Evidence map›Paper›PMID 30737284›Full record

ArticleThe Journal of biological chemistry2019

The co-chaperone UNC45A is essential for the expression of mitotic kinase NEK7 and tumorigenesis.

Nada H Eisa, Yasmeen Jilani, Kashish Kainth, Priscilla Redd, Su Lu, Oulia Bougrine, Houssein Abdul Sater, Chaitanya A Patwardhan, Austin Shull, Huidong Shi and 11 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

25 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Hsp90: Bringing it all together.Cell stress & chaperones · 2025
    Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. A myosin chaperone, UNC-45A, is a novel regulator of intestinal epithelial barrier integrity and repair.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    Article
  14. In Mitosis You Are Not: The NIMA Family of Kinases inInternational journal of molecular sciences · 2022
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Checking NEKs: Overcoming a Bottleneck in Human Diseases.Molecules (Basel, Switzerland) · 2020
    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

21 authors at 4 institutions in 4 countries.

Nada H EisaFrom the Georgia Cancer Center.
Yasmeen JilaniFrom the Georgia Cancer Center.
Kashish KainthFrom the Georgia Cancer Center.
Priscilla ReddFrom the Georgia Cancer Center.
Su LuFrom the Georgia Cancer Center.
Oulia Bougrinethe Department of Pathology, Augusta University, CN-3151, Augusta, Georgia 30912.
Houssein Abdul Saterthe Department of Pathology, Augusta University, CN-3151, Augusta, Georgia 30912.
Chaitanya A PatwardhanFrom the Georgia Cancer Center.
Austin ShullFrom the Georgia Cancer Center.ORCID 0000-0001-5111-2908
Huidong ShiFrom the Georgia Cancer Center.
Kebin Liuthe Biochemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt 35516.
Nehal M Elsherbinythe Biochemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt 35516.
Laila A Eissathe Biochemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt 35516.
Mamdouh M El-Shishtawythe Biochemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt 35516.
Anatolij HoruzskoFrom the Georgia Cancer Center.
Roni BollagFrom the Georgia Cancer Center.ORCID 0000-0003-4963-6619
Nita MaihleFrom the Georgia Cancer Center.
Joan Roigthe Institut de Biologia Molecular de Barcelona (IBMB-CSIC), Parc Científic de Barcelona, c/Baldiri i Reixac, 10-12, 08028 Barcelona, Spain.ORCID 0000-0002-3872-4712
Hasan KorkayaFrom the Georgia Cancer Center.ORCID 0000-0002-0719-5862
John K CowellFrom the Georgia Cancer Center.
Ahmed ChadliFrom the Georgia Cancer Center, achadli@augusta.edu.
National Cancer Center of Georgia · GEMansoura University · EGAugusta University Health · USInstitut de Biologia Molecular de Barcelona · ES

Funding

TREM-1 and Its Implications to CancerR01CA172230 · NCI · AUGUSTA UNIVERSITY · PI HORUZSKO, ANATOLIJ · 2014 to 2018
$1.6M
Targeting the core components of the Hsp90 chaperoning machineR01GM102443 · NIGMS · AUGUSTA UNIVERSITY · PI CHADLI, AHMED · 2012 to 2014
$743k
NCI NIH HHS R01 CA172230NIGMS NIH HHS R01 GM102443
6 · The paper itself

Abstract

Cumulative evidence suggests that the heat shock protein 90 (Hsp90) co-chaperone UNC-45 myosin chaperone A (UNC45A) contributes to tumorigenesis and that its expression in cancer cells correlates with proliferation and metastasis of solid tumors. However, the molecular mechanism by which UNC45A regulates cancer cell proliferation remains largely unknown. Here, using siRNA-mediated gene silencing and various human cells, we report that UNC45A is essential for breast cancer cell growth, but is dispensable for normal cell proliferation. Immunofluorescence microscopy, along with gene microarray and RT-quantitative PCR analyses, revealed that UNC45A localizes to the cancer cell nucleus, where it up-regulates the transcriptional activity of the glucocorticoid receptor and thereby promotes expression of the mitotic kinase NIMA-related kinase 7 (NEK7). We observed that UNC45A-deficient cancer cells exhibit extensive pericentrosomal material disorganization, as well as defects in centrosomal separation and mitotic chromosome alignment. Consequently, these cells stalled in metaphase and cytokinesis and ultimately underwent mitotic catastrophe, phenotypes that were rescued by heterologous NEK7 expression. Our results identify a key role for the co-chaperone UNC45A in cell proliferation and provide insight into the regulatory mechanism. We propose that UNC45A represents a promising new therapeutic target to inhibit cancer cell growth in solid tumor types.

Indexed as

Gene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticBreast NeoplasmsCarcinogenesisFemaleHeLa CellsHumansIntracellular Signaling Peptides and ProteinsMCF-7 CellsMitosisNeoplasm MetastasisNeoplasm ProteinsNIMA-Related KinasesPC-3 CellsIntracellular Signaling Peptides and ProteinsNEK7 protein, humanNeoplasm ProteinsNIMA-Related KinasesUNC45A protein, humancancer biologycentrosomeglucocorticoid receptorHeat shock protein 90Hsp90KEK7mitosismolecular chaperoneUNC-45AUNC45A

Identifiers

PMID30737284
PMCPMC6462532
OpenAlexW2912209648

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.