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ADAM17 cytoplasmic domain modulates Thioredoxin-1 conformation and activity.
E Costa, Rute A P; Granato, Daniela C; Trino, Luciana D; Yokoo, Sami; Carnielli, Carolina M; Kawahara, Rebeca; Domingues, Romênia R; Pauletti, Bianca Alves; Neves, Leandro Xavier; Santana, Aline G; Paulo, Joao A; Aragão, Annelize Z B; Heleno Batista, Fernanda Aparecida; Migliorini Figueira, Ana Carolina; Laurindo, Francisco R M; Fernandes, Denise; Hansen, Hinrich P; Squina, Fabio; Gygi, Steven P; Paes Leme, Adriana F.
Afiliación
  • E Costa RAP; Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, São Paulo, Brazil.
  • Granato DC; Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, São Paulo, Brazil.
  • Trino LD; Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, São Paulo, Brazil.
  • Yokoo S; Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, São Paulo, Brazil.
  • Carnielli CM; Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, São Paulo, Brazil.
  • Kawahara R; Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, São Paulo, Brazil.
  • Domingues RR; Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, São Paulo, Brazil.
  • Pauletti BA; Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, São Paulo, Brazil.
  • Neves LX; Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, São Paulo, Brazil.
  • Santana AG; Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, São Paulo, Brazil.
  • Paulo JA; Department of Cell Biology, Harvard Medical School, Boston, USA.
  • Aragão AZB; Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, São Paulo, Brazil.
  • Heleno Batista FA; Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, São Paulo, Brazil.
  • Migliorini Figueira AC; Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, São Paulo, Brazil.
  • Laurindo FRM; Instituto Do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
  • Fernandes D; Instituto Do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
  • Hansen HP; Department of Internal Medicine I, University Hospital Cologne, CECAD Research Center, Cologne, Germany.
  • Squina F; Universidade de Sorocaba, Departamento de Processos Tecnológicos e Ambientais, São Paulo, Brazil.
  • Gygi SP; Department of Cell Biology, Harvard Medical School, Boston, USA.
  • Paes Leme AF; Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, São Paulo, Brazil. Electronic address: adriana.paesleme@lnbio.cnpem.br.
Redox Biol ; 37: 101735, 2020 10.
Article en En | MEDLINE | ID: mdl-33011677
The activity of Thioredoxin-1 (Trx-1) is adjusted by the balance of its monomeric, active and its dimeric, inactive state. The regulation of this balance is not completely understood. We have previously shown that the cytoplasmic domain of the transmembrane protein A Disintegrin And Metalloprotease 17 (ADAM17cyto) binds to Thioredoxin-1 (Trx-1) and the destabilization of this interaction favors the dimeric state of Trx-1. Here, we investigate whether ADAM17 plays a role in the conformation and activation of Trx-1. We found that disrupting the interacting interface with Trx-1 by a site-directed mutagenesis in ADAM17 (ADAM17cytoF730A) caused a decrease of Trx-1 reductive capacity and activity. Moreover, we observed that ADAM17 overexpressing cells favor the monomeric state of Trx-1 while knockdown cells do not. As a result, there is a decrease of cell oxidant levels and ADAM17 sheddase activity and an increase in the reduced cysteine-containing peptides in intracellular proteins in ADAM17cyto overexpressing cells. A mechanistic explanation that ADAM17cyto favors the monomeric, active state of Trx-1 is the formation of a disulfide bond between Cys824 at the C-terminal of ADAM17cyto with the Cys73 of Trx-1, which is involved in the dimerization site of Trx-1. In summary, we propose that ADAM17 is able to modulate Trx-1 conformation affecting its activity and intracellular redox state, bringing up a novel possibility for positive regulation of thiol isomerase activity in the cell by mammalian metalloproteinases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tiorredoxinas / Cisteína / Proteína ADAM17 Límite: Humans Idioma: En Revista: Redox Biol Año: 2020 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tiorredoxinas / Cisteína / Proteína ADAM17 Límite: Humans Idioma: En Revista: Redox Biol Año: 2020 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Países Bajos