MassIVE MSV000090518

Partial Public PXD037339

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

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Description

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. [doi:10.25345/C5BC3T23T] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Proteomics, Chromatin, Nucleolus, FGF2, Transcription

Contact

Principal Investigators:
(in alphabetical order) 		Julia Pinheiro Chagas da Cunha, Butantan Institute, Brazil
Submitting User: francisca_vitorino

Publications

de Luna Vitorino FN, Levy MJ, Mansano Wailemann RA, Lopes M, Silva ML, Sardiu ME, Garcia BA, Motta MCM, Oliveira CC, Armelin HA, Florens LA, Washburn MP, da Cunha JPC.
FGF2 antiproliferative effect in K-ras-driven tumor cells involves modulation of rRNA and nucleolus.
J Cell Sci. Epub 2023 Nov 3.

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