Evidence map›Paper›PMID 36114006›Full record

ArticleLife science alliance2022

ALS-linked loss of Cyclin-F function affects HSP90.

Alexander Siebert, Vanessa Gattringer, Jochen H Weishaupt, Christian Behrends

Open access · goldAbstract read
In one paragraph

Article in Life science alliance, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.1field-weighted citation impact, top 23% of its field
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

10 citing papers in PubMed, 14 citations in OpenAlex.

  1. ALS-FTD-linked CCNFJournal of neuroinflammation · 2026
    Article
  2. Article
  3. Article
  4. Structural mechanism for the recognition of E2F1 by the ubiquitin ligase adaptor Cyclin F.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. SKP1-CUL1-F-box: Key molecular targets affecting disease progression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Review
  6. Review
  7. Molecular Mechanisms of Medicinal PlantCurrent pharmaceutical design · 2024
    Article
  8. Review
  9. Article
  10. Review
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

4 authors at 2 institutions in 1 country.

Alexander SiebertMunich Cluster for Systems Neurology (SyNergy), Medical Faculty, Ludwig-Maximilians-University München, Munich, Germany.
Vanessa GattringerMunich Cluster for Systems Neurology (SyNergy), Medical Faculty, Ludwig-Maximilians-University München, Munich, Germany.
Jochen H WeishauptDivision of Neurodegenerative Disorders, Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neurosciences, Heidelberg University, Mannheim, Germany.
Christian BehrendsMunich Cluster for Systems Neurology (SyNergy), Medical Faculty, Ludwig-Maximilians-University München, Munich, Germany christian.behrends@mail03.med.uni-muenchen.de.ORCID 0000-0002-9184-7607
Munich Cluster for Systems Neurology · DEHeidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The founding member of the F-box protein family, Cyclin-F, serves as a substrate adaptor for the E3 ligase Skp1-Cul1-F-box (SCF)<sup>Cyclin-F</sup> which is responsible for ubiquitination of proteins involved in cell cycle progression, DNA damage and mitotic fidelity. Missense mutations in <i>CCNF</i> encoding for Cyclin-F are associated with amyotrophic lateral sclerosis (ALS). However, it remains elusive whether <i>CCNF</i> mutations affect the substrate adaptor function of Cyclin-F and whether altered SCF<sup>Cyclin-F</sup>-mediated ubiquitination contributes to pathogenesis in <i>CCNF</i> mutation carriers. To address these questions, we set out to identify new SCF<sup>Cyclin-F</sup> targets in neuronal and ALS patient-derived cells. Mass spectrometry-based ubiquitinome profiling of <i>CCNF</i> knockout and mutant cell lines as well as Cyclin-F proximity and interaction proteomics converged on the HSP90 chaperone machinery as new substrate candidate. Biochemical analyses provided evidence for a Cyclin-F-dependent association and ubiquitination of HSP90AB1 and implied a regulatory role that could affect the binding of a number of HSP90 clients and co-factors. Together, our results point to a possible Cyclin-F loss-of-function-mediated chaperone dysregulation that might be relevant for ALS.

Indexed as

Amyotrophic Lateral SclerosisCyclinsF-Box ProteinsHSP90 Heat-Shock ProteinsHumansUbiquitinationUbiquitin-Protein LigasesCCNF protein, humanCyclinsF-Box ProteinsHSP90 Heat-Shock ProteinsUbiquitin-Protein Ligases

Identifiers

PMID36114006
PMCPMC9481933
OpenAlexW4296078746

What OpenQuestion holds

Textmetadata
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.