Identification of the mechanisms of phosphorylation of PPARy and its relations with the recruitment of corepressors

• Grant number: 16/13480-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2016
• End date: December 31, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Ana Carolina Migliorini Figueira
• Grantee: Thaís Helena Tittanegro
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
• Associated scholarship(s): 17/12314-0 - Inhibition of LXR alpha phosphorylation: evaluating target gene expression effects and LXR alpha and PPAR gamma crosstalk, BE.EP.MS

Abstract

The active peroxisome proliferator-activator receptor ³ (PPAR³) is a potentialtarget for the class of thiazolidinediones (TZD) also known as glitazone, drugs responsible forthis sensitization to insulin in patients with diabetes mellitus type 2. However, its use hasbeen administered with great caution due to its major side effects including weight gain,fluid retention, bone loss, hemodilution, and heart failure appears in more than 15% ofpatients. Recently, studies have demonstrated that the action of the drug occurs mainly byinhibiting cyclin-dependent kinase (Cdk5) conducting the phosphorylation of Ser273 residuePPAR³, improve insulin sensitivity. However, this drug also causes activation of NR resultingin undesirable side effects such as increased adipose tissue by adipogenesis specificallyregulated by PPAR³. In the search for the ideal ligand to NR, opens a wide field of research,where it seeks a molecule able to bind to the PPAR³ without causing its activation, but alsobe able to protect the site of the Ser273 residue against phosphorylation by Cdk5.Therefore, it is necessary to elucidate which the actual correlation between thephosphorylation of the Ser273 residue mechanisms and corepressor recruitmentmechanisms, these recruited as the PPAR³ is not linked to any ligand.

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)

DIAS, MARIELI MARIANO GONCALVES; BATISTA, FERNANDA APARECIDA HELENO; TITTANEGRO, THAIS HELENA; DE OLIVEIRA, ANDRE GUSTAVO; LE MAIRE, ALBANE; TORRES, FELIPE RAFAEL; FILHO, HELDER VERAS RIBEIRO; SILVEIRA, LEONARDO REIS; FIGUEIRA, ANA CAROLINA MIGLIORINI. PPAR gamma S273 Phosphorylation Modifies the Dynamics of Coregulator Proteins Recruitment. FRONTIERS IN ENDOCRINOLOGY, v. 11, NOV 27 2020. (19/14465-1, 16/13480-9, 16/22246-0)

Academic Publications

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

TITTANEGRO, Thaís Helena. Identification of PPAR gamma phosphorylation mechanisms and the relationship with corepressors recruitment. 2018. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.