Phosphoproteomic analysis of leukemic cells after RNA interference-mediated depletion of CDC25A

ABSTRACT: Molecular and functional networks driving coordination between cell cycle and mRNA translation remain to be explored. Here, we used mass spectrometry-based proteomics to comprehensively investigate the interactome and phosphoproteome of the cell cycle regulator CDC25A. This highlighted several actors of mRNA regulation, such as RNA-binding proteins and translation factors, as interacting partners of CDC25A. Ectopic overexpression of CDC25A increased global translation without affecting the cell cycle, while inhibiting CDC25 phosphatases rapidly decreased protein synthesis. A Cyclin Dependent Kinase (CDK) interaction-deficient mutant of CDC25A also enhanced translation, indicating a CDK-independent role. Our results revealed an interplay between CDC25A and CDC25B whereby down-regulation of CDC25A led to compensatory overexpression of CDC25B, while down-regulation of CDC25B was not compensated by CDC25A, reducing mRNA translation. Notably, the roles of CDC25A and CDC25B in mRNA translation are independent of the cell cycle, with CDC25A regulating elongation and CDC25B rather involved into initiation. Finally, we confirmed the implication of CDC25A in translation in acute myeloid leukemia cell lines, in which RNA interference-mediated depletion of CDC25A inhibited translation. Altogether, we propose that CDC25 phosphatases can be considered as signaling platforms coordinating cell cycle progression with mRNA translation and protein synthesis.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Myeloid Cell

DISEASE(S): Acute Myeloid Leukemia

SUBMITTER: Emilie-Fleur GAUTIER  

LAB HEAD: Stéphane Manenti

PROVIDER: PXD066447 | Pride | 2026-07-15

REPOSITORIES: Pride