Evidence map›Paper›PMID 42214329›Full record

ArticleMolecular cell2026

Mechanism of RACK1-dependent ZAKα activation at stalled and collided ribosomes.

Anna Constance Vind, José Francisco Martínez, Zhenzhen Wu, Andrii Bugai, Kelly Mordente, Giancarlo Abis, Sébastien Chamois, Sofia Ramalho, Catarina Pechincha, Laura Ryder and 11 more

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In one paragraph

Article in Molecular cell, 2026. 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. Review
  2. 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

21 authors.

Anna Constance VindCenter for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.
José Francisco MartínezCenter for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.
Zhenzhen WuCenter for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.
Andrii BugaiDepartment of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
Kelly MordenteCenter for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.
Giancarlo AbisRandall Centre for Cell and Molecular Biophysics, King's College London, London SE1 1UL, UK.
Sébastien ChamoisCenter for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland.
Sofia RamalhoCenter for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.
Catarina PechinchaCenter for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.
Laura RyderCenter for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.
Qiuyan ChenCenter for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.
Mads RasmussenCenter for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.
Xinyao ShiCenter for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.
Dandan HeCenter for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.
Jesper Q SvejstrupCenter for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.
Peter HaahrCenter for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.
David GatfieldCenter for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland.
Maria R ConteRandall Centre for Cell and Molecular Biophysics, King's College London, London SE1 1UL, UK.
Torben Heick JensenDepartment of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
Melanie BlasiusCenter for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.
Simon Bekker-JensenCenter for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark. Electronic address: sbj@sund.ku.dk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite a growing interest in the ribotoxic stress response (RSR), it remains unknown how the upstream p38- and JNK-activating MAP3 kinase ZAKα senses translational impairment. Combining AlphaFold3 prediction and RNA crosslinking and immunoprecipitation (CLIP), we uncover that ZAKα dynamically monitors the mRNA exit channel of elongating ribosomes. This is accomplished by ZAKα via direct interactions with the ribosomal proteins RACK1 and RPS27 as well as 18S rRNA helix-26. In this conformation, the RNA-binding S (sensing) and C-terminal domain of ZAKα span across the mRNA exit channel. Loss of ribosome processivity and mRNA stasis stabilizes the interaction allowing for kinase activation. Prolonged binding of ZAKα to stalled and collided ribosomes is associated with sequestration of the sterile alpha-motif (SAM) domain on RACK1, which allows for transient ZAKα dimerization, activation loop trans-autophosphorylation, and RSR activation. Our findings highlight how ZAKα senses both stalled and collided ribosomes in human cells through overlapping mechanisms.

Indexed as

Neoplasm ProteinsReceptors for Activated C KinaseRibosomesEnzyme ActivationHEK293 CellsHeLa CellsHumansPhosphorylationProtein BindingProtein BiosynthesisRibosomal ProteinsRNA, MessengerNeoplasm ProteinsRACK1 protein, humanReceptors for Activated C KinaseRibosomal ProteinsRNA, Messengerribosome collisionribosome stallingribotoxic stress responsetranslation surveillanceZAK-alpha

Identifiers

PMID42214329
PMCPMC13293227

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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.