched off at the correct time. (biu.ac.il)
  • 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)
  • The Anaphase Promoting complex/cyclosome co-activator, Cdh1, is a novel target of human Papillomavirus 16 E7 oncoprotein in cervical oncogenesis. (du.ac.in)
  • Cyclosome-mediated proteolysis is definitely activated in the metaphase-anaphase transition and its activity is managed during early G1 where it contributes to the prevention of a premature rise of Clbp-Cdc28p kinase activity (Irniger et al. (bio2009.org)
  • The anaphase promoter complex (APC) is a multiprotein complex - an ubiquitin E3 ubiquitin ligase - involved in ubiquitin-dependent proteolysis of cell cycle regulatory proteins, and in which we include the destruction of mitotic cyclins during the metaphase-anaphase transition. (fapesp.br)
  • Anaphase-promoting complex/cyclosome-dependent proteolysis of human cyclin A starts at the beginning of mitosis and is not subject to the spindle assembly checkpoint. (ximbio.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)
  • Treatment of M-phase extracts with a mutant cyclin B1-cdk1AF complex, refractory to inhibition by phosphorylation, impaired binding of the Anaphase Promoting Complex/Cyclosome (APC/C) to its co-activator Cdc20 and altered M-phase exit. (ox.ac.uk)
  • however, while these proteins share many structural features, emerging evidence suggests that these two co-activators may promote transcription of genes with different biological functions. (wikipedia.org)
  • One of the critical factors for the control of the protein levels during the cell cycle is the Anaphase Promoting Complex/Cyclosome (APC/C). This complex recognises proteins with specific signatures (or degrons) and targets them for degradation via the protein destruction machinery called the proteasome. (europa.eu)
  • The anaphase-promoting complex/cyclosome (APC/C) is a multisubunit ubiquitin ligase that regulates progression through the cell cycle by marking key cell division proteins for destruction. (ugent.be)
  • The Anaphase-Promoting Complex/Cyclosome (APC/C) ubiquitin ligase mediates degradation of cell cycle proteins during mitosis and G1. (biu.ac.il)
  • The APC/C is an E3 ubiquitin ligase that drives mitotic progression by promoting timely degradation of key regulatory proteins [ 3 ]. (biomedcentral.com)
  • This phenotype is associated with interaction of E2 with the Mitotic Checkpoint Complex (MCC) proteins Cdc20, MAD2 and BUBR1. (docksci.com)
  • Our structure explains how this TPR sub-complex, together with additional scaffolding subunits (Apc1, Apc4 and Apc5), coordinate the juxtaposition of the catalytic and substrate recognition module (Apc2, Apc11 and Apc10 (also known as Doc1)), and TPR-phosphorylation sites, relative to co-activator, regulatory proteins and substrates. (ox.ac.uk)
  • Silencing of the SAC during metaphase activates the ubiquitin ligase APC/C (anaphase-promoting complex, also known as the cyclosome) and results in the proteasomal destruction of the separase inhibitor securin 1 . (nature.com)
  • Is regulated by MAD2L1: in metaphase the MAD2L1-CDC20-APC/C ternary complex is inactive and in anaphase the CDC20-APC/C binary complex is active in degrading substrates. (thermofisher.com)
  • it is brought to the site via protein-protein interactions that are the result of its different structural domains complexing with other transcriptional co-activators. (wikipedia.org)
  • These pleiotropic effects are regulated by multiple layers of non-genetic regulation, including epigenetic silencing and post-transcriptional regulation by post-translational modifications (PTM) and non-coding RNAs [ 7 ]. (biomedcentral.com)
  • Consequently, motifs are indispensable for temporal, spatial, conditional and basal regulation at the transcriptional, post-transcriptional and post-translational level. (biomedcentral.com)
  • Therefore in budding candida down-regulation of Clbp-associated kinase is definitely brought about by transcriptional proteolytic and CKI mechanisms that are relieved in late G1 by Clnp-Cdc28p protein kinase activity. (bio2009.org)
  • the cyclin B-cdk 1 complex) is activated at M-phase onset by removal of inhibitory phosphorylation of cdk1 at thr-14 and tyr-15. (ox.ac.uk)
  • Finally, we examine co-clustering of the CDK consensus motifs with the 'cy' or RXL motif [ 17 ], which is known to be important in determining which CDK-cyclin complex will phosphorylate a given substrate. (biomedcentral.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 A is involved in the regulation of the cell cycle and is essential for progression through S phase. (ximbio.com)
  • The second option entails ubiquitin-mediated degradation of B-type cyclins which requires the cyclosome (Sudakin et al. (bio2009.org)
  • Securin degradation then unleashes separase to promote sister-chromatid separation. (biomedcentral.com)
  • Indeed, Hbp1 accumulates in cells lacking GID/CTLH activity, and Hbp1 physically interacts and is ubiquitinated in vitro by reconstituted GID/CTLH complexes. (elifesciences.org)
  • The majority of cell cycle regulators, including APC/C, as well as the genes regulating cells' responses to external cues, are very similar between Drosophila and mammals, although the genetic circuit in Drosophila is relatively simple and less complex compared to mammals. (europa.eu)
  • Among these genes is cdc34, the ubiquitin-conjugating enzyme of the Skp1/cullin/F-box (SCF) complex. (cornell.edu)
  • Solving the structure of protein complexes is particularly challenging when they contain many subunits. (nature.com)
  • One of the most complex ubiquitin ligases is the anaphase-promoting complex (APC) - a 1.5-megadalton assemblage of 1-2 copies of each of 13 different subunits, as well as two diffusible activators. (nature.com)
  • 1995 blue right-pointing triangle) or anaphase-promoting complex consisting of eight subunits including Apc1p/bimEp/slice4p (Peters et al. (bio2009.org)
  • Here, we identified all subunits of the mammalian GID/CTLH complex and provide a comprehensive map of its hierarchical organization and step-wise assembly. (elifesciences.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)
  • In order to develop a synthetic auxin signaling complex that was free from the complexities of varying protein family interactions, Keiko Torii and co-workers from the University of Washington and Nagoya University employed a bump-and-hole strategy. (garnetcommunity.org.uk)
  • In these diseases, association of CBP with β-catenin has been shown to promote cancer cell proliferation and disease aggressiveness, whereas p300/ β-catenin leads to cell differentiation and/ or apoptosis. (wikipedia.org)
  • promotes DNA double-strand break repair in distinct chromosomal contexts. (xenbase.org)
  • Finally, we contrast the regulatory properties of protein motifs and the regulatory elements of DNA and (pre-)mRNAs, advocating that co-regulation, co-operativity, and motif-driven regulatory programs are common mechanisms that emerge from the use of simple, evolutionarily plastic regulatory modules. (biomedcentral.com)
  • Members of the kinesin superfamily (KIF) 2, KIF2A, KIF2B, and MCAK (KIF2C) are MT depolymerizing motors and KIF10 (also known as CENP-E) is a plus-end directed kinesin promoting the elongation of the stabilized MTs [ 2 ]. (biomedcentral.com)
  • This approach makes it possible to pull out almost all components being part of any specific biological machinery and allows for an unbiased, genome-wide, identification of components and networks involved in, for example, stress granule regulation, protein phase separation condensate formation, protein quality control machinery, protein aggregate formation and inheritance and epigenetic silencing. (gu.se)
  • The chemical modification of RNA is a newly discovered epigenetic regulation mechanism in cells and plays a crucial role in a variety of biological processes. (biomedcentral.com)
  • In this chapter, we mainly discuss the coordination regulations between DNA replication initiation and other cell cycle events that ensure genomic integrity. (intechopen.com)
  • 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)
  • let-7 Overexpression leads to an increased fraction of cells in G2/M, direct down-regulation of Cdc34, and stabilization of Wee1 kinase in primary fibroblasts. (cornell.edu)
  • Consistent with this hypothesis, small interfering RNA-mediated down-regulation of Wee1 reversed the G(2)/M phenotype induced by let-7 overexpression. (cornell.edu)
  • We conclude that Cdc34 is a functional target of let-7 and that let-7 induces down-regulation of Cdc34, stabilization of the Wee1 kinase, and an increased fraction of cells in G(2)/M in primary fibroblasts. (cornell.edu)
  • 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)
  • MPF down-regulation required Ca(++)/calmodulin-dependent kinase II (CaMKII) and cAMP-dependent protein kinase (PKA) activities at meiosis and mitosis exit, respectively. (ox.ac.uk)
  • A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. (rush.edu)
  • Thus, our results identify an unexpected function of SGO2 in mitotically dividing cells and a mechanism of separase regulation that is independent of securin but still supervised by the SAC. (nature.com)
  • Cryo-EM structure of a metazoan separase-securin complex at near-atomic resolution. (nature.com)
  • The group is interested in early mitotic events which regulate the Anaphase Promoting Complex/Cyclosome (APC/C). MAD2L2 is a key protein for mitotic APC/C regulation, DNA damage tolerance (TLS) and other various cellular pathways. (zuckerman-scholars.org)
  • Protein kinases are critical to cellular signalling and post-translational gene regulation, but their biological substrates are difficult to identify. (biomedcentral.com)
  • Our biochemical and cellular analysis thus demonstrates that the GID/CTLH complex prevents cell cycle exit in G1, at least in part by degrading Hbp1. (elifesciences.org)
  • These results provide insights into the regulation of APC/C activity and demonstrate that the essentiality of the SAC is imposed by the strength of the APC/C. (ku.dk)
  • Biochemical reconstitution demonstrates that the mammalian complex possesses inherent E3 ubiquitin ligase activity, using Ube2H as its cognate E2. (elifesciences.org)
  • In this review, we provide a comprehensive introduction of the latest research progress on m6A modification and elucidate the origin of m6A modification, its regulation, biological functions and its correlation with the central nervous system and gliomas. (biomedcentral.com)
  • promotes DNA damage response pathway from a single-strand break. (xenbase.org)
  • SRSF2 Regulation of MDM2 Reveals Splicing as a Therapeutic Vulnerability of the p53 Pathway. (umassmed.edu)
  • Although these regulatory modules are physicochemically distinct, they share an evolutionary plasticity that has facilitated a rapid growth of their use and resulted in their ubiquity in complex organisms. (biomedcentral.com)
  • The CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. (thermofisher.com)
  • Role for non-proteolytic control of M-phase-promoting factor activity at M-phase exit. (ox.ac.uk)
  • 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)
  • PIP4KIIγ accumulates at the spindle pole before anaphase, and is required for the assembly of functional bipolar spindles. (biomedcentral.com)
  • We discuss how co-operativity allows simple static motifs to perform the conditional regulation that underlies decision-making in higher eukaryotic biological systems. (biomedcentral.com)
  • We explore MAD2L2's preferential complexes formation and its interactome in different pathways. (zuckerman-scholars.org)
  • Post-Doctoral position in MAD2L2's Role in Mitotic Regulation at the Group of Dr. Tamar Yulzary-Listovsky. (zuckerman-scholars.org)