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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

ADAM17 cytoplasmic domain modulates Thioredoxin-1 conformation and activity

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Author(s):
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e Costa, Rute A. P. [1] ; Granato, Daniela C. [1] ; Trino, Luciana D. [1] ; Yokoo, Sami [1] ; Carnielli, Carolina M. [1] ; Kawahara, Rebeca [2, 1] ; Domingues, Romenia R. [1] ; Pauletti, Bianca Alves [1] ; Neves, Leandro Xavier [1] ; Santana, Aline G. [1] ; Paulo, Joao A. [3] ; Aragao, Annelize Z. B. [1] ; Heleno Batista, Fernanda Aparecida [1] ; Migliorini Figueira, Ana Carolina [1] ; Laurindo, Francisco R. M. [4] ; Fernandes, Denise [4] ; Hansen, Hinrich P. [5] ; Squina, Fabio [6] ; Gygi, Steven P. [3] ; Paes Leme, Adriana F. [1]
Total Authors: 20
Affiliation:
[1] CNPEM, Lab Nacl Biociencias, LNBio, Campinas, SP - Brazil
[2] Macquarie Univ, Dept Mol Sci, Sydney, NSW - Australia
[3] Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 - USA
[4] Univ Sao Paulo, Fac Med, Inst Coracao, Sao Paulo, SP - Brazil
[5] Univ Hosp Cologne, CECAD Res Ctr, Dept Internal Med 1, Cologne - Germany
[6] Univ Sorocaba, Dept Proc Tecnol & Ambientais, Sao Paulo - Brazil
Total Affiliations: 6
Document type: Journal article
Source: REDOX BIOLOGY; v. 37, OCT 2020.
Web of Science Citations: 0
Abstract

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 (ADAM17cyto(F730A)) 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 Cys(824) at the C-terminal of ADAM17cyto with the Cys(73) 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. (AU)

FAPESP's process: 16/01528-7 - The effect of Trx-1 overexpression on protein expression and redox state of cysteines by iodoTMT and TMT labeling
Grantee:Rute Alves Pereira e Costa
Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
FAPESP's process: 18/12194-8 - Immobilization of multiple potential biomarkers, pure and obtained from liquid biopsies, in Metal-Organic Frameworks (MOFs) as biosensors applied in head and neck Cancer diagnosis and prognosis
Grantee:Luciana Daniele Trino Albano
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 19/18751-9 - Discovery and validation of prognostic candidates for oral cancer in liquid biopsies.
Grantee:Daniela Campos Granato
Support Opportunities: Scholarships in Brazil - Young Researchers
FAPESP's process: 18/18496-6 - The role of alcohol treated-extracellular vesicles in oral cells transformation
Grantee:Adriana Franco Paes Leme
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 09/54067-3 - Acquisition of a mass spectrometer coupled to a liquid chromatography system for increasing the capacity to meet the needs of users and for making new technologies available in the Laboratory of Mass Spectrometry
Grantee:Adriana Franco Paes Leme
Support Opportunities: Multi-user Equipment Program
FAPESP's process: 18/15535-0 - From discovery to validation of prognostic candidates for oral cancer in liquid biopsies
Grantee:Daniela Campos Granato
Support Opportunities: Research Grants - Young Investigators Grants
FAPESP's process: 14/23888-0 - Studies on the activation mechanisms of MMP-2 and ADAM17: identification of regulatory proteins, oxidant production pathways, epigenetics and proteolytic targets
Grantee:Raquel Fernanda Gerlach
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 16/07846-0 - Peptidomic analysis of extracelular vesicles originated from cell lines, saliva and plasma from oral squamous cell carcinoma
Grantee:Adriana Franco Paes Leme
Support Opportunities: Regular Research Grants
FAPESP's process: 16/24664-3 - Finding binding parterns of Agrin fragments to study their role on the Oral Cancer progression
Grantee:Aline Guimarães Santana
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 14/06485-9 - Investigation of the ADAM17 metalloproteinase regulation mechanism by the interaction with Trx-1
Grantee:Rute Alves Pereira e Costa
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 10/19278-0 - Study of regulation of ADAMs in oral cancer
Grantee:Adriana Franco Paes Leme
Support Opportunities: Research Grants - Young Investigators Grants