Evidence map›Paper›PMID 39920118›Full record

ArticleCell death discovery2025

Targeting MDM2 affects spastin protein levels and functions: implications for HSP treatment.

Francesca Sardina, Federica Polverino, Sonia Valentini, Claudia Carsetti, Elisabetta Falvo, Giada Tisci, Silvia Soddu, Fabiola Moretti, Alessandro Paiardini, Cinzia Rinaldo

Abstract read
In one paragraph

Article in Cell death discovery, 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. A GJA1 Variant Triggers Earlier SPG4 Onset by Destabilizing Deubiquitinase VCPIP1 to Lower SPASTIN Levels.Movement disorders : official journal of the Movement Disorder Society · 2026
    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

10 authors.

Francesca SardinaInstitute of Molecular Biology and Pathology, Italian National Research Council, c/o Sapienza University, Rome, Italy. francesca.sardina3@gmail.com.ORCID http://orcid.org/0000-0001-6474-2079
Federica PolverinoInstitute of Molecular Biology and Pathology, Italian National Research Council, c/o Sapienza University, Rome, Italy.
Sonia ValentiniInstitute of Biochemistry and Cell Biology, Italian National Research Council, Rome, Italy.
Claudia CarsettiInstitute of Molecular Biology and Pathology, Italian National Research Council, c/o Sapienza University, Rome, Italy.
Elisabetta FalvoInstitute of Molecular Biology and Pathology, Italian National Research Council, c/o Sapienza University, Rome, Italy.
Giada TisciInstitute of Molecular Biology and Pathology, Italian National Research Council, c/o Sapienza University, Rome, Italy.
Silvia SodduUnit of Cellular Networks and Molecular Therapeutic Targets, Department of Research and Advanced Technologies, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
Fabiola MorettiInstitute of Biochemistry and Cell Biology, Italian National Research Council, Rome, Italy.ORCID http://orcid.org/0000-0002-2691-1254
Alessandro PaiardiniDepartment of Biochemical Sciences "A. Rossi Fanelli", Sapienza University, Rome, Italy.ORCID http://orcid.org/0000-0001-9078-7545
Cinzia RinaldoInstitute of Molecular Biology and Pathology, Italian National Research Council, c/o Sapienza University, Rome, Italy. cinzia.rinaldo@uniroma1.it.ORCID http://orcid.org/0000-0001-6124-762X

Funding

AFM-Téléthon (French Muscular Dystrophy Association) 23786AFM-Téléthon (French Muscular Dystrophy Association) 24904Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research) 20447Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research) 218149Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research) 29699-2023Consiglio Nazionale delle Ricerche (National Research Council) DBA.AD005.225-NUTRAGE-FOE2021Fondazione Telethon (Telethon Foundation) GMR23T2157Fondazione Umberto Veronesi (Umberto Veronesi Foundation) n aMinistero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research) 2022-N3JXLAMinistero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research) #2022WC7BL2Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research) 2022WYCLTR
6 · The paper itself

Abstract

Spastin is a microtubule (MT) severing enzyme that regulates several cell functions associated with MT dynamics. A reduction in spastin protein levels is responsible for approximately 40% of cases of Hereditary Spastic Paraplegia (HSP), a neurodegenerative disease. Currently, there is no cure for HSP but strategies to induce a recovery of spastin levels are emerging as potential therapeutic approaches. Here, we show that MDM2 interacts with spastin MT-interacting and trafficking (MIT) domain. By biochemical and functional experiments, we demonstrate that MDM2 binds spastin and regulates its levels in a post-transcriptional manner independently of the E3 ubiquitin ligase activity. Of relevance, treatment of spastin-deficient cells with the MDM2 inhibitor Nutlin-3a can restore spastin levels and functions, such as cytokinetic abscission and sorting of transferrin receptor. These findings identify MDM2 as a novel interactor of spastin and a potential druggable regulator of its protein levels.

Identifiers

PMID39920118
PMCPMC11806007

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.