Tricyclic antidepressants inhibit SUMO conjugation to FKBP51 and modulates its activity as a GR cochaperone

GOBBINI, ROMINA; SCHMIDT, MATHIAS; BINDER, ELISABETH; SOKN, CLARA*; SENIN, SERGIO; REIN, THEO; LIBERMAN, ANA CLARA; BUDZIÑSKI, MAIA LUDMILA*; UGO, BELÉN ; GASSEN, NILS; ARZT, EDUARDO

Mar del Plata

Congreso; LXIV Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2019

Sociedad Argentina de Investigación Clínica

FKBP51 is an Hsp90 co-chaperone that regulates the activity of the glucocorticoid receptor (GR) and is critical for the stress response. Abnormal FKBP51 function, and its impact on GR activity, has been widely associated to stress-related diseases and to the response to antidepressant (AD) treatment. Our group has demonstrated the key role of FKBP51 SUMO conjugation in the regulation of Hsp90-mediated inhibitory effect on GR activity. Taking this into consideration, we propose to study the role of antidepressants on FKBP51 SUMOylation and its impact on GR activity. We treated HEK293T cell with different antidepressants and performed Ni-NTA purification in order to enrich the cell extracts with SUMOylated proteins. We observed that ADs, and particularly Clomipramine (CLM), inhibit FKBP51 SUMOylation both in cells and in vitro assays (50.5±2.9%; p