Dataset Information

ADAM17 cytoplasmic domain modulates Thioredoxin-1 conformation and activity

ABSTRACT: We have demonstrated that site-directed mutagenesis in ADAM17 (ADAM17cytoF730A) also disrupts the interacting interface with Trx-1, resulting in a decrease of Trx-1 reductive capacity and activity. One of the mechanisms that explain this effect might be that ADAM17cyto favors Trx-1 monomerization state - the active state - by forming a disulfide bond between Cys824 at the C-terminal of ADAM17cyto with the Cys73 of Trx-1, which is involved in the dimerization site. Moreover, we observed that ADAM17 overexpressing or knockdown cells favors or not the monomeric state of Trx-1, respectively. As a result, there is a decrease of oxidant levels and ADAM17 sheddase activity, and an increase in the reduced cysteine-containing peptides in intracellular proteins in ADAM17cyto overexpressing cells. In summary, we propose that ADAM17 is able to modulate Trx-1 conformation affecting its activity and intracellular redox state.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

SUBMITTER: Adriana Franco Paes Leme