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Nuclear role of FEZ1: interaction with RAR and effects on gene transcription

Grant number: 15/11059-1
Support type:Scholarships abroad - Research Internship - Doctorate (Direct)
Effective date (Start): September 15, 2015
Effective date (End): September 14, 2016
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal researcher:Jörg Kobarg
Grantee:Mariana Bertini Teixeira
Supervisor abroad: Li-Na Wei
Home Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovações (Brasil). Campinas , SP, Brazil
Research place: University of Minnesota (U of M), United States  
Associated to the scholarship: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, BP.DD

Abstract

The protein UNC-76 was identified as an essential component for axon fasciculation and elongation in the worm C. elegans. The human proteins FEZ (fasciculation and elongation protein zeta) are the mammalian orthologs of UNC-76 and are necessary for normal axonal outgrowth and fascicle structure. Regarding its structure, FEZ1 has a C-terminal region involved in protein-protein interactions and a N-terminal region that serves as a platform for dimerization. Also FEZ1 is natively unfolded, convenient to its role as a hub protein. Functionally, it was shown that the interactor partners of FEZ1 are involved in neural cell development, microtubule and transport, apoptosis, and transcriptional control. We hypothesized that through its interaction with retinoic acid receptor (RAR), FEZ1 may have a role in the nucleus. Retinoic acid (RA) is known as a pleiotropic agent that regulates many gene targets through its binding to nuclear receptors (RAR/RXR). The "on/off" switch of these receptors involves recruitment of coactivators, corepressors and coregulators and also chromatin remodeling. The aim of this project is to characterize the interaction between FEZ1 protein and RA receptor and provide a mechanism for the function of FEZ1 in gene regulation. Our recent data shed light on the interface of this interaction, the participation of ligand RA in vivo and in vitro and the role of FEZ1 in this system. We want to go further on this investigation through experiments involving mammalian cells and reporter systems, chromatin immunoprecipitation, enzymatic assay, RT-PCR and in vitro transcription. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
TEIXEIRA, MARIANA BERTINI; FIGUEIRA, ANA CAROLINA M.; FURLAN, ARIANE S.; AQUINO, BRUNO; ALBORGHETTI, MARCOS R.; LEME, ADRIANA F. PAES; WEI, LI-NA; KOBARG, JORG. Fasciculation and elongation zeta-1 protein (FEZ1) interacts with the retinoic acid receptor and participates in transcriptional regulation of the Hoxb4 gene. FEBS OPEN BIO, v. 8, n. 1, p. 4-14, . (12/18796-3, 12/00792-1, 15/11059-1)

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