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Identification and characterization of new interactions among thyroid hormone receptors and proteins


Nuclear Receptors (RNs) are proteins that compose a superfamily of transcription factors generally modulated by ligands. The RNs are involved in several functions of the life organisms, regulating gene transcription related to many processes as differentiation, development, metabolism, and reproduction, among others. Additionally, the RNs are directly related to pathologies, being targets of many drugs, which acts in the treatment of type 2 diabetes and inflammation, or in hormonal regulation. In summary, RNs are important targets to the pharmaceutical industry, being particularly classified as targets in drug development studies for cancer and metabolic syndrome treatment.Given the importance to this class of proteins and their embracing actuation, it is very important to discover details of their mechanisms of action and their interactions with other molecules, even in cell environment or in vitro. In this context, this project aims the study of some nuclear receptors, as TR, through different approaches, which demand the identification of new complex formation among RNs and other proteins, in diverse cellular conditions, in the presence and absence of ligands. This mean goal of our project would be achieved through two hybrid and immunoprecipitation experiments. The identification of these new complexes and their regulation will provides us some subsidies to direct more specific studies that will include the structural, biophysical and cellular characterization. Furthermore, we intend to discover more information about gene regulation and ligand modulation in the context of these new complexes. The results will enlarge the knowledge about ways of action of these receptors, which contributes to the formulation of new interaction models that will help in planning new controlling strategies of this class of proteins, providing new insights to rational drug design. (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)
FATTORI, JULIANA; CAMPOS, JESSICA L. O.; DORATIOTO, TABATA R.; ASSIS, LUCAS M.; VITORINO, MARIELA T.; POLIKARPOV, IGOR; XAVIER-NETO, JOSE; FIGUEIRA, ANA CAROLINA M.. RXR Agonist Modulates TR: Corepressor Dissociation Upon 9-cis Retinoic Acid Treatment. MOLECULAR ENDOCRINOLOGY, v. 29, n. 2, p. 258-273, . (13/08743-2, 10/17048-8, 11/23725-5, 11/23659-2)
CAMPOS, JESSICA L. O.; DORATIOTO, TABATA R.; VIDEIRA, NATALIA B.; RIBEIRO FILHO, V, HELDER; BATISTA, FERNANDA A. H.; FATTORI, JULIANA; INDOLFO, NATHALIA DE C.; NAKAHIRA, MARCEL; BAJGELMAN, MARCIO C.; CVORO, ALEKSANDRA; et al. Protein Disulfide Isomerase Modulates the Activation of Thyroid Hormone Receptors. FRONTIERS IN ENDOCRINOLOGY, v. 9, . (16/22246-0, 13/07937-8, 11/23659-2, 13/08743-2, 14/22215-1)

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