Evidence map›Paper›PMID 40530693›Full record

ArticleNucleic acids research2025

HIV Vpr activates a nucleolar-specific ATR pathway to degrade the nucleolar stress sensor CCDC137.

Karly A Nisson, Rishi S Patel, Yennifer Delgado, Mehdi Bouhaddou, Lucie Etienne, Oliver I Fregoso

Abstract read
In one paragraph

Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

6 authors.

Karly A NissonMolecular Biology Institute, University of California, Los Angeles, CA, 90095, United States.
Rishi S PatelDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, 90095, United States.
Yennifer DelgadoMolecular Biology Institute, University of California, Los Angeles, CA, 90095, United States.
Mehdi BouhaddouMolecular Biology Institute, University of California, Los Angeles, CA, 90095, United States.
Lucie EtienneCentre International de Recherche en Infectiologie (CIRI), Inserm U1111, UCBL1, CNRS UMR5308, ENS de Lyon, Université de Lyon, Lyon, 69007, France.ORCID 0000-0002-8585-7534
Oliver I FregosoMolecular Biology Institute, University of California, Los Angeles, CA, 90095, United States.ORCID 0000-0003-3087-3374

Funding

Project 3U54AI170792 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Alexander Marson · 2022 to 2026
$35.7M
MULTIDISCIPLINARY TRAINING IN MICROBIAL PATHOGENESIST32AI007323 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Peter John Bradley · 1988 to 2026
$8.6M
Defining the regulation of double-strand DNA break repair by HIV VprR01AI147837 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FREGOSO, OLIVER I · 2019 to 2023
$1.9M
French Research Agency on HIV and Emerging Infectious Diseases ANRS/MIE ECTZ19143HIV Accessory and Regulatory Complexes (HARC) Collaborative Development Award U54AI170792NIAID NIH HHS R01 AI147837NIAID NIH HHS T32 AI007323NIAID NIH HHS U54 AI170792NIH HHS R01AI147837NIH HHS T32AI007323UCLA-CDU Center for AIDS ResearchW.M. Keck Foundation Award
6 · The paper itself

Abstract

The lentiviral accessory protein Vpr engages an extensive network of cellular pathways to drive diverse host consequences. Of its many phenotypes, CRL4A-E3 ubiquitin ligase complex co-option, DNA damage response (DDR) engagement, and G2/M arrest are conserved and thus proposed to be functionally important. How Vpr effects these functions and whether they explain how Vpr dysregulates additional cellular pathways remain unclear. Here we leverage the ability of Vpr to deplete the nucleolar protein CCDC137 to understand how Vpr-induced DDR activation impacts nucleolar processes. We characterize CCDC137 as an indirect Vpr target whose degradation does not correlate with Vpr-induced G2/M arrest. Yet, degradation is conserved among Vpr from the pandemic HIV-1 and related SIVcpz/SIVgor, and it is triggered by genomic insults that activate a nucleolar ATR pathway in a manner similar to camptothecin. We determine that Vpr causes ATR-dependent features of nucleolar stress that correlate with CCDC137 degradation, including redistribution of nucleolar proteins, altered nucleolar morphology, and repressed ribosome biogenesis. Together, these data distinguish CCDC137 as a non-canonical Vpr target that may serve as a sensor of nucleolar disruption, and in doing so, identify a novel role for Vpr in nucleolar stress.

Indexed as

Ataxia Telangiectasia Mutated ProteinsCell NucleolusNuclear Proteinsvpr Gene Products, Human Immunodeficiency VirusDNA DamageG2 Phase Cell Cycle CheckpointsHEK293 CellsHeLa CellsHIV-1HumansProteolysisSignal TransductionAtaxia Telangiectasia Mutated ProteinsATR protein, humanNuclear Proteinsvpr Gene Products, Human Immunodeficiency Virusvpr protein, Human immunodeficiency virus 1

Identifiers

PMID40530693
PMCPMC12203918

What Socratic 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 Socratic graph.