CDC23

Summary

Gene Symbol: CDC23
Description: cell division cycle 23
Alias: ANAPC8, APC8, CUT23, cell division cycle protein 23 homolog, anaphase-promoting complex subunit 8, cell division cycle 23 homolog, cyclosome subunit 8
Species: human
Products:     CDC23

Top Publications

  1. 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. ..
  2. 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. ..
  3. Tran K, Mahr J, Choi J, Teodoro J, Green M, Spector D. Accumulation of substrates of the anaphase-promoting complex (APC) during human cytomegalovirus infection is associated with the phosphorylation of Cdh1 and the dissociation and relocalization of APC subunits. J Virol. 2008;82:529-37 pubmed
    ..Taken together, these results illustrate that HCMV has adopted multiple mechanisms to inactivate the APC, which underscores its importance for a productive infection. ..
  4. 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. ..
  5. Izawa D, Pines J. How APC/C-Cdc20 changes its substrate specificity in mitosis. Nat Cell Biol. 2011;13:223-33 pubmed publisher
    ..Here we show that Cdc20 binds to different sites on the APC/C depending on the SAC. Cdc20 requires APC3 and APC8 to bind and activate the APC/C when the SAC is satisfied, but requires only APC8 to bind the APC/C when the SAC is ..
  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. 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...
  8. 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. ..
  9. 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. ..

More Information

Publications55

  1. 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. ..
  2. Tran K, Kamil J, Coen D, Spector D. Inactivation and disassembly of the anaphase-promoting complex during human cytomegalovirus infection is associated with degradation of the APC5 and APC4 subunits and does not require UL97-mediated phosphorylation of Cdh1. J Virol. 2010;84:10832-43 pubmed publisher
    ..Immediate early viral gene expression was not sufficient for the degradation of APC4 and APC5, indicating that a viral early gene product(s), possibly in association with a de novo-synthesized cellular protein(s), is involved. ..
  3. 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. ..
  4. 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. ..
  5. 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. ..
  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. 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. ..
  8. 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. ..
  9. 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. ..
  10. 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. ..
  11. Bang L, Dasari V, Kim D, Gogoi R. Differential gene expression induced by Verteporfin in endometrial cancer cells. Sci Rep. 2019;9:3839 pubmed publisher
    ..b>CDC23 and BUB1B, two genes crucially involved in mitotic checkpoint progression, were found to be the pair with the best ..
  12. Clark E, Spector D. Studies on the Contribution of Human Cytomegalovirus UL21a and UL97 to Viral Growth and Inactivation of the Anaphase-Promoting Complex/Cyclosome (APC/C) E3 Ubiquitin Ligase Reveal a Unique Cellular Mechanism for Downmodulation of the APC/C Subunits A. J Virol. 2015;89:6928-39 pubmed publisher
    ..of all three platform subunits, APC1, APC4, and APC5, upon the depletion of any one of these subunits or of subunit APC8. Finally, we show that at a low multiplicity of infection, either UL97 or UL21a can partially complement a growth-..
  13. Li X, Zhong W, Xu Y, Yu B, Liu H. Silencing of lncRNA LINC00514 inhibits the malignant behaviors of papillary thyroid cancer through miR-204-3p/CDC23 axis. Biochem Biophys Res Commun. 2018;: pubmed publisher
    ..prediction, we identified that LINC00514 served as the sponge for miR-204-3p, and miR-204-3p directly targeted CDC23. Thus, LINC00514 promoted CDC23 expression via restraining miR-204-3p activity, leading to PTC progression...
  14. Suo L, Zhou Y, Jia L, Wu H, Zheng J, Lyu Q, et al. Transcriptome profiling of human oocytes experiencing recurrent total fertilization failure. Sci Rep. 2018;8:17890 pubmed publisher
    ..contrast, down regulated genes in the PN arrest group, included cell cycle genes, such as E2F4, DBF4, YWHAB, SKP2, CDC23, SMC3, CDC25A, CCND3, BUB1B, MDM2, CCNA2 and CDC7, together with homologous recombination related genes, such as ..
  15. Gao J, Yang S, Cheng W, Fu Y, Leng J, Yuan X, et al. GmILPA1, Encoding an APC8-like Protein, Controls Leaf Petiole Angle in Soybean. Plant Physiol. 2017;174:1167-1176 pubmed publisher
    ..characterization of Glycine max Increased Leaf Petiole Angle1 (GmILPA1), a gene encoding an APC8-like protein, which is a subunit of the anaphase-promoting complex/cyclosome in soybean (Glycine max)...
  16. Zhang M, Yao F, Luan H, Zhao W, Jing T, Zhang S, et al. APC/CCDC20 and APC/C play pivotal roles in the process of embryonic development in Artemia sinica. Sci Rep. 2016;6:39047 pubmed publisher
    ..play significant roles in the spindle assembly checkpoint, guiding ubiquitin-mediated degradation, together with CDC23. During the embryonic development of the brine shrimp, Artemia sinica, CDC20, CDH1 and CDC23 participate in cell ..
  17. Cianci M, Groves M, Barford D, Schneider T. Data collection with a tailored X-ray beam size at 2.69 Å wavelength (4.6 keV): sulfur SAD phasing of Cdc23(Nterm). Acta Crystallogr D Struct Biol. 2016;72:403-12 pubmed publisher
    ..Data collection at λ = 2.69 Å (4.6 keV) allowed the crystal structure determination by sulfur SAD phasing of Cdc23(Nterm), a subunit of the multimeric anaphase-promoting complex (APC/C)...
  18. 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. ..
  19. 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. ..
  20. 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. ..
  21. Lin Z, Tan C, Qiu Q, Kong S, Yang H, Zhao F, et al. Ubiquitin-specific protease 22 is a deubiquitinase of CCNB1. Cell Discov. 2015;1: pubmed
    ..Our study demonstrates that USP22 is a CCNB1 deubiquitinase, suggesting that targeting USP22 might be an effective approach to treat cancers with elevated CCNB1 expression. ..
  22. Lee S, Langhans S. Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis. BMC Cancer. 2012;12:44 pubmed publisher
  23. 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
    ..complex is composed of eight protein subunits, including BimE (APC1), CDC27 (APC3), CDC16 (APC6), and CDC23 (APC8). The remaining four human APC subunits, APC2, APC4, APC5, and APC7, as well as human CDC23, were cloned...
  24. 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. ..
  25. Wang W, Kirschner M. Emi1 preferentially inhibits ubiquitin chain elongation by the anaphase-promoting complex. Nat Cell Biol. 2013;15:797-806 pubmed publisher
    ..Chain elongation may be a particularly sensitive step for controlling degradation, and this study provides the first kinetic evidence for how it is inhibited. ..
  26. 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. ..
  27. 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. ..
  28. Walker M. Drug target discovery by gene expression analysis: cell cycle genes. Curr Cancer Drug Targets. 2001;1:73-83 pubmed
    ..an example of the identification of previously-unrecognized human cell cycle genes, CDCA1 through CDCA8, that are co-expressed with known cell cycle genes including CDC2, CDC7, CDC23, cyclin, MCAK, mki67a, topoisomerase II, and others.
  29. 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. ..
  30. 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. ..
  31. 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. ..
  32. 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. ..
  33. 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. ..
  34. Achari C, Winslow S, Ceder Y, Larsson C. Expression of miR-34c induces G2/M cell cycle arrest in breast cancer cells. BMC Cancer. 2014;14:538 pubmed publisher
    ..In addition, the levels of CDC23, an important mediator in mitotic progression, were suppressed following miR-34c expression, and siRNAs targeting ..
  35. 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. ..
  36. 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). ..
  37. 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. ..
  38. Fehr A, Gualberto N, Savaryn J, Terhune S, Yu D. Proteasome-dependent disruption of the E3 ubiquitin ligase anaphase-promoting complex by HCMV protein pUL21a. PLoS Pathog. 2012;8:e1002789 pubmed publisher
    ..This study reveals the HCMV protein pUL21a as a novel APC regulator and uncovers a unique viral mechanism to subvert APC activity. ..
  39. Zhang L, Rahbari R, He M, Kebebew E. CDC23 regulates cancer cell phenotype and is overexpressed in papillary thyroid cancer. Endocr Relat Cancer. 2011;18:731-42 pubmed publisher
    ..One of these genes was CDC23 that was upregulated in PTC in men compared with women...
  40. Sugimoto N, Kitabayashi I, Osano S, Tatsumi Y, Yugawa T, Narisawa Saito M, et al. Identification of novel human Cdt1-binding proteins by a proteomics approach: proteolytic regulation by APC/CCdh1. Mol Biol Cell. 2008;19:1007-21 pubmed
    ..Thus, in addition to SCF(Skp2) and cullin4-based ubiquitin ligases, APC/C(Cdh1) is a third ubiquitin ligase that plays a crucial role in proteolytic regulation of Cdt1 in mammalian cells. ..
  41. 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
    ..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...
  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. 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
    ..of the N-terminal APC1 loop implies that this loop controls interactions between the N-terminal domain of CDC20 and APC1 and APC8. These results reveal how APC/C phosphorylation enables CDC20 to bind and activate the APC/C in mitosis.
  44. Ban K, Torres J, Miller J, Mikhailov A, Nachury M, Tung J, et al. The END network couples spindle pole assembly to inhibition of the anaphase-promoting complex/cyclosome in early mitosis. Dev Cell. 2007;13:29-42 pubmed
    ..The organization of the APC/C on the spindle also provides a framework for understanding microtubule-dependent organization of protein destruction. ..
  45. Zhao N, Lai F, Fernald A, Eisenbart J, Espinosa R, Wang P, et al. Human CDC23: cDNA cloning, mapping to 5q31, genomic structure, and evaluation as a candidate tumor suppressor gene in myeloid leukemias. Genomics. 1998;53:184-90 pubmed
    ..A search revealed high homology to Saccharomyces cerevisiae CDC23, a TPR protein component of the APC...
  46. 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
    ..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...