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

Author(s):Show less -

Vitorino, Francisca N. de Luna ; Levy, Michaella J. ; Wailemann, Rosangela A. Mansano ; Lopes, Mariana ; Silva, Mariana Loterio ; Sardiu, Mihaela E. ; Garcia, Benjamin A. ; Motta, Maria Cristina Machado ; Oliveira, Carla Columbano ; Armelin, Hugo Aguirre ; Florens, Laurence A. ; Washburn, Michael P. ; da Cunha, Julia Pinheiro Chagas

• Document type: Journal article
• Source: Journal of Cell Science; v. 136, n. 22, p. 13-pg., 2023-11-01.

Abstract

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 chromatinremodeling 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 rDNAassociated 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. (AU)

• FAPESP's process: 17/18344-9 - Quantitative chromatin proteomics upon FGF2 treatment: analysis of transcriptional regulation and involvement of cdc42
• Grantee: Francisca Nathália de Luna Vitorino
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 11/22619-7 - Nuclei and chromatin alterations through cell cycle and senescence in mammalian cells
• Grantee: Julia Pinheiro Chagas da Cunha
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 17/06104-3 - Functional analysis of Trypanosoma Cruzi histone H2B variant
• Grantee: Julia Pinheiro Chagas da Cunha
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/15553-9 - Going deeper into Trypanosoma cruzi chromatin regulation: identifying new players and quizzing its impact on a potential transcription control
• Grantee: Julia Pinheiro Chagas da Cunha
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 19/17675-7 - DCas9-targeted rDNA loci-specific protein isolation of tumor cells stimulated with FGF2
• Grantee: Francisca Nathália de Luna Vitorino
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)