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FGF2 antiproliferative stimulus triggers proteomic and transcriptional changes associated with nucleolar disorganization in K-ras-driven mouse tumor cells (CLASP MudPIT data)

ABSTRACT: Chromatin plays a crucial role in the intermediation between cell signaling and gene expression. The nucleolus is sensitive to stress and can orchestrate a chain of cellular events in response to stress signals. Despite being a growth factor, FGF2 has anti-proliferative and tumor-suppressive functions in some cellular contexts. In this work, we investigated how the antiproliferative effect of FGF2 modulates chromatin, nucleolus, and rDNA-associated proteins. The chromatin and nucleolar proteome indicated that FGF2 stimulation modulates proteins related to transcription regulation, particularly rRNA expression, and chromatin remodeling proteins. Upon 24 hrs of FGF2 stimulation, the global transcriptional rate and nucleolus area increased in associationalong with intense nucleolar disorganization detected by fibrillarin dispersion and electron microscopy analyses. We confirmed that FGF2 stimulation induced immature rRNA accumulation by increasing rRNA transcription regardless of changes in ribosome profiling. The rDNA-associated protein analysis reinforced that FGF2 stimulus interferes with transcription and rRNA processing/modification, since the proteins Nolc1 and Tcof1 are were upregulated after FGF2 stimulation. Changes in rRNA expression may be crucial for triggering the antiproliferative effect induced by FGF2 since inhibiting RNA Pol I, responsible for rRNA expression, partially reversed the growth arrest induced by FGF2. Taken together, we demonstrate that the antiproliferative FGF2 stimulus triggers significant transcriptional changes, and modulation modulates of the main cell transcription site, the nucleolus, directly modulating the proteome of the rDNA loci.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Julia Pinheiro Chagas da Cunha

PROVIDER: MSV000090516 | MassIVE | Wed Oct 12 07:57:00 BST 2022

SECONDARY ACCESSION(S): PXD037310

REPOSITORIES: MassIVE

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The antiproliferative effect of FGF2 in K-Ras-driven tumor cells involves modulation of rRNA and the nucleolus.

de Luna Vitorino Francisca N FN Levy Michaella J MJ Mansano Wailemann Rosangela A RA Lopes Mariana M Silva Mariana Loterio ML Sardiu Mihaela E ME Garcia Benjamin A BA Machado Motta Maria Cristina MC Oliveira Carla Columbano CC Armelin Hugo Aguirre HA Florens Laurence A LA Washburn Michael P MP Pinheiro Chagas da Cunha Julia J

Journal of cell science 20231130 22

The nucleolus is sensitive to stress and can orchestrate a chain of cellular events in response to stress signals. Despite being a growth factor, FGF2 has antiproliferative and tumor-suppressive functions in some cellular contexts. In this work, we investigated how the antiproliferative effect of FGF2 modulates chromatin-, nucleolus- and rDNA-associated proteins. The chromatin and nucleolar proteome indicated that FGF2 stimulation modulates proteins related to transcription, rRNA expression and ...[more]

PMID: 37921359

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