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| Author(s): |
Annelize Zambon Barbosa Aragão
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia |
| Defense date: | 2014-01-07 |
| Examining board members: |
Adriana Franco Paes Leme;
Jörg Kobarg;
Carmen Veríssima Ferreira;
Solange Maria de Toledo Serrano;
Alexandre Keiji Tashima
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| Advisor: | Adriana Franco Paes Leme |
| Abstract | |
ADAM17 is a metalloprotease which plays an important role in regulatory mechanisms of cell signaling. It is responsible for shedding of the surface proteins, participating in regulation of important physiological processes, but it has also been associated with cancer progression and inflammatory processes. The aim of this study was to explore the regulation of ADAM17 by its cytoplasmic domain. In this regard, we used an approach based on co-immunoprecipitation followed by mass spectrometry (MS). Among the identified partners, the thioredoxin-1 (Trx-1) was selected, and its interaction has been validated using confocal microscopy, solid-phase binding assay, nuclear magnetic resonance and chemical cross-linking followed by MS. To understand the functional role of this interaction, experiments using cell-based assay were performed. Trx-1 overexpression decreases HB-EGF shedding upon ADAM17 activation. The discovery of a new interaction partner of ADAM17, which can modulate its activation, gives insights for novel studies to understand the mechanism of action of this metalloprotease (AU) | |
| FAPESP's process: | 09/18301-1 - Study of the regulation of recombinant ADAM-17 by determining phosphorylation sites of the cytoplasmic domain and its ligands in normal and cancer cells. |
| Grantee: | Annelize Zambon Barbosa Aragão |
| Support Opportunities: | Scholarships in Brazil - Doctorate |