Protein Disulfide Isomerase Modulates the Activation of Thyroid Hormone Receptors

Autor(es):Mostrar menos -

Campos, Jessica L. O. ^{[1, 2]} ; Doratioto, Tabata R. ^{[1, 2]} ; Videira, Natalia B. ^{[1, 2]} ; Ribeiro Filho, V, Helder ; Batista, Fernanda A. H. ^[3] ; Fattori, Juliana ^[3] ; Indolfo, Nathalia de C. ^{[3, 4]} ; Nakahira, Marcel ^[5] ; Bajgelman, Marcio C. ^[3] ; Cvoro, Aleksandra ^[6] ; Laurindo, Francisco R. M. ^[7] ; Webb, Paul ^[8] ; Figueira, Ana Carolina M. ^[3]

Afiliação do(s) autor(es)

^[1] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, Sao Paulo - Brazil

^[2] State Univ Campinas Unicamp, Inst Biol, Grad Program Biosci & Bioact Prod Technol, Sao Paulo - Brazil

^[3] Ribeiro Filho, Helder, V, Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, Sao Paulo - Brazil

^[4] Ribeiro Filho, Helder, V, State Univ Campinas Unicamp, Inst Biol, Grad Program Biosci & Bioact Prod Technol, Sao Paulo - Brazil

^[5] State Univ Campinas Unicamp, Inst Chem IQ, Sao Paulo - Brazil

^[6] Methodist Hosp Res Inst, Genom Med, Houston, TX - USA

^[7] Univ Sao Paulo, Sch Med, Vasc Biol Lab, Heart Inst InCor, Sao Paulo - Brazil

^[8] Calif Inst Regenerat Med, Oakland, CA - USA

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN ENDOCRINOLOGY; v. 9, JAN 8 2019.
• Citações Web of Science: 0

Resumo

Thyroid hormone receptors (TRs) are responsible for mediating thyroid hormone (T3 and T4) actions at a cellular level. They belong to the nuclear receptor (NR) superfamily and execute their main functions inside the cell nuclei as hormone-regulated transcription factors. These receptors also exhibit so-called ``non-classic{''} actions, for which other cellular proteins, apart from coregulators inside nuclei, regulate their activity. Aiming to find alternative pathways of TR modulation, we searched for interacting proteins and found that PDIA1 interacts with TR beta) in a yeast two-hybrid screening assay. The functional implications of PDIA1-TR interactions are still unclear; however, our co-immunoprecipitation (co-IP) and fluorescence assay results showed that PDI was able to bind both TR isoforms in vitro. Moreover, T3 appears to have no important role in these interactions in cellular assays, where PDIA1 was able to regulate transcription of TR alpha and TR beta-mediated genes in different ways depending on the promoter region and on the TR isoform involved. Although PDIA1 appears to act as a coregulator, it binds to a TR surface that does not interfere with coactivator binding. However, the TR:PDIA1 complex affinity and activation are different depending on the TR isoform. Such differences may reflect the structural organization of the PDIA1:TR complex, as shown by models depicting an interaction interface with exposed cysteines from both proteins, suggesting that PDIA1 might modulate TR by its thiol reductase/isomerase activity. (AU)

• Processo FAPESP: 16/22246-0 - Mecanismos de repressão do PPAR gama como alvo para combate ao diabetes e obesidade
• Beneficiário: Ana Carolina Migliorini Figueira
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 11/23659-2 - Interação entre os receptores nucleares TR (receptores de hormônios tireoidianos), PPAR (receptores ativadores da proliferação dos peroxissomos) e outras proteínas celulares
• Beneficiário: Jéssica Christina Lóis de Oliveira Campos
• Linha de fomento: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 13/08743-2 - Indentificação e caracterização de novas interações entre os receptores de hormônios tireoidianos e proteínas
• Beneficiário: Ana Carolina Migliorini Figueira
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/22215-1 - Novas vias de sinalização moduladas pelo receptor de hormônio tireoidiano (TR) em câncer de mama
• Beneficiário: Jéssica Christina Lóis de Oliveira Campos
• Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto