Novel CDK-independent function of CDC25 phosphatases in mRNA translation
Abstract
Molecular and functional networks driving coordination between cell cycle and mRNA translation remain to be explored. Here, we use mass spectrometry-based proteomics to comprehensively investigate the interactome and phosphoproteome of the cell cycle regulator CDC25A. We identify actors of mRNA regulation, such as RNA-binding proteins and translation factors, as interacting partners of CDC25A. CDC25A overexpression increases global translation, whereas catalytic inactivation or pharmacological inhibition decreases protein synthesis. A Cyclin-Dependent Kinase (CDK) interaction-deficient mutant of CDC25A also enhances translation, indicating a CDK-independent role. Our results further reveal an interplay between CDC25A and CDC25B whereby downregulation of CDC25A leads to compensatory overexpression of CDC25B. The roles of CDC25A and CDC25B in mRNA translation are independent of their roles in the cell cycle, with CDC25A possibly regulating translation elongation and CDC25B rather involved in initiation. In acute myeloid leukemia cells, CDC25A depletion also inhibits translation, suggesting its potential relevance as a therapeutic target. We propose that CDC25 phosphatases might be signaling platforms coordinating cell cycle progression with protein synthesis.
Related
- A novel class of conserved sucrose-phosphate phosphatases highlights the diversity of cyanobacterial sucrose metabolism
- Cap-Independent Translation Regulation of VEGF Using CRISPR-dCas13d
- Novel post-transcriptional dimension of glucocorticoid action through mRNA translation and P-body remodeling
- Structural basis of TACO1 function in mitochondrial translation elongation
- Investigating the effect of glucosamine conjugation on the inhibitory activity of 2,3-dihydro-1H-perimidine derivatives against protein tyrosine phosphatases
BibTeX
@article{shin2026novel,
title = {{Novel CDK-independent function of CDC25 phosphatases in mRNA translation}},
author = {Sauyeun Shin and Marie Cargnello and Lisa Pinchedé and Claire Medale Giamarchi and Cléa Villette and Alexandre Gay and Virginie Salnot and Emilie-Fleur Gautier and Erik Dassi and Stefania Millevoi and Anne Cammas and Stéphane Manenti},
journal = {EMBO Reports},
year = {2026},
month = jul,
doi = {10.1038/s44319-026-00852-y},
url = {https://hal.science/hal-05760789v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Novel CDK-independent function of CDC25 phosphatases in mRNA translation
AU - Sauyeun Shin
AU - Marie Cargnello
AU - Lisa Pinchedé
AU - Claire Medale Giamarchi
AU - Cléa Villette
AU - Alexandre Gay
AU - Virginie Salnot
AU - Emilie-Fleur Gautier
AU - Erik Dassi
AU - Stefania Millevoi
AU - Anne Cammas
AU - Stéphane Manenti
PY - 2026
DA - 2026/07/14
JO - EMBO Reports
DO - 10.1038/s44319-026-00852-y
UR - https://hal.science/hal-05760789v1
AB - Molecular and functional networks driving coordination between cell cycle and mRNA translation remain to be explored. Here, we use mass spectrometry-based proteomics to comprehensively investigate the interactome and phosphoproteome of the cell cycle regulator CDC25A. We identify actors of mRNA regulation, such as RNA-binding proteins and translation factors, as interacting partners of CDC25A. CDC25A overexpression increases global translation, whereas catalytic inactivation or pharmacological inhibition decreases protein synthesis. A Cyclin-Dependent Kinase (CDK) interaction-deficient mutant of CDC25A also enhances translation, indicating a CDK-independent role. Our results further reveal an interplay between CDC25A and CDC25B whereby downregulation of CDC25A leads to compensatory overexpression of CDC25B. The roles of CDC25A and CDC25B in mRNA translation are independent of their roles in the cell cycle, with CDC25A possibly regulating translation elongation and CDC25B rather involved in initiation. In acute myeloid leukemia cells, CDC25A depletion also inhibits translation, suggesting its potential relevance as a therapeutic target. We propose that CDC25 phosphatases might be signaling platforms coordinating cell cycle progression with protein synthesis.
SN - 1469-221X
SN - 1469-3178
ER -