Evidence map›Paper›PMID 18592005›Full record

ArticleNeoplasia (New York, N.Y.)2008

Loss of CHFR in human mammary epithelial cells causes genomic instability by disrupting the mitotic spindle assembly checkpoint.

Lisa M Privette, Jingly Fung Weier, Ha Nam Nguyen, Xiaochun Yu, Elizabeth M Petty

Open access · goldAbstract read
In one paragraph

Article in Neoplasia (New York, N.Y.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.5field-weighted citation impact, top 12% 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

29 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
  2. Article
  3. Image-Based Analysis of Protein Stability.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2020
    Article
  4. Review
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  9. Review
  10. Review
  11. Elevated BUBR1 expression is associated with poor survival in early breast cancer patients: 15-year follow-up analysis.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2013
    Article
  12. Article
  13. CHFR: a key checkpoint component implicated in a wide range of cancers.Cellular and molecular life sciences : CMLS · 2012
    Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

5 authors at 3 institutions in 1 country.

Lisa M PrivetteDepartment of Human Genetics, University of Michigan, Ann Arbor, MI48109, USA.
Jingly Fung Weier
Ha Nam Nguyen
Xiaochun Yu
Elizabeth M Petty
University of Michigan–Ann Arbor · USStanford University · USUniversity of California, San Francisco · US

Funding

PREDOCTORAL TRAINING IN GENETICST32GM007544 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MORAN, JOHN V. · 1985 to 2022
$11.3M
Regulation of Ionizing Radiation-Induced DNA Damage ResponseR01CA130899 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LIU, YILUN · 2009 to 2023
$5.5M
Molecular Mechanisms of BRCA1-Dependent DNA Damage Response and TumorogenesisR01CA132755 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SHEN, BINGHUI · 2008 to 2019
$3.5M
The role of SEPT9 in cell proliferation and oncogenesisR01CA072877 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PETTY, ELIZABETH M. · 1997 to 2010
$2.4M
NCI NIH HHS R01 CA072877NCI NIH HHS R01CA072877NCI NIH HHS R01 CA130899NCI NIH HHS R01 CA132755NIGMS NIH HHS 5-T32-GM07544NIGMS NIH HHS T32 GM007544
6 · The paper itself

Abstract

CHFR is an E3 ubiquitin ligase and an early mitotic checkpoint protein implicated in many cancers and in the maintenance of genomic stability. To analyze the role of CHFR in genomic stability, by siRNA, we decreased its expression in genomically stable MCF10A cells. Lowered CHFR expression quickly led to increased aneuploidy due to many mitotic defects. First, we confirmed that CHFR interacts with the mitotic kinase Aurora A to regulate its expression. Furthermore, we found that decreased CHFR led to disorganized multipolar mitotic spindles. This was supported by the finding that CHFR interacts with alpha-tubulin and can regulate its ubiquitination in response to nocodazole and the amount of acetylated alpha-tubulin, a component of the mitotic spindle. Finally, we found a novel CHFR interacting protein, the spindle checkpoint protein MAD2. Decreased CHFR expression resulted in the mislocalization of both MAD2 and BUBR1 during mitosis and impaired MAD2/CDC20 complex formation. Further evidence of a compromised spindle checkpoint was the presence of misaligned metaphase chromosomes, lagging anaphase chromosomes, and defective cytokinesis in CHFR knockdown cells. Importantly, our results suggest a novel role for CHFR regulating chromosome segregation where decreased expression, as seen in cancer cells, contributes to genomic instability by impairing the spindle assembly checkpoint.

Indexed as

Genes, cdcAneuploidyAurora KinasesCalcium-Binding ProteinsCell Cycle ProteinsCells, CulturedChromosome SegregationEpithelial CellsGene DeletionGene Expression RegulationGenomic InstabilityHumansMad2 ProteinsMammary Glands, HumanModels, BiologicalNeoplasm ProteinsAurora KinasesCalcium-Binding ProteinsCell Cycle ProteinsCHFR protein, humanMAD2L1 protein, humanMad2 ProteinsNeoplasm ProteinsPoly-ADP-Ribose Binding ProteinsProtein Serine-Threonine KinasesRepressor ProteinsTubulinUbiquitin-Protein Ligases

Identifiers

PMID18592005
PMCPMC2435002
OpenAlexW1495998365

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.