Evidence map›Paper›PMID 38099650›Full record

ArticleeLife2023

Distinct states of nucleolar stress induced by anticancer drugs.

Tamara A Potapova, Jay R Unruh, Juliana Conkright-Fincham, Charles A S Banks, Laurence Florens, David Alan Schneider, Jennifer L Gerton

Open access · goldAbstract read
In one paragraph

Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
8.2field-weighted citation impact, top 2% 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

34 citing papers in PubMed, 53 citations in OpenAlex.

  1. Article
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  4. Review
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  12. eLife · 2026
    Article
  13. Article
  14. bioRxiv : the preprint server for biology · 2026
    Article
  15. Article
  16. Mechanobiology of the Nucleolus.Biology of the cell · 2026
    Review
  17. Article
  18. Article
  19. Review
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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

7 authors at 1 institution in 1 country.

Tamara A PotapovaStowers Institute for Medical Research, Kansas City, United States.ORCID 0000-0003-2761-1795
Jay R UnruhStowers Institute for Medical Research, Kansas City, United States.ORCID 0000-0003-3077-4990
Juliana Conkright-FinchamStowers Institute for Medical Research, Kansas City, United States.
Charles A S BanksStowers Institute for Medical Research, Kansas City, United States.
Laurence FlorensStowers Institute for Medical Research, Kansas City, United States.ORCID 0000-0002-9310-6650
David Alan SchneiderDepartment of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, United States.ORCID 0000-0003-0635-5091
Jennifer L GertonStowers Institute for Medical Research, Kansas City, United States.ORCID 0000-0003-0743-3637
Stowers Institute for Medical Research · US

Funding

UNDERSTANDING THE ROLES OF RNA POLYMERASE I IN TRANSCRIPTION AND BEYONDR35GM140710 · NIGMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SCHNEIDER, DAVID ALAN · 2021 to 2025
$2.1M
NIGMS NIH HHS R35 GM140710
6 · The paper itself

Abstract

Ribosome biogenesis is a vital and highly energy-consuming cellular function occurring primarily in the nucleolus. Cancer cells have an elevated demand for ribosomes to sustain continuous proliferation. This study evaluated the impact of existing anticancer drugs on the nucleolus by screening a library of anticancer compounds for drugs that induce nucleolar stress. For a readout, a novel parameter termed 'nucleolar normality score' was developed that measures the ratio of the fibrillar center and granular component proteins in the nucleolus and nucleoplasm. Multiple classes of drugs were found to induce nucleolar stress, including DNA intercalators, inhibitors of mTOR/PI3K, heat shock proteins, proteasome, and cyclin-dependent kinases (CDKs). Each class of drugs induced morphologically and molecularly distinct states of nucleolar stress accompanied by changes in nucleolar biophysical properties. In-depth characterization focused on the nucleolar stress induced by inhibition of transcriptional CDKs, particularly CDK9, the main CDK that regulates RNA Pol II. Multiple CDK substrates were identified in the nucleolus, including RNA Pol I- recruiting protein Treacle, which was phosphorylated by CDK9 in vitro. These results revealed a concerted regulation of RNA Pol I and Pol II by transcriptional CDKs. Our findings exposed many classes of chemotherapy compounds that are capable of inducing nucleolar stress, and we recommend considering this in anticancer drug development.

Indexed as

Antineoplastic AgentsCell NucleolusCell NucleusCyclin-Dependent KinasesRibosomesRNARNA Polymerase IRNA Polymerase IIAntineoplastic AgentsCyclin-Dependent KinasesRNARNA Polymerase IRNA Polymerase IIanticancer drugscancer biologyCDK9cell biologyhumannucleolusRNA Pol ITCOF1/Treacle

Identifiers

PMID38099650
PMCPMC10723795
OpenAlexW4384343056

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.