Evidence map›Paper›PMID 30303738›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2019

Phosphorylation of MCPH1 isoforms during mitosis followed by isoform-specific degradation by APC/C-CDH1.

Stephanie K Meyer, Michael Dunn, Daniel S Vidler, Andrew Porter, Peter G Blain, Paul A Jowsey

Abstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
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

6 authors.

Stephanie K MeyerNational Intitute for Health Research (NIHR) Health Protection Research Unit for Chemical and Radiation Threats and Hazards, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; and.
Michael DunnNational Intitute for Health Research (NIHR) Health Protection Research Unit for Chemical and Radiation Threats and Hazards, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; and.
Daniel S VidlerNational Intitute for Health Research (NIHR) Health Protection Research Unit for Chemical and Radiation Threats and Hazards, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; and.
Andrew PorterNewcastle University Protein and Proteome Analysis, Newcastle University, Newcastle upon Tyne, United Kingdom.
Peter G BlainNational Intitute for Health Research (NIHR) Health Protection Research Unit for Chemical and Radiation Threats and Hazards, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; and.
Paul A JowseyNational Intitute for Health Research (NIHR) Health Protection Research Unit for Chemical and Radiation Threats and Hazards, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; and.

Funding

Wellcome Trust
6 · The paper itself

Abstract

Microcephalin-1 (MCPH1) exists as 2 isoforms that regulate cyclin-dependent kinase-1 activation and chromosome condensation during mitosis, with MCPH1 mutations causing primary microcephaly. MCPH1 is also a tumor suppressor protein, with roles in DNA damage repair/checkpoints. Despite these important roles, there is little information on the cellular regulation of MCPH1. We show that both MCPH1 isoforms are phosphorylated in a cyclin-dependent kinase-1-dependent manner in mitosis and identify several novel phosphorylation sites. Upon mitotic exit, MCPH1 isoforms were degraded by the anaphase-promoting complex/cyclosome-CDH1 E3 ligase complex. Anaphase-promoting complex/cyclosome-CDH1 target proteins generally have D-Box or KEN-Box degron sequences. We found that MCPH1 isoforms are degraded independently, with the long isoform degradation being D-Box dependent, whereas the short isoform was KEN-Box dependent. Our research identifies several novel mechanisms regulating MCPH1 and also highlights important issues with several commercial MCPH1 antibodies, with potential relevance to previously published data.-Meyer, S. K., Dunn, M., Vidler, D. S., Porter, A., Blain, P. G., Jowsey, P. A. Phosphorylation of MCPH1 isoforms during mitosis followed by isoform-specific degradation by APC/C-CDH1.

Indexed as

Gene Expression RegulationMitosisAnaphase-Promoting Complex-CyclosomeAntigens, CDCadherinsCell CycleCell Cycle ProteinsChromatinCytoskeletal ProteinsHEK293 CellsHeLa CellsHumansNerve Tissue ProteinsProtein BindingProtein IsoformsProteolysisAnaphase-Promoting Complex-CyclosomeAntigens, CDCadherinsCDH1 protein, humanCell Cycle ProteinsChromatinCytoskeletal ProteinsMCPH1 protein, humanNerve Tissue ProteinsProtein Isoformsanaphasecell cycle regulationcyclin-dependent kinase-1microcephalin-1promoting complex/cyclosome

Identifiers

PMID30303738
PMCPMC6338662

What OpenQuestion holds

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Registered trials

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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.