Evidence map›Paper›PMID 41053424›Full record

ArticleCommunications biology2025

NAA60 facilitates LRRC8A- and LRRC8D-mediated platinum drug uptake.

Carmen Alexandra Widmer, Anna Moyseos, Ismar Klebic, Martina Dettwiler, Martín González-Fernández, Ewa Gogola, Myriam Siffert, Natasha Buchs, Sophie Braga-Lagache, Anne-Christine Uldry and 3 more

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In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

13 authors.

Carmen Alexandra WidmerInstitute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.ORCID http://orcid.org/0000-0001-7030-4550
Anna MoyseosInstitute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Ismar KlebicInstitute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Martina DettwilerInstitute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Martín González-FernándezInstitute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.ORCID http://orcid.org/0009-0006-8308-5493
Ewa GogolaDivision of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Myriam SiffertInstitute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Natasha BuchsProteomics and Mass Spectrometry Core Facility, Department for Biomedical Research (DBMR), University of Bern, Bern, Switzerland.
Sophie Braga-LagacheProteomics and Mass Spectrometry Core Facility, Department for Biomedical Research (DBMR), University of Bern, Bern, Switzerland.
Anne-Christine UldryProteomics and Mass Spectrometry Core Facility, Department for Biomedical Research (DBMR), University of Bern, Bern, Switzerland.
Jos JonkersDivision of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-9264-9792
Manfred HellerProteomics and Mass Spectrometry Core Facility, Department for Biomedical Research (DBMR), University of Bern, Bern, Switzerland.ORCID http://orcid.org/0000-0002-6364-7325
Sven RottenbergInstitute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland. sven.rottenberg@unibe.ch.ORCID http://orcid.org/0000-0003-2044-9844

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) 320030M_219453
6 · The paper itself

Abstract

The platinum-based drugs cis- and carboplatin, which are crucial for treating cancers with DNA repair defects, like those caused by BRCA1/2 mutations, rely on the volume-regulated anion channel subunits LRRC8A and LRRC8D for about 50% of cellular drug uptake. Yet, the precise mechanisms of how LRRC8A and LRRC8D mediate this function are largely unknown. Here, we identify NAA60, an N-terminal acetyltransferase, which localizes to the Golgi apparatus to affect LRRC8A and LRRC8D function. Our data suggest that NAA60 acetylates the LRRC8A/D N-termini, and its loss decreases cis- and carboplatin uptake resulting in drug resistance of otherwise hypersensitive BRCA1;p53-deficient cells and tumors. Furthermore, we mimicked the absence of the neutralizing acetyl moiety that is observed after loss of NAA60 by introducing positively charged amino acids at the N-termini of LRRC8A/D, which indeed decreased cis- and carboplatin sensitivity. Our findings highlight the importance of N-terminal acetylation by NAA60 for effective platinum drug uptake, offering new insights into overcoming drug resistance.

Indexed as

AcetyltransferasesAntineoplastic AgentsCarboplatinMembrane ProteinsAcetylationAnimalsCell Line, TumorCisplatinDrug Resistance, NeoplasmHumansMiceAcetyltransferasesAntineoplastic AgentsCarboplatinCisplatinMembrane Proteins

Identifiers

PMID41053424
PMCPMC12501270

What OpenQuestion holds

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Registered trials

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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.