Evidence map›Paper›PMID 41554709›Full record

ArticleNature communications2026

Guardian ubiquitin E3 ligases target cancer-associated APOBEC3 deaminases for degradation to promote human genome integrity.

Irene Schwartz, Valentina Budroni, Mathilde Meyenberg, Zuzana Hodakova, Harald Hornegger, Kathrin Hacker, Siegfried Schwartz, Daniel B Grabarczyk, Julian F Ehrmann, Sara Scinicariello and 5 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. 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

15 authors.

Irene Schwartz *Max Perutz Labs, Vienna BioCenter Campus (VBC), Dr. -Bohrgasse 9, Vienna, Austria.
Valentina Budroni *Max Perutz Labs, Vienna BioCenter Campus (VBC), Dr. -Bohrgasse 9, Vienna, Austria.ORCID http://orcid.org/0000-0002-6606-2031
Mathilde MeyenbergMax Perutz Labs, Vienna BioCenter Campus (VBC), Dr. -Bohrgasse 9, Vienna, Austria.
Zuzana HodakovaResearch Institute of Molecular Pathology (IMP), Vienna BioCenter Campus (VBC), Vienna, Austria.ORCID http://orcid.org/0000-0002-2599-0333
Harald HorneggerMax Perutz Labs, Vienna BioCenter Campus (VBC), Dr. -Bohrgasse 9, Vienna, Austria.
Kathrin HackerMax Perutz Labs, Vienna BioCenter Campus (VBC), Dr. -Bohrgasse 9, Vienna, Austria.
Siegfried SchwartzTU Wien, Faculty of Informatics, Vienna, Austria.
Daniel B GrabarczykResearch Institute of Molecular Pathology (IMP), Vienna BioCenter Campus (VBC), Vienna, Austria.ORCID http://orcid.org/0000-0003-0216-7085
Julian F EhrmannVienna Biocenter PhD Program, a Doctoral School of the University of Vienna and the Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0003-2518-5681
Sara ScinicarielloMax Perutz Labs, Vienna BioCenter Campus (VBC), Dr. -Bohrgasse 9, Vienna, Austria.
David HaselbachResearch Institute of Molecular Pathology (IMP), Vienna BioCenter Campus (VBC), Vienna, Austria.ORCID http://orcid.org/0000-0002-5276-5633
Jörg MencheMax Perutz Labs, Vienna BioCenter Campus (VBC), Dr. -Bohrgasse 9, Vienna, Austria.ORCID http://orcid.org/0000-0002-1583-6404
Tim ClausenResearch Institute of Molecular Pathology (IMP), Vienna BioCenter Campus (VBC), Vienna, Austria.ORCID http://orcid.org/0000-0003-1582-6924
G Elif KaragözMax Perutz Labs, Vienna BioCenter Campus (VBC), Dr. -Bohrgasse 9, Vienna, Austria.
Gijs A VersteegMax Perutz Labs, Vienna BioCenter Campus (VBC), Dr. -Bohrgasse 9, Vienna, Austria. gijs.versteeg@univie.ac.at.ORCID http://orcid.org/0000-0002-6150-2165

Funding

Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) 10.55776/F79Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) 10.55776/P36945Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) 10.55776/W1261
6 · The paper itself

Abstract

APOBEC family members play crucial roles in antiviral restriction. However, certain APOBEC3 (A3) proteins drive harmful hypermutation in humans, contributing to cancer. The cancer-associated A3 proteins are capable of transiting from the cytosol to the nucleus, where they can cause genome mutations. Here, we uncover a specific set of cellular pathways that protect genomic DNA from the major cancer-associated A3 proteins. Through genetic and proteomic screening, we identify UBR4, UBR5, and HUWE1 as key ubiquitin E3 ligases marking cancer-associated A3B and A3H-I for degradation, thereby limiting A3-driven hypermutation. Mechanistically, UBR5 and HUWE1 recognize A3s in the absence of their RNA binding partner, thus promoting proteasomal degradation of APOBEC3 protein that is not engaged in its antiviral cellular function. Depletion or mutation of the E3 ligases in cells and human cancer samples increases A3-driven genome mutagenesis. Our findings reveal that UBR4, UBR5, and HUWE1 are crucial factors in a ubiquitination cascade that maintains human genome stability.

Indexed as

Cytidine DeaminaseGenome, HumanGenomic InstabilityNeoplasmsTumor Suppressor ProteinsUbiquitin-Protein LigasesAPOBEC DeaminasesCell Line, TumorHEK293 CellsHumansMutationProteolysisUbiquitinationAPOBEC3 proteins, humanAPOBEC DeaminasesCytidine DeaminaseHUWE1 protein, humanTumor Suppressor ProteinsUbiquitin-Protein LigasesUBR5 protein, human

Identifiers

PMID41554709
PMCPMC12913773

What Socratic 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 Socratic graph.