AP-1 IS MODULATED BY FK506-BINDING PROTEIN 52

CAMISAY MF, DE LEO S, FONTANA V, CONVERSO D, GALIGNIANA MD, ERLEJMAN A

Conferencia; LXI Reunión Anual de SAIC; 2016

The FK506 -binding protein 52(FKBP52) has been described as an important regulator of steroid receptors and some transcription factors, such as NF-kappaB and p53.In this study, we demostrated that FKBP52 enhances ERK1/2-signalling and AP-1 (activator protein 1) transcription activity, thus increasing expression or activity of target genes. FKBP52 has two key sequences: tetratricopeptide repeat (TPR) domain and the peptidylprolyl-isomerase (PPIase) domain, where its catalytic site is located. Transcriptional activity of AP-1 was evaluated by luciferase assays. HEK293T were transfected with expression vectors, pCI-neo-FKBP52wt and its puntual mutants of each domain(FKBP52K354A, FKBP52F67Y and FKBPP52F130Y). FKBP52 stimulated AP-1 transcription activity on a concentration dependent manner, which was significantly abolished by the expression of both mutants. As AP-1 protein is critical at invasion of human trophoblast we were interested in studying the AP-1 modulation by FKBP52 in a vitro choriocarcinoma model (BeWo). ERK1/2-signalling was evaluated at protein level. FKBP52 stabilized the phosphorilation of ERK1/2 along time. Besides, in order to analize the effects of these regulatory events, we studied IL-6 secretion (ELISA) and MMP-2 proteolytic activity (zymography). We observed an increased IL-6 medium concentration and MMP-2 enzimatic activity, abrogated by the mutants of FKBP52.Based on our experiments, we concluded that FKBP52 is an positive regulator of AP-1 and its effects are dependent on its both domains.