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1.
Biochem Biophys Res Commun ; 495(1): 846-853, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29158086

RESUMO

Retinoic acid receptors (RARs) are classically considered as nuclear ligand-dependent regulators of transcription. Here we highlighted a novel face of the RARα subtype: RARα is present in low amounts in the cytoplasm of mouse embryonic fibroblasts (MEFs) where it interacts with profilin2a (PFN2A), a small actin-binding protein involved in filaments polymerization. The interaction involves the N-terminal proline-rich motif (PRM) of RARα and the SH3-like domain of PFN2a. When increased in the cytoplasm, RARα competes with other PFN2a-binding proteins bearing PRMs and involved in actin filaments elongation. Consequently, the actin filament network is altered and MEFs adhesion is decreased. This novel role opens novel avenues for the understanding of pathologies characterized by increased levels of cytoplasmic RARα.


Assuntos
Citoesqueleto de Actina/metabolismo , Citoplasma/metabolismo , Fibroblastos/metabolismo , Profilinas/metabolismo , Receptor alfa de Ácido Retinoico/metabolismo , Animais , Células Cultivadas , Camundongos , Ligação Proteica , Mapeamento de Interação de Proteínas
2.
J Cell Sci ; 127(Pt 3): 521-33, 2014 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-24357724

RESUMO

Nuclear retinoic acid (RA) receptors (RARα, ß and γ) are ligand-dependent transcription factors that regulate the expression of a battery of genes involved in cell differentiation and proliferation. They are also phosphoproteins and we previously showed the importance of their phosphorylation in their transcriptional activity. In the study reported here, we conducted a genome-wide analysis of the genes that are regulated by RARs in mouse embryonic fibroblasts (MEFs) by comparing wild-type MEFs to MEFs lacking the three RARs. We found that in the absence of RA, RARs control the expression of several gene transcripts associated with cell adhesion. Consequently the knockout MEFs are unable to adhere and to spread on substrates and they display a disrupted network of actin filaments, compared with the WT cells. In contrast, in the presence of the ligand, RARs control the expression of other genes involved in signaling and in RA metabolism. Taking advantage of rescue cell lines expressing the RARα or RARγ subtypes (either wild-type or mutated at the N-terminal phosphorylation sites) in the null background, we found that the expression of RA-target genes can be controlled either by a specific single RAR or by a combination of RAR isotypes, depending on the gene. We also selected genes that require the phosphorylation of the receptors for their regulation by RA. Our results increase the repertoire of genes that are regulated by RARs and highlight the complexity and diversity of the transcriptional programs regulated by RARs, depending on the gene.


Assuntos
Adesão Celular/genética , Receptores do Ácido Retinoico/biossíntese , Animais , Diferenciação Celular/genética , Proliferação de Células , Fibroblastos/citologia , Fibroblastos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Fosforilação , Receptores do Ácido Retinoico/genética , Receptor alfa de Ácido Retinoico , Transdução de Sinais , Receptor gama de Ácido Retinoico
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