Evidence map›Paper›PMID 16501598›Full record

ArticleOncogene2006

17-AAG, an Hsp90 inhibitor, causes kinetochore defects: a novel mechanism by which 17-AAG inhibits cell proliferation.

Y Niikura, S Ohta, K J Vandenbeldt, R Abdulle, B F McEwen, K Kitagawa

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

30 citing papers in PubMed, 68 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Effects of aneuploidy on cell behaviour and function.Nature reviews. Molecular cell biology · 2022
    Review
  7. Role of HSP90 in Cancer.International journal of molecular sciences · 2021
    Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Whole chromosome aneuploidy: big mutations drive adaptation by phenotypic leap.BioEssays : news and reviews in molecular, cellular and developmental biology · 2012
    Article
  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

6 authors at 3 institutions in 1 country.

Y NiikuraDepartment of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.
S Ohta
K J Vandenbeldt
R Abdulle
B F McEwen
K Kitagawa
St. Jude Children's Research Hospital · USAlbany State University · USNew York State Department of Health · US

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
Molecular Structure and Function of the Human Kinetochore Outer PlateR01GM066270 · NIGMS · WADSWORTH CENTER · PI MCEWEN, BRUCE F · 2002 to 2010
$2.9M
Kinetochore Function and Cell Cycle Progression RevisionR01GM068418 · NIGMS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI KITAGAWA, KATSUMI · 2003 to 2012
$2.5M
NCI NIH HHS CA21765NIGMS NIH HHS GM066270NIGMS NIH HHS GM68418
6 · The paper itself

Abstract

The Hsp90 inhibitor 17-allylaminogeldanamycin (17-AAG), which is currently in clinical trials, is thought to exert antitumor activity by simultaneously targeting several oncogenic signaling pathways. Here we report a novel mechanism by which 17-AAG inhibits cell proliferation, and we provide the first evidence that HSP90 is required for the assembly of kinetochore protein complexes in humans. 17-AAG caused delocalization of several kinetochore proteins including CENP-I and CENP-H but excluding CENP-B and CENP-C. Consistently, 17-AAG induced a mitotic arrest that depends on the spindle checkpoint and induced misalignment of chromosomes and aneuploidy. We found that HSP90 associates with SGT1 (suppressor of G2 allele of skp1; SUGT1) in human cells and that depletion of SGT1 sensitizes HeLa cells to 17-AAG. Overexpression of SGT1 restored the localization of specific kinetochore proteins and chromosome alignment in cells treated with 17-AAG. Biochemical and genetic results suggest that HSP90, through its interaction with SGT1 (SUGT1), is required for kinetochore assembly. Furthermore, time-course experiments revealed that transient treatment with 17-AAG between late S and G2/M phases causes substantial delocalization of CENP-H and CENP-I, a finding that strongly suggests that HSP90 participates in kinetochore assembly in a cell cycle-dependent manner.

Indexed as

BenzoquinonesCell Cycle ProteinsCell LineCell ProliferationGrowth InhibitorsHeLa CellsHSP90 Heat-Shock ProteinsHumansKinetochoresLactams, MacrocyclicRifabutinRNA, Small InterferingBenzoquinonesCell Cycle ProteinsGrowth InhibitorsHSP90 Heat-Shock ProteinsLactams, MacrocyclicRifabutinRNA, Small InterferingSUGT1 protein, humantanespimycin

Identifiers

PMID16501598
OpenAlexW2029663913

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.