A função fisiológica e patológica de membros da família de adaptadoras de transporte FEZ1/FEZ2 no contexto da formação de núcleos multilobulados

• Grant number: 12/00792-1
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: August 01, 2012
• End date: August 04, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Jörg Kobarg
• Grantee: Mariana Bertini Teixeira
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
• Associated scholarship(s): 15/11059-1 - Nuclear role of FEZ1: interaction with RAR and effects on gene transcription, BE.EP.DD

Abstract

The protein UNC-76 was identified as an essential component for axon fasciculation and elongation in the worm C. celegans. In the same line its mammalian otholog FEZ1 presents neuronal expression and its gene knock out in mice showed behaviour changes and slight neurological disorders. Our goups work showed that FEZ1 is a multifuncional (hub) protein, that interacts with many other proteins, is a natively unfolded protein, and a dimer in solution. This all suggests that FEZ1 acts at the cytoskleton as a dimeric and bivalent transport adaptor. This hypothesis is further supported by the observation that FEZ1 interacts and colocalizes with cytoskeleton elements (e.g., tubulina, CLASP2) and motor proteins of the kinesin family (FIF3A). In this context the super-expression of FEZ1, in HEK293 cells, provokes the generation of "flower-like" nuclei in more than 40% of transfected cells. This dramatic cellular phenotype is commonly found in certain leukemias and has been associated to an increased drug resistance of the cells. The human paralogue FEZ2 shows ubiquitous expression and interacts with all FEZ1 interacting proteins and additional 19 proteinas. This suggest that FEZ2 may have gained new functions. Here, we want to study the functional role of FEZ1, FEZ2 and Scoco (FEZ1 interactor) and mechanistic aspects related to the formation of the "flower-like" nuclei after FEZ1 super-expression in certain cancer types. Therefore we want to generate FEZ2 knock out mice and characterize them funcionally. Furthermore, we want to adress the role of Fez1 and Scoco in the nucleus in the contexto of transcriptional regulation. We also want to identify other proteins involved in the formation of the "flower-like" nuclei induced by FEZ1 super-expressão, by mass spectrometry proteome/interactome anlayses. Finally, we will perform iRNA knock down experiments and microarray studies. (AU)

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, JAN 2018. (12/18796-3, 12/00792-1, 15/11059-1)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

TEIXEIRA, Mariana Bertini. Physiology and pathology of protein FEZ1: characterization of the interaction with retinoic acid receptor and evaluation of its expression in acute myeloid leukemia. 2017. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.