Evidence map›Paper›PMID 25789545›Full record

ArticleCell cycle (Georgetown, Tex.)2015

Therapeutic potential of mitotic interaction between the nucleoporin Tpr and aurora kinase A.

Akiko Kobayashi, Chieko Hashizume, Takayuki Dowaki, Richard W Wong

Open access · bronzeAbstract read
In one paragraph

Article in Cell cycle (Georgetown, Tex.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 19% 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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.

  1. Guideline
  2. Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Advances in the understanding of nuclear pore complexes in human diseases.Journal of cancer research and clinical oncology · 2024
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  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

4 authors at 2 institutions in 2 countries.

Akiko Kobayashia Laboratory of Molecular and Cellular Biology; Department of Biology ; Faculty of Natural Systems; Kanazawa University ; Kanazawa , Ishikawa , Japan.
Chieko Hashizume
Takayuki Dowaki
Richard W Wong
Natural (Czechia) · CZKanazawa University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Spindle poles are defined by centrosomes; therefore, an abnormal number or defective structural organization of centrosomes can lead to loss of spindle bipolarity and genetic integrity. Previously, we showed that Tpr (translocated promoter region), a component of the nuclear pore complex (NPC), interacts with Mad1 and dynein to promote proper chromosome segregation during mitosis. Tpr also associates with p53 to induce autophagy. Here, we report that Tpr depletion induces mitotic catastrophe and enhances the rate of tetraploidy and polyploidy. Mechanistically, Tpr interacts, via its central domain, with Aurora A but not Aurora B kinase. In Tpr-depleted cells, the expression levels, centrosomal localization and phosphorylation of Aurora A were all reduced. Surprisingly, an Aurora A inhibitor, Alisertib (MLN8237), also disrupted centrosomal localization of Tpr and induced mitotic catastrophe and cell death in a time- and dose-dependent manner. Strikingly, over-expression of Aurora A disrupted Tpr centrosomal localization only in cells with supernumerary centrosomes but not in bipolar cells. Our results highlight the mutual regulation between Tpr and Aurora A and further confirm the importance of nucleoporin function in spindle pole organization, bipolar spindle assembly, and mitosis; functions that are beyond the conventional nucleocytoplasmic transport and NPC structural roles of nucleoporins. Furthermore, the central coiled-coil domain of Tpr binds to and sequesters extra Aurora A to safeguard bipolarity. This Tpr domain merits further investigation for its ability to inhibit Aurora kinase and as a potential therapeutic agent in cancer treatment.

Indexed as

MitosisAntineoplastic AgentsAurora Kinase ACell Cycle CheckpointsCentrosomeChromosome SegregationHeLa CellsHumansNuclear Pore Complex ProteinsProtein BindingProtein Interaction Domains and MotifsProtein Interaction MappingProtein Kinase InhibitorsProto-Oncogene ProteinsRNA InterferenceSignal TransductionAntineoplastic AgentsAURKA protein, humanAurora Kinase ANuclear Pore Complex ProteinsProtein Kinase InhibitorsProto-Oncogene ProteinsTPR protein, humanalisertibAURKAcentriolecentrosometpr

Identifiers

PMID25789545
PMCPMC4614903
OpenAlexW1601417791

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.