Evidence map›Paper›PMID 27114510›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Mechanism of APC/CCDC20 activation by mitotic phosphorylation.

Renping Qiao, Florian Weissmann, Masaya Yamaguchi, Nicholas G Brown, Ryan VanderLinden, Richard Imre, Marc A Jarvis, Michael R Brunner, Iain F Davidson, Gabriele Litos and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed, 1 pooled it
11.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

98 citing papers in PubMed, 1 synthesis or guideline pooled it, 155 citations in OpenAlex.

  1. Pooled it
  2. Review
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  8. Article
  9. Article
  10. Cryo-EM structures of apo-APC/C and APC/CNature communications · 2024
    Article
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  14. Review
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38 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 9 institutions in 3 countries.

Renping QiaoResearch Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), 1030 Vienna, Austria;
Florian WeissmannResearch Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), 1030 Vienna, Austria;
Masaya YamaguchiDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105;
Nicholas G BrownDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105;
Ryan VanderLindenDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105; Howard Hughes Medical Institute, St. Jude Children's Research Hospital, Memphis, TN 38105;
Richard ImreInstitute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), 1030 Vienna, Austria;
Marc A JarvisResearch Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), 1030 Vienna, Austria;
Michael R BrunnerDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105;
Iain F DavidsonResearch Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), 1030 Vienna, Austria;
Gabriele LitosResearch Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), 1030 Vienna, Austria;
David HaselbachMax Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany; Department of 3D Electron Cryomicroscopy, Institute of Microbiology and Genetics, Georg-August Universität, 37077 Göttingen, Germany;
Karl MechtlerResearch Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), 1030 Vienna, Austria; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), 1030 Vienna, Austria;
Holger StarkMax Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany; Department of 3D Electron Cryomicroscopy, Institute of Microbiology and Genetics, Georg-August Universität, 37077 Göttingen, Germany; Jan-Michael.Peters@imp.ac.at Brenda.Schulman@stjude.org hstark1@gwdg.de.
Brenda A SchulmanDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105; Howard Hughes Medical Institute, St. Jude Children's Research Hospital, Memphis, TN 38105; Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Sciences Center, Memphis, TN 38163 Jan-Michael.Peters@imp.ac.at Brenda.Schulman@stjude.org hstark1@gwdg.de.
Jan-Michael PetersResearch Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), 1030 Vienna, Austria; Jan-Michael.Peters@imp.ac.at Brenda.Schulman@stjude.org hstark1@gwdg.de.
Vienna Biocenter · ATSt. Jude Children's Research Hospital · USResearch Institute of Molecular Pathology · ATAustrian Academy of Sciences · ATHoward Hughes Medical Institute · USInstitute of Molecular Biotechnology · ATMax Planck Institute for Biophysical Chemistry · DEUniversity of Göttingen · DEUniversity of Tennessee Health Science Center · US

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
E3-mediated Ubiquitin-like Protein LigationR37GM069530 · NIGMS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI SCHULMAN, BRENDA A · 2014 to 2018
$2.0M
Austrian Science Fund FWF T 816Austrian Science Fund FWF Z 196Howard Hughes Medical InstituteNCI NIH HHS P30 CA021765NIGMS NIH HHS R37 GM069530
6 · The paper itself

Abstract

Chromosome segregation and mitotic exit are initiated by the 1.2-MDa ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome) and its coactivator CDC20 (cell division cycle 20). To avoid chromosome missegregation, APC/C(CDC20) activation is tightly controlled. CDC20 only associates with APC/C in mitosis when APC/C has become phosphorylated and is further inhibited by a mitotic checkpoint complex until all chromosomes are bioriented on the spindle. APC/C contains 14 different types of subunits, most of which are phosphorylated in mitosis on multiple sites. However, it is unknown which of these phospho-sites enable APC/C(CDC20) activation and by which mechanism. Here we have identified 68 evolutionarily conserved mitotic phospho-sites on human APC/C bound to CDC20 and have used the biGBac technique to generate 47 APC/C mutants in which either all 68 sites or subsets of them were replaced by nonphosphorylatable or phospho-mimicking residues. The characterization of these complexes in substrate ubiquitination and degradation assays indicates that phosphorylation of an N-terminal loop region in APC1 is sufficient for binding and activation of APC/C by CDC20. Deletion of the N-terminal APC1 loop enables APC/C(CDC20) activation in the absence of mitotic phosphorylation or phospho-mimicking mutations. These results indicate that binding of CDC20 to APC/C is normally prevented by an autoinhibitory loop in APC1 and that its mitotic phosphorylation relieves this inhibition. The predicted location 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.

Indexed as

Anaphase-Promoting Complex-CyclosomeBinding SitesCdc20 ProteinsEnzyme ActivationHeLa CellsHumansMitosisMutagenesis, Site-DirectedPhosphorylationProtein BindingTransfectionAnaphase-Promoting Complex-CyclosomeCDC20 protein, humanCdc20 ProteinsAPC/CCDC20cell cyclemitosisphosphorylation

Identifiers

PMID27114510
PMCPMC4868491
OpenAlexW2404252289

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.