Fasciculation and elongation zeta-1 protein (FEZ1) interacts with the retinoic acid receptor and participates in transcriptional regulation of the Hoxb4 gene

Autor(es)

Teixeira, Mariana Bertini ^[1] ; Figueira, Ana Carolina M. ^[2] ; Furlan, Ariane S. ^[3] ; Aquino, Bruno ^[4] ; Alborghetti, Marcos R. ^[5] ; Leme, Adriana F. Paes ^[6] ; Wei, Li-Na ^[7] ; Kobarg, Jorg ^{[1, 8]}

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, Campinas, SP - Brazil

^[2] Ctr Res Energy & Mat, Brazilian Biosci Natl Lab, Spect & Calorimetry Lab, Campinas, SP - Brazil

^[3] Univ Cologne, Dept Biochem, Cologne - Germany

^[4] Univ Estadual Campinas, Struct Genom Consortium, Campinas, SP - Brazil

^[5] Univ Brasilia, Sch Hlth Sci, Dept Pharmaceut Sci, Brasilia, DF - Brazil

^[6] Ctr Res Energy & Mat, Brazilian Biosci Natl Lab, Mass Spectrometry Lab, Campinas, SP - Brazil

^[7] Univ Minnesota, Sch Med, Dept Pharmacol, Minneapolis, MN 55455 - USA

^[8] Univ Estadual Campinas, Fac Pharmaceut Sci, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FEBS OPEN BIO; v. 8, n. 1, p. 4-14, JAN 2018.
• Citações Web of Science: 1

Resumo

Fasciculation and elongation zeta-1 (FEZ1) protein is involved in axon outgrowth and is highly expressed in the brain. It has multiple interaction partners, with functions varying from the regulation of neuronal development and intracellular transport mechanisms to transcription regulation. One of its interactors is retinoic acid receptor (RAR), which is activated by retinoic acid and controls many target genes and physiological process. Based on previous evidence suggesting a possible nuclear role for FEZ1, we wanted to deepen our understanding of this function by addressing the FEZ1-RAR interaction. We performed in vitro binding experiments and assessed the interface of interaction between both proteins. We found that FEZ1-RAR interacted with a similar magnitude as RAR to its responsive element DR5 and that the interaction occurred in the coiled-coil region of FEZ1 and in the ligand-binding domain of RAR. Furthermore, cellular experiments were performed in order to confirm the interaction and screen for induced target genes from an 86-gene panel. The analysis of gene expression showed that only in the presence of retinoic acid did FEZ1 induce hoxb4 gene expression. This finding is consistent with data from the literature showing the hoxb4 gene functionally involved in development and acute myeloid leukemia, as is FEZ1. (AU)

• Processo FAPESP: 12/18796-3 - Caracterização da função fisiológica e patológica de membros da família de adaptadoras de transporte FEZ1/FEZ2
• Beneficiário: Jörg Kobarg
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 08/57906-3 - Instituto Nacional de Fotônica Aplicada à Biologia Celular - INFABIC
• Beneficiário: Hernandes Faustino de Carvalho
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 12/00792-1 - A função fisiológica e patológica de membros da família de adaptadoras de transporte FEZ1/FEZ2 no contexto da formação de núcleos multilobulados
• Beneficiário: Mariana Bertini Teixeira
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 15/11059-1 - O papel nuclear de FEZ1: interação com RAR e efeitos na transcrição gênica
• Beneficiário: Mariana Bertini Teixeira
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto