Evidence map›Paper›PMID 40838616›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2025

MKLN1-dependent GID4/CTLH E3 ubiquitin ligase complex assemblies are required to support B-cell antibody diversification.

Philip Barbulescu, Matthew K Wong, Leon Baronian, Pengyu Wang, Abdulmateen Aderinto, Matthias Kneussel, Alberto Martin

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Spotlight onGenes · 2025
    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

7 authors.

Philip BarbulescuDepartment of Immunology, University of Toronto, Toronto, ON, Canada.
Matthew K WongDepartment of Immunology, University of Toronto, Toronto, ON, Canada.
Leon BaronianDepartment of Immunology, University of Toronto, Toronto, ON, Canada.
Pengyu WangDepartment of Immunology, University of Toronto, Toronto, ON, Canada.
Abdulmateen AderintoDepartment of Immunology, University of Toronto, Toronto, ON, Canada.
Matthias KneusselDepartment of Molecular Neurogenetics, Zentrum für Molekulare Neurobiologie Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Alberto MartinDepartment of Immunology, University of Toronto, Toronto, ON, Canada.

Funding

CIHR PJT-153307CIHR PJT-156330Deutsche Forschungsgemeinschaft KN556/18-1Ontario Graduate Student ScholarshipQueen Elizabeth II Graduate Scholarship in Science and Technology
6 · The paper itself

Abstract

C-terminal to LisH (CTLH) E3 ubiquitin ligase complexes regulate a broad range of biological processes and forms separate supramolecular CTLH-MKLN1 and CTLH-WDR26 assemblies possessing distinct substrate specificities. Our previous work revealed that the CTLH complex utilizes the FAM72A substrate adaptor to ubiquitinate and degrade the uracil-DNA glycosylase 2 (UNG2) base excision repair factor. This outcome in B cells permits deoxyuridine mutations catalyzed by activation-induced cytidine deaminase (AID) to persist toward mutational outcomes and drive antibody diversification events. Here, we report that Mkln1-/- mice specifically lacking assembly of CTLH-MKLN1 complexes display reduced somatic hypermutation and class switch recombination frequencies due to increased UNG2, similar to Fam72a-/- mice. Strikingly, Mkln1-/- mice showed increased germinal center B cells and defects during B-cell development, a phenotype not observed in Fam72a-/- mice, suggesting that MKLN1 regulates proteins that are independent of FAM72A. Together, this work identifies that CTLH-MKLN1 ubiquitin E3 ligase complexes are critical in generating effective humoral immune responses and reveals distinctions between FAM72A-dependent and -independent CTLH complex modalities.

Indexed as

Antibody DiversityB-LymphocytesUbiquitin-Protein LigasesAnimalsGerminal CenterImmunoglobulin Class SwitchingMiceMice, Inbred C57BLMice, KnockoutSomatic Hypermutation, ImmunoglobulinUbiquitin-Protein LigasesB cellsclass switch recombinationC-terminal to LisHsomatic hypermutationUNG2

Identifiers

PMID40838616
PMCPMC12576123

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.