Evidence map›Paper›PMID 42228561›Full record

ArticleCell reports2026

Faf1 accelerates p97-mediated protein unfolding by promoting ubiquitin engagement.

Zengwei Liao, Connor Arkinson, Andreas Martin

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
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  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors.

Zengwei LiaoCalifornia Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Connor ArkinsonCalifornia Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Andreas MartinCalifornia Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: a.martin@berkeley.edu.

Funding

ATP-Dependent Protein Unfolding and Translocation by the Eukaryotic ProteasomeR01GM094497 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI MARTIN, ANDREAS · 2011 to 2024
$3.7M
NIGMS NIH HHS R01 GM094497
6 · The paper itself

Abstract

P97/VCP is a protein unfoldase of the AAA+ ATPase family that plays essential roles in numerous processes, including ER-associated degradation and DNA replication. For unfolding of proteins modified with K48-linked ubiquitin chains, p97 works with the heterodimeric cofactor Ufd1-Npl4, and the cofactor Faf1 was shown to enhance this activity during replisome disassembly by unknown mechanisms. Here, we employ an in vitro reconstituted system with human components for biochemical experiments, FRET-based assays, and cryo-EM structure determination to reveal that Faf1 generally accelerates ubiquitin-dependent substrate processing by promoting the unfolding of an initiator ubiquitin and its engagement by the ATPase. Faf1 thereby uses its p97-bound C-terminal UBX domain to anchor a long helix that braces Ufd1's UT3 domain and stabilizes Ufd1-Npl4 for ubiquitin unfolding. Our findings demonstrate how p97 works simultaneously with several cofactors to facilitate the unfolding of ubiquitinated proteins, indicating more complex regulatory mechanisms than for the simpler yeast Cdc48.

Indexed as

Adaptor Proteins, Signal TransducingAdenosine TriphosphatasesProtein UnfoldingUbiquitinValosin Containing ProteinApoptosis Regulatory ProteinsHumansIntracellular Signaling Peptides and ProteinsNuclear ProteinsProtein BindingProtein DomainsAdaptor Proteins, Signal TransducingAdenosine TriphosphatasesApoptosis Regulatory ProteinsFAF1 protein, humanIntracellular Signaling Peptides and ProteinsNPLOC4 protein, humanNuclear Proteinsp97 ATPaseUbiquitinUFD1 protein, humanValosin Containing ProteinCP: Molecular biologyFaf1Faf2initiator ubiquitinp97ubiquitin-dependent protein unfoldingUfd1/Npl4

Identifiers

PMID42228561
PMCPMC13356908

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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.