• The spindle checkpoint ensures accurate chromosome segregation by monitoring kinetochore-microtubule attachment. (elsevierpure.com)
  • The ultimate goals of our studies are to understand how these proteins enable accurate chromosome segregation and to discover how they are coordinated with each other and with other aspects of cell physiology. (nih.gov)
  • There are several interactions that MAD2 shares with others, specifically, binding with Cdc20, in a vital protein-to-protein interaction. (prospecbio.com)
  • Unattached or tensionless kinetochores activate the checkpoint and enhance the production of the mitotic checkpoint complex (MCC) consisting of BubR1, Bub3, Mad2, and Cdc20. (elsevierpure.com)
  • The N-terminal region of BubR1 binds to both Cdc20 and Mad2, thus nucleating MCC formation. (elsevierpure.com)
  • Shugoshin is a Mad1/Cdc20-like interactor of Mad2. (nature.com)
  • This phenotype is associated with interaction of E2 with the Mitotic Checkpoint Complex (MCC) proteins Cdc20, MAD2 and BUBR1. (docksci.com)
  • Zeste white 10 (ZW10) was initially identified as a mitotic checkpoint protein involved in chromosome segregation, and then implicated in targeting cytoplasmic dynein and dynactin to mitotic kinetochores, but it is also important in non-dividing cells. (wikipedia.org)
  • In higher eukaryotes, cytoplasmic dynein is involved in silencing the SAC by removing the checkpoint proteins Mad2 and the Rod-Zw10-Zwilch complex (RZZ) from aligned kinetochores. (wikipedia.org)
  • The primary function of MAD2 is to accumulate at kinetochores, and generate a wait signal that functions to prevent the cell from progressing to the anaphase of the cell cycle until the appropriate moment, and this is integral to the process. (prospecbio.com)
  • Centromere-associated protein-E (CENP-E) is an essential mitotic kinesin that is required for efficient, stable microtubule capture at kinetochores. (rupress.org)
  • 2004). Different spindle checkpoint proteins monitor microtubule attachment and tension at kinetochores in Drosophila cells . (up.pt)
  • The encoded protein binds to centromeres during the prophase, metaphase, and early anaphase cell division stages and to kinetochore microtubules during metaphase. (wikipedia.org)
  • This exists primarily as a safeguard against chromosome segregation errors, and delays anaphase until all of the sister chromatid pairs have correctly attached. (prospecbio.com)
  • The presence of a single, lagging chromosome is sufficient to activate the checkpoint, producing a delay at the metaphase-anaphase transition until the last spindle attachment is made. (columbia.edu)
  • Prior to the first meiotic division, homologous chromosomes pair, synapse, and recombine to ensure their proper disjunction at anaphase I. Additionally, telomeres tethered at the nuclear envelope cluster in the bouquet configuration where they are subjected to dramatic pulling forces acting from outside of the nucleus. (biorxiv.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)
  • Mad1, Mad2, Mps1). (nih.gov)
  • The spindle assembly checkpoint promotes chromosome bi-orientation: A novel Mad1 role in chromosome alignment. (docksci.com)
  • In addition to this interaction, MAD2 also interacts with Chk1, which is integral across multiple points of the cell cycle process, and this is one of the key interactions that plays a massive role in the process. (prospecbio.com)
  • Faithful chromosome segregation relies on dynamic interactions between spindle microtubules and chromosomes. (docksci.com)
  • The PCM is an ordered lattice that anchors a large number of microtubule (MT)-associated proteins, many of which bear putative coiled-coil domains, a tertiary structure known to facilitate protein-protein interactions [ 4 ]. (biomedcentral.com)
  • APC/C-dependent ubiquitylation and action of the AAA-ATPase TRIP13 in conjunction with the MAD2-specific adaptor p31 comet liberate separase from SGO2-MAD2 in vitro. (nature.com)
  • Fig. 4: TRIP13-p31 comet -dependent disassembly liberates separase from SGO2-MAD2. (nature.com)
  • Mechanism for remodelling of the cell cycle checkpoint protein MAD2 by the ATPase TRIP13. (icr.ac.uk)
  • Centromere/kinetochore protein zw10 homolog is a protein that in humans is encoded by the ZW10 gene. (wikipedia.org)
  • Bod1 depletion does not affect the activity or localization of Aurora B but does cause mislocalization of the microtubule depolymerase mitotic centromere- associated kinesin and prevents its efficient phosphorylation by Aurora B. Therefore, Bod1 is a novel kinetochore protein that is required for the detection or resolution of syntelic attachments in mitotic spindles. (rupress.org)
  • Surprisingly, the nup2Δ ndj1Δ double mutant failed to segregate chromosomes, even though the meiotic program continued. (biorxiv.org)
  • SNAP-29: a general SNARE protein that inhibits SNARE disassembly and is implicated in synaptic transmission. (sdbonline.org)
  • SGO2-MAD2 can functionally replace securin and sequesters most separase in securin-knockout cells. (nature.com)
  • Investigating the proteinsresulting from mRNA translation would reveal how far the levels of functionally available proteins correlate with mRNAs and would offernovel insights into the changes oocytes undergo during maternal ageing. (gotomydoctor.com)
  • MAD2, standing for mitotic arrest deficient 2, is a spindle checkpoint protein that plays an integral role in the human body. (prospecbio.com)
  • Chromosome segregation errors during meiosis are the leading cause of birth defects and developmental delays in humans ( H assold and H unt 2001 ). (biorxiv.org)
  • Complete loss of the mitotic checkpoint results in embryonic lethality owing to chromosome mis-segregation in various organisms. (columbia.edu)
  • Whether partial loss of checkpoint control leads to more subtle rates of chromosome instability compatible with cell viability remains unknown. (columbia.edu)
  • Chromosome instability (CIN) is an increased rate where chromosome acquire alterations due to errors in cell division. (encyclopedia.pub)
  • Protein phosphatase 2A (PP2A) belongs to the superfamily of phosphoprotein phosphatases (PPPs) and catalyzes protein dephosphorylation by hydrolyzing Ser/Thr-linked phosphate ester bonds ( Heroes,2013 ). (eu.org)
  • During interphase, chromosomes are enclosed within nuclei, and exchange of all molecules between this compartment and the rest of the cell occurs through nuclear pore complexes (NPCs). (nih.gov)
  • During interphase, several kinetochore proteins stably bind to NPCs (e.g. (nih.gov)
  • Acute loss of securin and SGO2, but not of either protein individually, resulted in separase deregulation associated with premature cohesin cleavage and cytotoxicity. (nature.com)
  • We are interested in mechanisms of chromosome segregation. (nih.gov)
  • Since Boveri's theory that chromosome abnormalities promote cancer, studies have attempted to elucidate the mechanisms behind the origins of chromosomal aberrations [ 1 ] . (encyclopedia.pub)
  • These attachment sites are linked to actin-bundles that surround the nucleus via an Ndj1-Mps3-Csm4 protein bridge that spans the inner and outer nuclear membranes. (biorxiv.org)
  • Trafficking between the nucleus and cytoplasm occurs through nuclear pore complexes (NPCs), which consist of ca. thirty distinct proteins called nucleoporins. (nih.gov)
  • The asymmetrical distribution of Ran-GTP and Ran-GDP drives cargo transport between the nucleus and cytoplasm through karyopherins, a family of nuclear transport carrier proteins that bind to Ran-GTP. (nih.gov)
  • PP2A-mediated protein dephosphorylation is involved in a broad range of cellular processes including cell-cycle progression, cytoskeletal dynamics, and growth factor signalling. (eu.org)
  • Progression through the cell cycle is accompanied by dramatic changes in cellular content and behavior, and involves a large number of proteins and processes. (biomedcentral.com)
  • The APC/C is an E3 ubiquitin ligase that drives mitotic progression by promoting timely degradation of key regulatory proteins [ 3 ]. (biomedcentral.com)
  • Much of our current work concerns the RanBP2 complex, which consists of RanBP2 (a large nucleoporin that is also known as Nup358), SUMO-1-conjugated RanGAP1 (the activating protein for the Ran GTPase), and Ubc9 (the conjugating enzyme for the SUMO family of ubiquitin-like modifiers). (nih.gov)
  • Our current studies on this complex focus on functional dissection of the multiple domains within this large protein and on interacting proteins that may be essential for the function of the RanBP2 complex. (nih.gov)
  • Mitotic chromosome segregation requires the coordination of both regulatory and mechanical molecular machines and culminates in the delivery of two complete sets of chromosomes to two daughter cells. (rupress.org)
  • In humans there exist five isoforms of the B56 type regulatory subunit and they bind to their interacting proteins through a conserved LxxIxE motif. (eu.org)
  • Protein dephosphorylation by the PP2A phosphatase is mainly achieved through the interaction of its regulatory subunit with the associated proteins. (eu.org)
  • A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors. (lookformedical.com)
  • Here we report that deletion of one MAD2 allele results in a defective mitotic checkpoint in both human cancer cells and murine primary embryonic fibroblasts. (columbia.edu)
  • In addition HIV-1 Vpr protein alters the cell-cycle regulation by hijacking centrosome functions. (biomedcentral.com)
  • Practically, cycle regulation, chromosome stability and epigenetic F9 cells allow for the efficient metabolic labelling of the modification, in both mouse and human oocytes SILAC reference in vitro, overcoming the difficulty of directly labelling oocytes in vivo. (gotomydoctor.com)
  • Checkpoint-defective cells show premature sister-chromatid separation in the presence of spindle inhibitors and an elevated rate of chromosome mis-segregation events in the absence of these agents. (columbia.edu)
  • 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)
  • Gene ontology (GO) semantic analysis revealed a high similarityof the detected proteome (2324 proteins) to the transcriptome (22 334 mRNAs), although not all proteins had a cognate mRNA. (gotomydoctor.com)
  • Here we identified Nup2 in a pool of enriched proteins that co-purify with tagged Ndj1 from meiotic cell extracts. (biorxiv.org)
  • Targeted TPX2 increases chromosome missegregation and suppresses tumor cell growth in human prostate cancer. (separase.com)
  • The Human Papillomavirus (HPV) E2 protein, which inhibits the E6 and E7 viral oncogenes, is believed to have antioncogenic properties. (docksci.com)
  • An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. (lookformedical.com)
  • The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. (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)
  • The motif is conserved in essential proteins throughout the eukaryotic domain of life and also in human viruses, suggesting that the motifs are required for basic cellular function. (eu.org)
  • Depending on the type of abnormalities, it can be classified into numerical CIN (nCIN), characterized by chromosome gains and losses, and structural CIN (sCIN) represented by chromosome translocations [ 2 ] . (encyclopedia.pub)
  • Here we show that human shugoshin 2 (SGO2), an essential protector of meiotic cohesin with unknown functions in the soma 6 , 7 , is turned into a separase inhibitor upon association with SAC-activated MAD2. (nature.com)
  • Fig. 1: MAD2-dependent binding of human SGO2 to separase. (nature.com)