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

Autor:	de Luna Vitorino FN; Laboratório de Ciclo Celular - Center of Toxins, Immune-Response and Cell Signalling - CeTICS, Instituto Butantan, São Paulo, SP 055503-900, Brazil.; Programa de Pós-Graduação Interunidades em Biotecnologia, Universidade de São Paulo, São Paulo, SP 05508-000, Brazil., Levy MJ; Stowers Institute for Medical Research, Kansas City, MO 64110, USA., Mansano Wailemann RA; Laboratório de Ciclo Celular - Center of Toxins, Immune-Response and Cell Signalling - CeTICS, Instituto Butantan, São Paulo, SP 055503-900, Brazil., Lopes M; Laboratório de Ciclo Celular - Center of Toxins, Immune-Response and Cell Signalling - CeTICS, Instituto Butantan, São Paulo, SP 055503-900, Brazil., Silva ML; Laboratório de Ciclo Celular - Center of Toxins, Immune-Response and Cell Signalling - CeTICS, Instituto Butantan, São Paulo, SP 055503-900, Brazil., Sardiu ME; Stowers Institute for Medical Research, Kansas City, MO 64110, USA., Garcia BA; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA., Machado Motta MC; Laboratório de Ultraestrutura Celular Hertha Meyer, Centro de Pesquisa em Medicina de Precisão, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro-UFRJ, Rio de Janeiro, RJ 21491-590, Brazil.; Centro Nacional de Biologia Estrutural e Bioimagem, Rio de Janeiro, RJ 21941-902, Brazil., Oliveira CC; Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, SP 05508-000, Brazil., Armelin HA; Laboratório de Ciclo Celular - Center of Toxins, Immune-Response and Cell Signalling - CeTICS, Instituto Butantan, São Paulo, SP 055503-900, Brazil., Florens LA; Stowers Institute for Medical Research, Kansas City, MO 64110, USA., Washburn MP; Stowers Institute for Medical Research, Kansas City, MO 64110, USA., Pinheiro Chagas da Cunha J; Laboratório de Ciclo Celular - Center of Toxins, Immune-Response and Cell Signalling - CeTICS, Instituto Butantan, São Paulo, SP 055503-900, Brazil.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2023 Nov 15; Vol. 136 (22). Date of Electronic Publication: 2023 Nov 30.
DOI:	10.1242/jcs.260989
Abstrakt:	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 chromatin-remodeling proteins. The global transcriptional rate and nucleolus area increased along with nucleolar disorganization upon 24 h of FGF2 stimulation. FGF2 stimulation induced immature rRNA accumulation by increasing rRNA transcription. The rDNA-associated protein analysis reinforced that FGF2 stimulus interferes with transcription and rRNA processing. RNA Pol I inhibition partially reversed the growth arrest induced by FGF2, indicating that changes in rRNA expression might be crucial for triggering the antiproliferative effect. Taken together, we demonstrate that the antiproliferative FGF2 stimulus triggers significant transcriptional changes and modulates the main cell transcription site, the nucleolus. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2023. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu