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

BUDZINSKI, MAIA LUDMILA; ARZT, EDUARDO; GOBBINI, ROMINA PAULA; SENIN, SERGIO; LIBERMAN, ANA CLARA; SOKN, MARÍA CLARA; ERDOCIA, MARIANA

Mar del Plata

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2018

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 plays a fundamental role in regulating the glucocorticoid receptor (GR) activity and therefore keeping the HPA axis functioning. FKBP51 inhibits GR activity by decreasing GR hormone-binding affinity and nuclear translocation. In order to act as a GR regulator, FKBP51 needs to be SUMOylated, a process enhanced by the SUMO E3 ligase, PIAS4. 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 a 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 upregulated upon serum deprivation in HEK 293 cultured cells. Also, we demonstrate by co-immunoprecipitation 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 that this interaction seems to be altered when cells are exposed to a lack of nutrients.