Gene Symbol: CDC16
Description: cell division cycle 16
Alias: ANAPC6, APC6, CDC16Hs, CUT9, cell division cycle protein 16 homolog, anaphase-promoting complex, subunit 6, cell division cycle 16 homolog, cyclosome subunit 6
Species: human
Products:     CDC16

Top Publications

  1. Wang Q, Moyret Lalle C, Couzon F, Surbiguet Clippe C, Saurin J, Lorca T, et al. Alterations of anaphase-promoting complex genes in human colon cancer cells. Oncogene. 2003;22:1486-90 pubmed
    ..We report here gene alterations in several components of this complex in human colon cancer cells, including APC6/CDC16 and APC8/CDC23 which are known to be key function elements...
  2. Mansfeld J, Collin P, Collins M, Choudhary J, Pines J. APC15 drives the turnover of MCC-CDC20 to make the spindle assembly checkpoint responsive to kinetochore attachment. Nat Cell Biol. 2011;13:1234-43 pubmed publisher
    ..We conclude that APC15 mediates the constant turnover of CDC20 and MCCs on the APC/C to allow the SAC to respond to the attachment state of kinetochores. ..
  3. Kallio M, Weinstein J, Daum J, Burke D, Gorbsky G. Mammalian p55CDC mediates association of the spindle checkpoint protein Mad2 with the cyclosome/anaphase-promoting complex, and is involved in regulating anaphase onset and late mitotic events. J Cell Biol. 1998;141:1393-406 pubmed
    ..HeLa cells, p55CDC coimmunoprecipitates with three important elements of the M phase checkpoint machinery: Cdc27, Cdc16, and Mad2. p55CDC is required for binding Mad2 with the Cdc27 and Cdc16...
  4. Nilsson J, Yekezare M, Minshull J, Pines J. The APC/C maintains the spindle assembly checkpoint by targeting Cdc20 for destruction. Nat Cell Biol. 2008;10:1411-20 pubmed publisher
    ..Thus, ubiquitylation of human Cdc20 is not required to release it from the checkpoint complex, but to degrade it to maintain mitotic arrest. ..
  5. Gieffers C, Peters B, Kramer E, Dotti C, Peters J. Expression of the CDH1-associated form of the anaphase-promoting complex in postmitotic neurons. Proc Natl Acad Sci U S A. 1999;96:11317-22 pubmed
    ..On the basis of these results, we propose that the functions of APC(CDH1) are not restricted to controlling cell-cycle progression but may include the ubiquitination of yet unidentified substrates in differentiated cells. ..
  6. Kramer E, Scheuringer N, Podtelejnikov A, Mann M, Peters J. Mitotic regulation of the APC activator proteins CDC20 and CDH1. Mol Biol Cell. 2000;11:1555-69 pubmed
    ..These mechanisms can explain the temporal order of APC activation by CDC20 and CDH1 and may help to ensure that exit from mitosis is not initiated before anaphase has occurred. ..
  7. Kallio M, Beardmore V, Weinstein J, Gorbsky G. Rapid microtubule-independent dynamics of Cdc20 at kinetochores and centrosomes in mammalian cells. J Cell Biol. 2002;158:841-7 pubmed
  8. Sumara I, Vorlaufer E, Gieffers C, Peters B, Peters J. Characterization of vertebrate cohesin complexes and their regulation in prophase. J Cell Biol. 2000;151:749-62 pubmed
    ..These results suggest that vertebrate cohesins are regulated by a novel prophase pathway which is distinct from the APC pathway that controls cohesins in yeast. ..
  9. Tang Z, Li B, Bharadwaj R, Zhu H, Ozkan E, Hakala K, et al. APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex. Mol Biol Cell. 2001;12:3839-51 pubmed
    ..Surprisingly, with Ubc4 as the E2 enzyme, Zn(2+) ions alone are sufficient to catalyze the ubiquitination of cyclin B1. Therefore, the Zn(2+) ions of the RING finger family of ubiquitin ligases may be directly involved in catalysis. ..

More Information


  1. Sudakin V, Chan G, Yen T. Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2. J Cell Biol. 2001;154:925-36 pubmed
    ..We propose that the preformed interphase pool of MCC allows for rapid inhibition of APC/C when cells enter mitosis. Unattached kinetochores then target the APC/C for sustained inhibition by the MCC. ..
  2. Li Y, Gorbea C, Mahaffey D, Rechsteiner M, Benezra R. MAD2 associates with the cyclosome/anaphase-promoting complex and inhibits its activity. Proc Natl Acad Sci U S A. 1997;94:12431-6 pubmed
    ..Thus, MAD2 links the mitotic checkpoint pathway to the cyclin B destruction machinery which is critical in controlling the metaphase-anaphase transition. ..
  3. Ma H, Poon R. Orderly inactivation of the key checkpoint protein mitotic arrest deficient 2 (MAD2) during mitotic progression. J Biol Chem. 2011;286:13052-9 pubmed publisher
    ..In fact, the degradation of CDC20 is inextricably linked to the breakdown of MAD2(APC/C). These data extended our understanding of the checkpoint complexes during checkpoint silencing. ..
  4. Townsend K, Mason H, Blackford A, Miller E, Chapman J, Sedgwick G, et al. Mediator of DNA damage checkpoint 1 (MDC1) regulates mitotic progression. J Biol Chem. 2009;284:33939-48 pubmed publisher
    ..We suggest therefore that hMDC1 functionally regulates the normal metaphase-to-anaphase transition by modulating the Cdc20-dependent activation of the APC/C. ..
  5. Wang J, Dye B, Rajashankar K, Kurinov I, Schulman B. Insights into anaphase promoting complex TPR subdomain assembly from a CDC26-APC6 structure. Nat Struct Mol Biol. 2009;16:987-9 pubmed publisher
    ..Biophysical, structural and genetic studies presented here reveal that CDC26 stabilizes the structure of APC6, a core TPR protein required for APC integrity...
  6. Dube P, Herzog F, Gieffers C, Sander B, Riedel D, Müller S, et al. Localization of the coactivator Cdh1 and the cullin subunit Apc2 in a cryo-electron microscopy model of vertebrate APC/C. Mol Cell. 2005;20:867-79 pubmed
    ..We have further identified a large flexible domain in APC/C that adopts a different orientation upon Cdh1 binding. Cdh1 may thus activate APC/C both by recruiting substrates and by inducing conformational changes. ..
  7. Hagting A, den Elzen N, Vodermaier H, Waizenegger I, Peters J, Pines J. Human securin proteolysis is controlled by the spindle checkpoint and reveals when the APC/C switches from activation by Cdc20 to Cdh1. J Cell Biol. 2002;157:1125-37 pubmed
    ..Thus, defects in securin destruction alter chromosome segregation and may be relevant to the development of aneuploidy in cancer. ..
  8. Gmachl M, Gieffers C, Podtelejnikov A, Mann M, Peters J. The RING-H2 finger protein APC11 and the E2 enzyme UBC4 are sufficient to ubiquitinate substrates of the anaphase-promoting complex. Proc Natl Acad Sci U S A. 2000;97:8973-8 pubmed
    ..These results suggest that APC11 and UBC4 catalyze the formation of isopeptide bonds in APC-mediated ubiquitination reactions. ..
  9. Chan G, Jablonski S, Sudakin V, Hittle J, Yen T. Human BUBR1 is a mitotic checkpoint kinase that monitors CENP-E functions at kinetochores and binds the cyclosome/APC. J Cell Biol. 1999;146:941-54 pubmed
    ..The combined data indicate that hBUBR1 can potentially provide two checkpoint functions by monitoring CENP-E-dependent activities at the kinetochore and regulating cyclosome/APC activity. ..
  10. Tugendreich S, Tomkiel J, Earnshaw W, Hieter P. CDC27Hs colocalizes with CDC16Hs to the centrosome and mitotic spindle and is essential for the metaphase to anaphase transition. Cell. 1995;81:261-8 pubmed
    ..We find that the CDC27Hs and CDC16Hs proteins colocalize to the centrosome at all stages of the mammalian cell cycle, and to the mitotic spindle...
  11. Vodermaier H, Gieffers C, Maurer Stroh S, Eisenhaber F, Peters J. TPR subunits of the anaphase-promoting complex mediate binding to the activator protein CDH1. Curr Biol. 2003;13:1459-68 pubmed
    ..In analogy to PEX5, the different TPR subunits of the APC might function as receptors that interact with the C termini of regulatory proteins such as CDH1, CDC20, and APC10. ..
  12. Yu H, Peters J, King R, Page A, Hieter P, Kirschner M. Identification of a cullin homology region in a subunit of the anaphase-promoting complex. Science. 1998;279:1219-22 pubmed
    The anaphase-promoting complex is composed of eight protein subunits, including BimE (APC1), CDC27 (APC3), CDC16 (APC6), and CDC23 (APC8)...
  13. Kraft C, Herzog F, Gieffers C, Mechtler K, Hagting A, Pines J, et al. Mitotic regulation of the human anaphase-promoting complex by phosphorylation. EMBO J. 2003;22:6598-609 pubmed
    ..Of these, 32 sites are clustered in parts of Apc1 and the tetratricopeptide repeat (TPR) subunits Cdc27, Cdc16, Cdc23 and Apc7...
  14. Turnell A, Stewart G, Grand R, Rookes S, Martin A, Yamano H, et al. The APC/C and CBP/p300 cooperate to regulate transcription and cell-cycle progression. Nature. 2005;438:690-5 pubmed
    ..Taken together, our results define discrete roles for the APC/C-CBP/p300 complexes in growth regulation. ..
  15. Hayes M, Kimata Y, Wattam S, Lindon C, Mao G, Yamano H, et al. Early mitotic degradation of Nek2A depends on Cdc20-independent interaction with the APC/C. Nat Cell Biol. 2006;8:607-14 pubmed
    ..Thus, although Cdc20 is required for the degradation of Nek2A, it is not required for its recruitment and this renders its degradation insensitive to the mitotic checkpoint. ..
  16. Miller J, Summers M, Hansen D, Nachury M, Lehman N, Loktev A, et al. Emi1 stably binds and inhibits the anaphase-promoting complex/cyclosome as a pseudosubstrate inhibitor. Genes Dev. 2006;20:2410-20 pubmed
    ..The combination of a degron/E3 recognition site and an anti-ligase function in Emi1 suggests a general model for how E3 substrates evolve to become pseudosubstrate inhibitors. ..
  17. Finelli M, Aprile D, Castroflorio E, Jeans A, Moschetta M, Chessum L, et al. The epilepsy-associated protein TBC1D24 is required for normal development, survival and vesicle trafficking in mammalian neurons. Hum Mol Genet. 2019;28:584-597 pubmed publisher
    Mutations in the Tre2/Bub2/Cdc16 (TBC)1 domain family member 24 (TBC1D24) gene are associated with a range of inherited neurological disorders, from drug-refractory lethal epileptic encephalopathy and DOORS syndrome (deafness, ..
  18. Dibble C, Cantley L. Regulation of mTORC1 by PI3K signaling. Trends Cell Biol. 2015;25:545-55 pubmed publisher
    ..regulation of the tuberous sclerosis complex (TSC) complex (TSC complex) [composed of TSC1, TSC2, and Tre2-Bub2-Cdc16-1 domain family member 7 (TBC1D7)] switches on Rheb at the lysosome, where mTORC1 is activated...
  19. Li Y, Wang W, Cheng D, Wang T, Lu C, Chen J, et al. A New Member of the TBC1D15 Family from Chiloscyllium plagiosum: Rab GTPase-Activating Protein Based on Rab7 as a Substrate. Mar Drugs. 2015;13:2955-66 pubmed publisher
    ..Here, we demonstrate that the APSL sequence is present in the N-terminus of novel TBC (Tre-2, Bub2 and Cdc16) domain family, member 15 (TBC1D15) from Chiloscyllium plagiosum...
  20. Yan Q, Lin M, Huang W, Teymournejad O, Johnson J, Hays F, et al. Ehrlichia type IV secretion system effector Etf-2 binds to active RAB5 and delays endosome maturation. Proc Natl Acad Sci U S A. 2018;115:E8977-E8986 pubmed publisher
    ..Etf-2, although lacking a RAB GTPase-activating protein (GAP) Tre2-Bub2-Cdc16 (TBC) domain, contains two conserved TBC domain motifs, namely an Arg finger and a Gln finger, and site-directed ..
  21. Jørgensen N, Wojtaszewski J, Kjøbsted R. Serum Is Not Necessary for Prior Pharmacological Activation of AMPK to Increase Insulin Sensitivity of Mouse Skeletal Muscle. Int J Mol Sci. 2018;19: pubmed publisher
    ..AICAR stimulation did not enhance proximal insulin signaling, insulin-stimulated phosphorylation of Tre-2/BUB2/CDC16- domain family member 4 (TBC1D4) Ser711 was greater in prior AICAR-stimulated muscle compared to all other groups...
  22. Bajpai A, Feoktistova A, Chen J, McCollum D, Sato M, Carazo Salas R, et al. Dynamics of SIN asymmetry establishment. PLoS Comput Biol. 2013;9:e1003147 pubmed publisher
    ..but only one of these SPBs contains an active SIN in anaphase, while SIN is inactivated in the other by the Cdc16-Byr4 GAP complex...
  23. Oguchi M, Noguchi K, Fukuda M. TBC1D12 is a novel Rab11-binding protein that modulates neurite outgrowth of PC12 cells. PLoS ONE. 2017;12:e0174883 pubmed publisher
    ..protein (Rab-GAP), one of the key regulators of Rabs, and comprehensively screened 43 mammalian Tre-2/Bub2/Cdc16 (TBC)/Rab-GAP-domain-containing proteins (TBC proteins) for proteins that specifically localize on recycling ..
  24. Fentz J, Kjøbsted R, Birk J, Jordy A, Jeppesen J, Thorsen K, et al. AMPKα is critical for enhancing skeletal muscle fatty acid utilization during in vivo exercise in mice. FASEB J. 2015;29:1725-38 pubmed publisher
    ..membrane fatty acid binding protein) (by ∼17-40%), together with fully abolished TBC1D1 (tre-2/USP6, BUB2, cdc16 domain family member 1) Ser(237) phosphorylation during contraction/exercise in AMPKα mdKO mice, may impair FA ..
  25. Kristensen T, Fredholm M, Cirera S. Expression study of GLUT4 translocation-related genes in a porcine pre-diabetic model. Mamm Genome. 2015;26:650-7 pubmed publisher
    ..Three of the genes, TBC (Tre-2, BUB2, CDC16) 1 Domain Family Member 4 (TBC1D4), insulin receptor and GLUT4 showed altered expression in some of the tissues...
  26. Gallo L, Liao Y, Ruiz W, Clayton D, Li M, Liu Y, et al. TBC1D9B functions as a GTPase-activating protein for Rab11a in polarized MDCK cells. Mol Biol Cell. 2014;25:3779-97 pubmed publisher
    ..We observed that in the presence of Mg(2+) (2.5 mM), TBC1D9B interacted via its Tre2-Bub2-Cdc16 (TBC) domain with Rab11a, Rab11b, and Rab4a in a nucleotide-dependent manner...
  27. Dey S, Pollard T. Involvement of the septation initiation network in events during cytokinesis in fission yeast. J Cell Sci. 2018;131: pubmed publisher
    ..When high SIN activity persists far longer than normal on both SPBs in cdc16-116 mutant cells at 32°C, contractile rings assembled and constricted normally, but disassembled slowly, ..
  28. Qin J, Wang Z, Hoogeveen Westerveld M, Shen G, Gong W, Nellist M, et al. Structural Basis of the Interaction between Tuberous Sclerosis Complex 1 (TSC1) and Tre2-Bub2-Cdc16 Domain Family Member 7 (TBC1D7). J Biol Chem. 2016;291:8591-601 pubmed publisher
    ..Each TBC1D7 molecule interacts simultaneously with two parallel TSC1 helices from two TSC1 molecules, suggesting that TBC1D7 may stabilize the TSC complex by tethering the C-terminal ends of two TSC1 coiled-coils. ..
  29. Chen Q, Xie B, Zhu S, Rong P, Sheng Y, Ducommun S, et al. A Tbc1d1 Ser231Ala-knockin mutation partially impairs AICAR- but not exercise-induced muscle glucose uptake in mice. Diabetologia. 2017;60:336-345 pubmed publisher
    TBC1D1 (tre-2/USP6, BUB2, cdc16 domain family member 1) is a Rab GTPase-activating protein (RabGAP) that has been implicated in regulating GLUT4 trafficking...
  30. Chen L, Chen Q, Xie B, Quan C, Sheng Y, Zhu S, et al. Disruption of the AMPK-TBC1D1 nexus increases lipogenic gene expression and causes obesity in mice via promoting IGF1 secretion. Proc Natl Acad Sci U S A. 2016;113:7219-24 pubmed publisher
    Tre-2/USP6, BUB2, cdc16 domain family member 1 (the TBC domain is the GTPase activating protein domain) (TBC1D1) is a Rab GTPase activating protein that is phosphorylated on Ser(231) by the AMP-activated protein kinase (AMPK) in response ..
  31. Jeremian R, Chen Y, De Luca V, Vincent J, Kennedy J, Zai C, et al. Investigation of correlations between DNA methylation, suicidal behavior and aging. Bipolar Disord. 2017;19:32-40 pubmed publisher
    ..42×10-7 ) and in intron 3 of TRE2/BUB2/CDC16 domain family member 16 (TBC1D16) (P=6...
  32. Lin Y, Ke C, Wang Y, Chen M, Chen T, Ku W, et al. RAB10 Interacts with the Male Germ Cell-Specific GTPase-Activating Protein during Mammalian Spermiogenesis. Int J Mol Sci. 2017;18: pubmed publisher
    ..MGCRABGAP contains a conserved RABGAP catalytic domain, TBC (Tre2/Bub2/Cdc16). RABGAP family proteins regulate cellular function (e.g...
  33. Panagopoulos I, Gorunova L, Viset T, Heim S. Gene fusions AHRR-NCOA2, NCOA2-ETV4, ETV4-AHRR, P4HA2-TBCK, and TBCK-P4HA2 resulting from the translocations t(5;8;17)(p15;q13;q21) and t(4;5)(q24;q31) in a soft tissue angiofibroma. Oncol Rep. 2016;36:2455-2462 pubmed publisher
    ..The putative TBCK?P4HA2 protein would contain the kinase, the rhodanese?like domain, and the Tre?2/Bub2/Cdc16 (TBC) domains of TBCK together with the P4HA2 protein which is a component of the prolyl 4?hydroxylase...
  34. Leelatanawit R, Uawisetwathana U, Klanchui A, Khudet J, Phomklad S, Wongtriphop S, et al. Transcriptomic Analysis of Male Black Tiger Shrimp (Penaeus monodon) After Polychaete Feeding to Enhance Testicular Maturation. Mar Biotechnol (NY). 2017;19:125-135 pubmed publisher
    ..six of 11 differentially expressed gene identified by the microarray (HNRPUL1 and GCP4 in testes, MAT2B, CDC16, and CSN5 in vas deferens, and SLD5 in both organs) were validated by quantitative real-time PCR (qPCR) and found ..
  35. Paglialunga S, Simnett G, Robson H, Hoang M, Pillai R, Arkell A, et al. The Rab-GTPase activating protein, TBC1D1, is critical for maintaining normal glucose homeostasis and β-cell mass. Appl Physiol Nutr Metab. 2017;42:647-655 pubmed publisher
    Tre-2/USP6, BUB2, cdc16 domain family, member 1 (TBC1D1), a Rab-GTPase activating protein, is a paralogue of AS160, and has been implicated in the canonical insulin-signaling cascade in peripheral tissues...
  36. Jaillard S, Akloul L, Beaumont M, Hamdi Rozé H, Dubourg C, Odent S, et al. Array-CGH diagnosis in ovarian failure: identification of new molecular actors for ovarian physiology. J Ovarian Res. 2016;9:63 pubmed
    ..These genes are principally involved in cell division and chromosome segregation (SYCE1, CLASP1, CENP-A, CDC16), in ciliary development and/or function (RSPH1, KIF24), are linked with known gonadal genes or expressed in ..
  37. Boekhout M, Wolthuis R. Nek2A destruction marks APC/C activation at the prophase-to-prometaphase transition by spindle-checkpoint-restricted Cdc20. J Cell Sci. 2015;128:1639-53 pubmed publisher
    ..However, Mad2 depletion accelerated Nek2A destruction, showing that spindle checkpoint release further increases APC/C(Cdc20) catalytic activity. ..
  38. Ollendorff V, Donoghue D. The serine/threonine phosphatase PP5 interacts with CDC16 and CDC27, two tetratricopeptide repeat-containing subunits of the anaphase-promoting complex. J Biol Chem. 1997;272:32011-8 pubmed
    ..Three of the eight subunits of the anaphase-promoting complex (CDC16, CDC23, and CDC27) have been shown to be phosphorylated in M phase, and their phosphorylation is required for the ..
  39. Ivanova E, Mau Them F, Riazuddin S, Kahrizi K, Laugel V, Schaefer E, et al. Homozygous Truncating Variants in TBC1D23 Cause Pontocerebellar Hypoplasia and Alter Cortical Development. Am J Hum Genet. 2017;101:428-440 pubmed publisher
    ..TBC1D23 is a member of the Tre2-Bub2-Cdc16 (TBC) domain-containing RAB-specific GTPase-activating proteins (TBC/RABGAPs)...
  40. Qiao R, Weissmann F, Yamaguchi M, Brown N, VanderLinden R, Imre R, et al. Mechanism of APC/CCDC20 activation by mitotic phosphorylation. Proc Natl Acad Sci U S A. 2016;113:E2570-8 pubmed publisher
    ..These results reveal how APC/C phosphorylation enables CDC20 to bind and activate the APC/C in mitosis. ..
  41. Sørensen C, Lukas C, Kramer E, Peters J, Bartek J, Lukas J. A conserved cyclin-binding domain determines functional interplay between anaphase-promoting complex-Cdh1 and cyclin A-Cdk2 during cell cycle progression. Mol Cell Biol. 2001;21:3692-703 pubmed
    ..Collectively, these data provide a mechanistic explanation for the mutual functional interplay between cyclin A-Cdk2 and APC-Cdh1 and the first evidence that Cdh1 may activate the APC by binding specific substrates. ..
  42. Chang L, Zhang Z, Yang J, McLaughlin S, Barford D. Atomic structure of the APC/C and its mechanism of protein ubiquitination. Nature. 2015;522:450-454 pubmed publisher
    ..The structure of the APC/C with UbcH10-ubiquitin reveals insights into the initiating ubiquitination reaction. Our results provide a quantitative framework for the design of future experiments to investigate APC/C functions in vivo. ..
  43. Yamaguchi M, Yu S, Qiao R, Weissmann F, Miller D, VanderLinden R, et al. Structure of an APC3-APC16 complex: insights into assembly of the anaphase-promoting complex/cyclosome. J Mol Biol. 2015;427:1748-64 pubmed publisher
    ..Lamp contains the small subunits APC16, CDC26, and APC13, and tetratricopeptide repeat (TPR) proteins (APC7, APC3, APC6, and APC8) that homodimerize and stack with quasi-2-fold symmetry...
  44. Masuda K, Chiyoda T, Sugiyama N, Segura Cabrera A, Kabe Y, Ueki A, et al. LATS1 and LATS2 phosphorylate CDC26 to modulate assembly of the tetratricopeptide repeat subcomplex of APC/C. PLoS ONE. 2015;10:e0118662 pubmed publisher
    ..The T7 residue of CDC26 is critical for its interaction with APC6, a tetratricopeptide repeat-containing subunit of APC/C, and mutation of this residue to Asp (T7D) reduced the ..
  45. Chang L, Zhang Z, Yang J, McLaughlin S, Barford D. Molecular architecture and mechanism of the anaphase-promoting complex. Nature. 2014;513:388-393 pubmed publisher
    ..This transition is accompanied by increased flexibility of the cullin-RING subunits and enhanced affinity for UBCH10-ubiquitin, changes which may contribute to coactivator-mediated stimulation of APC/C E3 ligase activity. ..
  46. Jorgensen P, Gräslund S, Betz R, Stahl S, Larsson C, Hoog C. Characterisation of the human APC1, the largest subunit of the anaphase-promoting complex. Gene. 2001;262:51-9 pubmed
    ..A difference from this pattern is however seen for the APC6, which in some cases is more strongly expressed, suggesting a special function for this protein in certain tissues ..
  47. Yasui K, Arii S, Zhao C, Imoto I, Ueda M, Nagai H, et al. TFDP1, CUL4A, and CDC16 identified as targets for amplification at 13q34 in hepatocellular carcinomas. Hepatology. 2002;35:1476-84 pubmed
    ..3 of those genes, TFDP1, CUL4A (cullin 4A), and CDC16 (cell division cycle 16), showed distinct amplification and consequent over-expression in some cell lines...
  48. Listovsky T, Sale J. Sequestration of CDH1 by MAD2L2 prevents premature APC/C activation prior to anaphase onset. J Cell Biol. 2013;203:87-100 pubmed publisher
    ..Thus, MAD2L2 helps to ensure a robustly bistable switch between APC/C(CDC20) and APC/C(CDH1) during the metaphase-to-anaphase transition, thereby contributing to mitotic fidelity. ..
  49. Hames R, Wattam S, Yamano H, Bacchieri R, Fry A. APC/C-mediated destruction of the centrosomal kinase Nek2A occurs in early mitosis and depends upon a cyclin A-type D-box. EMBO J. 2001;20:7117-27 pubmed
    ..We propose that recognition of substrates by the APC/C-Cdc20 in early mitosis depends upon possession of an extended D-box motif. ..
  50. Kurasawa Y, Todokoro K. Identification of human APC10/Doc1 as a subunit of anaphase promoting complex. Oncogene. 1999;18:5131-7 pubmed
    ..These results strongly support the notion that human APC10/Doc1 may be one of the APC core subunits rather than the transiently associated regulatory factor. ..
  51. Binné U, Classon M, Dick F, Wei W, Rape M, Kaelin W, et al. Retinoblastoma protein and anaphase-promoting complex physically interact and functionally cooperate during cell-cycle exit. Nat Cell Biol. 2007;9:225-32 pubmed
    ..The results reveal an unexpected physical convergence between the pRB tumour-suppressor protein and E3 ligase complexes, and raise the possibility that pRB may direct APC/C to additional targets during pRB-mediated cell-cycle exit. ..
  52. Coster G, Hayouka Z, Argaman L, Strauss C, Friedler A, Brandeis M, et al. The DNA damage response mediator MDC1 directly interacts with the anaphase-promoting complex/cyclosome. J Biol Chem. 2007;282:32053-64 pubmed
    ..Our results reveal a link between the cellular response to DNA damage and cell cycle regulation, suggesting that MDC1, known to have a role in checkpoint regulation, executes part of this role by binding the APC/C. ..
  53. Kob R, Kelm J, Posorski N, Baniahmad A, von Eggeling F, Melle C. Regulation of the anaphase-promoting complex by the COP9 signalosome. Cell Cycle. 2009;8:2041-9 pubmed
    ..Furthermore, we detected a functional influence of the COP9 complex regarding the stability of several targets of the APC/C. Consistent with these data we showed a genetic instability of cells overexpressing CSN2. ..
  54. Zhang Z, Yang J, Kong E, Chao W, Morris E, da Fonseca P, et al. Recombinant expression, reconstitution and structure of human anaphase-promoting complex (APC/C). Biochem J. 2013;449:365-71 pubmed publisher
    ..Additional density present in the human APC/C structure, proximal to Apc3/Cdc27 of the TPR lobe, is assigned to the TPR subunit Apc7, a subunit specific to vertebrate APC/C. ..
  55. Uzunova K, Dye B, Schutz H, Ladurner R, Petzold G, Toyoda Y, et al. APC15 mediates CDC20 autoubiquitylation by APC/C(MCC) and disassembly of the mitotic checkpoint complex. Nat Struct Mol Biol. 2012;19:1116-23 pubmed publisher
    ..We propose that APC15 and Mnd2 negatively regulate APC/C coactivators and report generation of recombinant human APC/C. ..
  56. Chan G, Yen T. The mitotic checkpoint: a signaling pathway that allows a single unattached kinetochore to inhibit mitotic exit. Prog Cell Cycle Res. 2003;5:431-9 pubmed
    ..A single unattached kinetochore is proposed to amplify the "wait anaphase" signal through a kinase cascade involving checkpoint kinases such as hBubR1, hBub1 and Mps1. ..
  57. Brown N, Watson E, Weissmann F, Jarvis M, VanderLinden R, Grace C, et al. Mechanism of polyubiquitination by human anaphase-promoting complex: RING repurposing for ubiquitin chain assembly. Mol Cell. 2014;56:246-60 pubmed publisher
    ..Our data define mechanisms of APC/UBE2S-mediated polyubiquitination, reveal diverse functions of RING E3s and E2s, and provide a framework for understanding distinctive RING E3 features specifying ubiquitin chain elongation. ..
  58. Lim H, Dimova N, Tan M, Sigoillot F, King R, Shi Y. The G2/M regulator histone demethylase PHF8 is targeted for degradation by the anaphase-promoting complex containing CDC20. Mol Cell Biol. 2013;33:4166-80 pubmed publisher
    ..Taken together, these findings suggest that PHF8 is regulated by APC(cdc20) and plays an important role in the G2/M transition. ..
  59. Sedgwick G, Townsend K, Martin A, Shimwell N, Grand R, Stewart G, et al. Transcriptional intermediary factor 1? binds to the anaphase-promoting complex/cyclosome and promotes mitosis. Oncogene. 2013;32:4622-33 pubmed publisher
    ..Together these data define novel functions for TIF1? during mitosis and suggest that a reduction in APC/C ubiquitin ligase activity promotes SAC activation. ..
  60. Izawa D, Pines J. Mad2 and the APC/C compete for the same site on Cdc20 to ensure proper chromosome segregation. J Cell Biol. 2012;199:27-37 pubmed publisher
    ..Thus, we provide insights into how Cdc20 binds the APC/C and uncover a second mechanism by which the SAC inhibits the APC/C. ..
  61. Romano Moreno M, Rojas A, Williamson C, Gershlick D, Lucas M, Isupov M, et al. Molecular mechanism for the subversion of the retromer coat by the Legionella effector RidL. Proc Natl Acad Sci U S A. 2017;114:E11151-E11160 pubmed publisher
    ..from RidL inserts into a conserved pocket on VPS29 that is also used by cellular ligands, such as Tre-2/Bub2/Cdc16 domain family member 5 (TBC1D5) and VPS9-ankyrin repeat protein for VPS29 binding...
  62. Liu S, Chan G, Hittle J, Fujii G, Lees E, Yen T. Human MPS1 kinase is required for mitotic arrest induced by the loss of CENP-E from kinetochores. Mol Biol Cell. 2003;14:1638-51 pubmed
    ..Last, hMPS1 was found to associate with the anaphase promoting complex, thus raising the possibility that its checkpoint functions extend beyond the kinetochore. ..
  63. Holzmann J, Fuchs J, Pichler P, Peters J, Mechtler K. Lesson from the stoichiometry determination of the cohesin complex: a short protease mediated elution increases the recovery from cross-linked antibody-conjugated beads. J Proteome Res. 2011;10:780-9 pubmed publisher
    ..In summary, we show that the protease elution protocol increases the recovery from affinity beads and is compatible with quantitative measurements such as the stoichiometry determination of protein complexes. ..
  64. van Zon W, Ogink J, ter Riet B, Medema R, te Riele H, Wolthuis R. The APC/C recruits cyclin B1-Cdk1-Cks in prometaphase before D box recognition to control mitotic exit. J Cell Biol. 2010;190:587-602 pubmed publisher
    ..This suggests that the spindle checkpoint blocks D box recognition of APC/C-bound cyclin B1, whereas distinctive complexes between the N terminus of cyclin A and Cdc20 evade checkpoint control. ..
  65. Wu T, Merbl Y, Huo Y, Gallop J, Tzur A, Kirschner M. UBE2S drives elongation of K11-linked ubiquitin chains by the anaphase-promoting complex. Proc Natl Acad Sci U S A. 2010;107:1355-60 pubmed publisher
    ..UBE2S copurifies with APC; dominant-negative Ube2S slows down APC substrate degradation in functional cell-cycle extracts. We propose that Ube2S is a critical, unique component of the APC ubiquitination pathway. ..
  66. Jin L, Williamson A, Banerjee S, Philipp I, Rape M. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell. 2008;133:653-65 pubmed publisher
    ..We propose that recognition of similar motifs in substrates and ubiquitin enables the APC/C to assemble ubiquitin chains with the specificity and efficiency required for tight cell-cycle control. ..
  67. Lukas C, Sørensen C, Kramer E, Santoni Rugiu E, Lindeneg C, Peters J, et al. Accumulation of cyclin B1 requires E2F and cyclin-A-dependent rearrangement of the anaphase-promoting complex. Nature. 1999;401:815-8 pubmed
    ..These results implicate an E2F-dependent, cyclin A/Cdk2-mediated phosphorylation of Cdh1 in the timely accumulation of cyclin B1 and the coordination of cell-cycle progression during the post-restriction point period. ..
  68. Grossberger R, Gieffers C, Zachariae W, Podtelejnikov A, Schleiffer A, Nasmyth K, et al. Characterization of the DOC1/APC10 subunit of the yeast and the human anaphase-promoting complex. J Biol Chem. 1999;274:14500-7 pubmed
    ..DOC domains may therefore be important for reactions catalyzed by several types of ubiquitin-protein ligases. ..
  69. Kim H, Vassilopoulos A, Wang R, Lahusen T, Xiao Z, Xu X, et al. SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity. Cancer Cell. 2011;20:487-99 pubmed publisher
    ..Human breast cancers and HCC samples exhibited reduced SIRT2 levels compared with normal tissues. These data demonstrate that SIRT2 is a tumor suppressor through its role in regulating mitosis and genome integrity. ..
  70. Lara Gonzalez P, Scott M, Diez M, Sen O, Taylor S. BubR1 blocks substrate recruitment to the APC/C in a KEN-box-dependent manner. J Cell Sci. 2011;124:4332-45 pubmed publisher
    ..Thus, we propose a model in which the BubR1 KEN boxes play two very different roles, the first to promote MCC assembly and the second to block substrate recruitment to APC/C(Cdc20). ..
  71. Stroschein S, Bonni S, Wrana J, Luo K. Smad3 recruits the anaphase-promoting complex for ubiquitination and degradation of SnoN. Genes Dev. 2001;15:2822-36 pubmed
    ..Our studies elucidate an important mechanism and pathway for the degradation of SnoN and more importantly, reveal a novel role of the APC in the regulation of TGF-beta signaling. ..
  72. Tipton A, Ji W, Sturt Gillespie B, Bekier M, Wang K, Taylor W, et al. Monopolar spindle 1 (MPS1) kinase promotes production of closed MAD2 (C-MAD2) conformer and assembly of the mitotic checkpoint complex. J Biol Chem. 2013;288:35149-58 pubmed publisher
    ..Our results support the notion that MPS1 kinase promotes C-MAD2 production and subsequent MCC assembly to activate the SAC. ..
  73. Hein J, Nilsson J. Stable MCC binding to the APC/C is required for a functional spindle assembly checkpoint. EMBO Rep. 2014;15:264-72 pubmed publisher
    ..We thus show that stable MCC association with the APC/C is critical for a functional SAC. ..