Molecular characterization of S6Ks in obesity and its associated diseases

• Grant number: 12/13558-7
• Support Opportunities: Research Grants - Young Investigators Grants
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Fernando Moreira Simabuco
• Grantee: Fernando Moreira Simabuco
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Associated researchers: Adriana Franco Paes Leme ; Marcio Alberto Torsoni ; Marcio Chaim Bajgelman ; Patrícia de Oliveira Prada
• Associated research grant(s): 18/14818-9 - Study of molecular targets important for the control of cancer metabolism: the mTOR/S6K pathway as a central role, AP.JP2
• Associated scholarship(s): 17/04269-5 - Proteomic analysis of A549 lung cancer cells treated with cisplatin and metformin, BP.IC; 16/02483-7 - Study of metformin effects in mTOR/S6Ks signal transduction pathway in lung cancer cells, BP.IC; 15/24475-3 - Modulation of expression of S6Ks in the central nervous system and its effects in obesity, BP.DD; + associated scholarships 15/16601-9 - Study of the relationship between NPM1 and NCL and different S6Ks isoforms, BP.IC; 15/00311-1 - Functional characterization of interacting proteins of different S6Ks isoforms, BP.MS; 14/07115-0 - Characterization of interacting partners of S6K1 short isoforms in human cells and its relationship with cancer, BP.IC; 13/22696-7 - Modulation of the S6Ks expression in the central nervous system and their effect in obesity, BP.MS; 12/23337-8 - Molecular characterization of S6Ks in obesity and its associated diseases., BP.JP - associated scholarships

Abstract

In the last years, the number of obese people has increased worldwidely, which also leads to an increase of a number of diseases associated with obesity such as diabetes type II, coronary artery disease, cerebrovascular accident, osteo-degenerative diseases and cancer. Therefore, there is currently a great demand for a better understanding of the biochemical and metabolic processes related to obesity, aiming the generation of knowledge and therapies that may improve the quality of life of human beings. The signal transduction pathway of the mTOR protein has recently been associated with the control of the energy balance of the body, working both as a sensor of the amount of nutrients available and as a signal to the usage or storage of that energy. This project aims to study in detail the molecular and cellular functions of a family of mTOR effector proteins, the protein kinases S6Ks, which have also been linked to obesity and its related illnesses. Among the open questions, we will focus on the biochemical study of the different isoforms of S6K, the cellular role of these proteins in regulating the expenditure / storage of energy and the function of these proteins in the body's metabolic control. A major effort will be the characterization of different interactomes of each S6Ks. Furthermore, the role of the different isoforms of S6Ks in cancer will be in particular evaluated, using prostate cancer as a model. Different cell types and tissues will be studied in order to have an overview of the molecular role of S6Ks in the body. (AU)

Scientific publications

(14)

(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)

SIMABUCO, FERNANDO MOREIRA; BETIM PAVAN, ISADORA CAROLINA; PESTANA, NATHALIE FORTES; CARVALHO, PAULO COSTA; BASEI, FERNANDA LUISA; GRANATO, DANIELA CAMPOS; PAES LEME, ADRIANA FRANCO; TONIN ZANCHIN, NILSON IVO. Interactome analysis of the human Cap-specific mRNA (nucleoside-2 `-O-)-methyltransferase 1 (hMTr1) protein. Journal of Cellular Biochemistry, v. 120, n. 4, p. 5597-5611, APR 2019. (12/13558-7)

CHAVES, FERNANDA MACHADO; BETIM PAVAN, ISADORA CAROLINA; SALVINO DA SILVA, LUIZ GUILHERME; DE FREITAS, LIDIA BROGLIO; ROSTAGNO, MAURICIO ARIEL; COSTA ANTUNES, ADRIANE ELISABETE; NEVES BEZERRA, ROSANGELA MARIA; SIMABUCO, FERNANDO MOREIRA. Pomegranate Juice and Peel Extracts are Able to Inhibit Proliferation, Migration and Colony Formation of Prostate Cancer Cell Lines and Modulate the Akt/mTOR/S6K Signaling Pathway. PLANT FOODS FOR HUMAN NUTRITION, v. 75, n. 1, p. 54-62, MAR 2020. (15/07299-7, 18/14818-9, 16/06457-0, 12/13558-7, 13/04304-4)

PINTO, ANA P.; DA ROCHA, ALISSON L.; KOHAMA, EIKE B.; GASPAR, RAFAEL C.; SIMABUCO, FERNANDO M.; FRANTZ, FABIANI G.; DE MOURA, LEANDRO P.; PAULI, JOSE R.; CINTRA, DENNYS E.; ROPELLE, EDUARDO R.; et al. Exhaustive acute exercise-induced ER stress is attenuated in IL-6-knockout mice. Journal of Endocrinology, v. 240, n. 2, p. 181-193, FEB 2019. (17/19869-8, 12/13558-7, 17/12765-2, 17/09038-1)

SALVINO DA SILVA, LUIZ GUILHERME; MORELLI, ANA PAULA; BETIM PAVAN, ISADORA CAROLINA; TAVARES, MARIANA ROSOLEN; PESTANA, NATHALIE FORTES; ROSTAGNO, MAURICIO ARIEL; SIMABUCO, FERNANDO MOREIRA; NEVES BEZERRA, ROSANGELA MARIA. Protective effects of beet (Beta vulgaris) leaves extract against oxidative stress in endothelial cells in vitro. Phytotherapy Research, v. 34, n. 6, JAN 2020. (16/06457-0, 12/13558-7, 13/04304-4, 18/14818-9)

DE VICENTE, LARISSA G.; PINTO, ANA P.; MUNOZ, VITOR R.; ROVINA, RAFAEL L.; DA ROCHA, ALISSON L.; GASPAR, RAFAEL C.; DA SILVA, LILIAN E. C. M.; SIMABUCO, FERNANDO M.; FRANTZ, FABIANI G.; PAULI, JOSE R.; et al. Tlr4 participates in the responses of markers of apoptosis, inflammation, and ER stress to different acute exercise intensities in mice hearts. Life Sciences, v. 240, JAN 1 2020. (12/13558-7, 17/09038-1, 18/14818-9, 18/12519-4, 17/19869-8, 17/12765-2)

MORELLI, ANA PAULA; TORTELLI, THARCISIO CITRANGULO JR JR; BETIM PAVAN, ISADORA CAROLINA; SILVA, FERNANDO RIBACK; GRANATO, DANIELA CAMPOS; PERUCA, GUILHERME FRANCISCO; PAULETTI, BIANCA ALVES; DOMINGUES, ROMENIA RAMOS; NEVES BEZERRA, ROSANGELA MARIA; DE MOURA, LEANDRO PEREIRA; et al. Metformin impairs cisplatin resistance effects in A549 lung cancer cells through mTOR signaling and other metabolic pathways. International Journal of Oncology, v. 58, n. 6, JUN 2021. (16/02483-7, 19/00607-9, 15/22814-5, 17/04269-5, 15/16601-9, 18/14818-9, 16/06457-0, 12/13558-7)

SIMABUCO, FERNANDO MOREIRA; BETIM PAVAN, ISADORA CAROLINA; PESTANA, NATHALIE FORTES; CARVALHO, PAULO COSTA; BASEI, FERNANDA LUISA; GRANATO, DANIELA CAMPOS; PAES LEME, ADRIANA FRANCO; TONIN ZANCHIN, NILSON IVO. Interactome analysis of the human Cap-specific mRNA (nucleoside-2 '-O-)-methyltransferase 1 (hMTr1) protein. Journal of Cellular Biochemistry, v. 120, n. 4, p. 15-pg., 2019-04-01. (12/13558-7)

PAVAN, ISADORA C. B.; YOKOO, SAMI; GRANATO, DANIELA C.; MENEGUELLO, LETICIA; CARNIELLI, CAROLINA M.; TAVARES, MARIANA R.; DO AMARAL, CAMILA L.; DE FREITAS, LIDIA B.; PAES LEME, ADRIANA F.; LUCHESSI, AUGUSTO D.; et al. Different interactomes for p70-S6K1 and p54-S6K2 revealed by proteomic analysis. PROTEOMICS, v. 16, n. 20, p. 2650-2666, OCT 2016. (14/01386-2, 13/22696-7, 12/13558-7)

MUNOZ, VITOR ROSETTO; GASPAR, RAFAEL CALAIS; KUGA, GABRIEL KEINE; BETIM PAVAN, ISADORA CAROLINA; SIMABUCO, FERNANDO MOREIRA; RAMOS DA SILVA, ADELINO SANCHEZ; DE MOURA, LEANDRO PEREIRA; CINTRA, DENNYS ESPER; ROPELLE, EDUARDO ROCHETE; PAULI, JOSE RODRIGO. The Effects of Aging on Rho-Kinase and Insulin Signaling in Skeletal Muscle and White Adipose Tissue of Rats. JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, v. 75, n. 3, p. 432-436, MAR 2020. (12/13558-7, 16/18488-8, 15/26000-2)

TAVARES, MARIANA ROSOLEN; LEMES, SIMONE FERREIRA; DE FANTE, THAIS; DE MIERA, CRISTINA SAENZ; BETIM PAVAN, ISADORA CAROLINA; NEVES BEZERRA, ROSANGELA MARIA; PRADA, PATRICIA OLIVEIRA; TORSONI, MARCIO ALBERTO; ELIAS, CAROL FUZETI; SIMABUCO, FERNANDO MOREIRA. Modulation of hypothalamic S6K1 and S6K2 alters feeding behavior and systemic glucose metabolism. Journal of Endocrinology, v. 244, n. 1, p. 71-82, JAN 2020. (12/13558-7, 13/22696-7, 18/14818-9, 18/07018-6, 15/24475-3, 16/06457-0)

AMARAL, CAMILA L.; FREITAS, LIDIA B.; TAMURA, RODRIGO E.; TAVARES, MARIANA R.; PAVAN, ISADORA C. B.; BAJGELMAN, MARCIO C.; SIMABUCO, FERNANDO M.. S6Ks isoforms contribute to viability, migration, docetaxel resistance and tumor formation of prostate cancer cells. BMC CANCER, v. 16, AUG 5 2016. (12/13558-7)

TAVARES, MARIANA R.; PAVAN, ISADORA C. B.; AMARAL, CAMILA L.; MENEGUELLO, LETICIA; LUCHESSI, AUGUSTO D.; SIMABUCO, FERNANDO M.. The S6K protein family in health and disease. Life Sciences, v. 131, p. 1-10, JUN 15 2015. (14/01386-2, 13/22696-7, 12/13558-7)

MENEGUELLO, LETICIA; BARBOSA, NATALIA M.; PEREIRA, KARINA D.; PROENCA, ANDRE R. G.; TAMBORLIN, LETICIA; SIMABUCO, FERNANDO M.; IWAI, LEO K.; ZANELLI, CLESLEI F.; VALENTINI, SANDRO R.; LUCHESSI, AUGUSTO D.. The polyproline-motif of S6K2: eIF5A translational dependence and importance for protein-protein interactions. Journal of Cellular Biochemistry, v. 120, n. 4, p. 6015-6025, APR 2019. (13/07467-1, 12/13558-7, 10/18095-0)

PAVAN, ISADORA C. B.; YOKOO, SAMI; GRANATO, DANIELA C.; MENEGUELLO, LETICIA; CARNIELLI, CAROLINA M.; TAVARES, MARIANA R.; DO AMARAL, CAMILA L.; DE FREITAS, LIDIA B.; PAES LEME, ADRIANA F.; LUCHESSI, AUGUSTO D.; et al. Different interactomes for p70-S6K1 and p54-S6K2 revealed by proteomic analysis. PROTEOMICS, v. 16, n. 20, p. 17-pg., 2016-10-01. (12/13558-7, 14/01386-2, 13/22696-7)