Hsp90 co-chaperone FKBP51, is up-regulated upon serum deprivation and may play an important role in regulating metabolic stress

GOBBINI, R.; SOKN, C.; BUDZIÑSKY, M.L.; SENIN, S.; ERDOCIA, M.; ARZT, E.; LIBERMAN, A.C.

Mar del Plata

Congreso; LXIII Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2018

Sociedad Argentina de Investigación Clínica (SAIC)

The hypothalamic-pituitary-adrenal (HPA) axis plays a fundamental role in the response to external and internal stimuli. FK506-binding protein 51 (FKBP51) is an Hsp90 co-chaperone that tightly regulates the glucocorticoid receptor (GR) activity and therefore is critical for the stress response. FKBP51 inhibits GR activity and in order to act as a GR regulator FKBP51 has to be SUMOylated. Interestingly FKBP51 has also been described as an important regulator of energy balance playing an important role in metabolic homeostasis. Both stress and metabolic regulation share common regulatory pathways centered in the hypothalamus. FKBP51 shows high expression in the hypothalamus and may act as an interplayer between both pathways. Exposure to nutrient overload or to nutrient inhibition is considered to be a metabolic stressor. In this work we show that FKBP51 expression is up-regulated upon serum deprivation in HEK 293 cultured cells. Also, we demonstrate by co-inmunoprecipitation assays that FKBP51 interaction with AKT1 and Beclin1, which are tightly involved in the metabolic status of the cell, is differentially affected when FKBP51 is SUMOylated, and hat this interaction seems to be altered when the cells are exposed to a lack of nutrients.