Evidence map›Paper›PMID 24497846›Full record

ArticlePLoS genetics2014

A chaperone-assisted degradation pathway targets kinetochore proteins to ensure genome stability.

Franziska Kriegenburg, Visnja Jakopec, Esben G Poulsen, Sofie Vincents Nielsen, Assen Roguev, Nevan Krogan, Colin Gordon, Ursula Fleig, Rasmus Hartmann-Petersen

Abstract read
In one paragraph

Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing 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

35 citing papers in PubMed.

  1. Article
  2. HSP70-binding motifs function as protein quality control degrons.Cellular and molecular life sciences : CMLS · 2023
    Article
  3. Article
  4. Article
  5. Article
  6. Analysis and Interpretation of the Impact of Missense Variants in Cancer.International journal of molecular sciences · 2021
    Review
  7. Article
  8. Review
  9. Article
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  14. Article
  15. Article
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  20. Review
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

9 authors.

Franziska KriegenburgDepartment of Biology, University of Copenhagen, Copenhagen, Denmark.
Visnja JakopecLehrstuhl für Funktionelle Genomforschung der Mikroorganismen, Heinrich-Heine Universität, Düsseldorf, Germany.
Esben G PoulsenDepartment of Biology, University of Copenhagen, Copenhagen, Denmark.
Sofie Vincents NielsenDepartment of Biology, University of Copenhagen, Copenhagen, Denmark.
Assen RoguevDepartment of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, California, United States of America.
Nevan KroganDepartment of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, California, United States of America.
Colin GordonMRC Human Genetics Unit, Western General Hospital, Edinburgh, Scotland, United Kingdom.
Ursula FleigLehrstuhl für Funktionelle Genomforschung der Mikroorganismen, Heinrich-Heine Universität, Düsseldorf, Germany.
Rasmus Hartmann-PetersenDepartment of Biology, University of Copenhagen, Copenhagen, Denmark.

Funding

Medical Research CouncilWellcome Trust
6 · The paper itself

Abstract

Cells are regularly exposed to stress conditions that may lead to protein misfolding. To cope with this challenge, molecular chaperones selectively target structurally perturbed proteins for degradation via the ubiquitin-proteasome pathway. In mammals the co-chaperone BAG-1 plays an important role in this system. BAG-1 has two orthologues, Bag101 and Bag102, in the fission yeast Schizosaccharomyces pombe. We show that both Bag101 and Bag102 interact with 26S proteasomes and Hsp70. By epistasis mapping we identify a mutant in the conserved kinetochore component Spc7 (Spc105/Blinkin) as a target for a quality control system that also involves, Hsp70, Bag102, the 26S proteasome, Ubc4 and the ubiquitin-ligases Ubr11 and San1. Accordingly, chromosome missegregation of spc7 mutant strains is alleviated by mutation of components in this pathway. In addition, we isolated a dominant negative version of the deubiquitylating enzyme, Ubp3, as a suppressor of the spc7-23 phenotype, suggesting that the proteasome-associated Ubp3 is required for this degradation system. Finally, our data suggest that the identified pathway is also involved in quality control of other kinetochore components and therefore likely to be a common degradation mechanism to ensure nuclear protein homeostasis and genome integrity.

Indexed as

Genomic InstabilityKinetochoresProteolysisDNA-Binding ProteinsHSP70 Heat-Shock ProteinsMolecular ChaperonesProteasome Endopeptidase ComplexSchizosaccharomycesSchizosaccharomyces pombe ProteinsSignal TransductionTranscription FactorsUbiquitinUbiquitin-Protein LigasesATP dependent 26S proteaseBCL2-associated athanogene 1 proteinDNA-Binding ProteinsHSP70 Heat-Shock ProteinsMolecular ChaperonesProteasome Endopeptidase ComplexSan1 protein, S pombeSchizosaccharomyces pombe ProteinsTranscription FactorsUbiquitinUbiquitin-Protein LigasesUbr11 protein, S pombe

Identifiers

PMID24497846
PMCPMC3907333

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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.