Activating protein 1 (AP-1) signaling pathway in trophoblastic cells: characterization of a novel isomerase protein on its regulation

CAMISAY, MF; FONTANA, V; MAZAIRA, G; ERLEJMAN, A; DE LEO, S; GALIGNIANA, M.D.

Tokyo

Congreso; International Federation of Placenta Association (IFPA); 2018

International Federation of Placenta Association (IFPA)

AP-1 dimers (composed by Jun and Fos family proteins) regulate proliferation, invasion and MMP (matrix metalloproteinase) expression in trophoblast. c-Fos and c-Jun are unstable proteins, whose activation involves the coordinated regulation of stability, nuclear translocation, and transactivation activity. FK506-binding protein 52 kDa (FKBP52), first characterizes as co-chaperone with peptidylprolyl-isomerase enzymatic activity (suppressed by FK506 DRUG), it is known that regulates NF-kB and steroid receptors. Interestingly, pleeclamptic placentas have shown alterations on c-fos and FKBP52 expression. The aim of this work was to charactrize the effects of FKBP52, in particular the relevace of its enzymatic activity, on AP-1 signaling in trophoblastic cells.As trophoblastic in vitro model BeWo cells were used. Cells were transfected to overexpress FKBP52 (wild type or mutants) and stimuklated with PMA. In order to block isomerase activity FKBP52 mutants (FKBP52F130Y and FKBP52F67Y) and FK506 treatment were used. pERK/ERK, c-Fos and c-Jun expression/stability were evaluated by Western blot, c-fos localization by immunofluorscence, AP.1 transcriptional activity by luciferase assays, and MMP-2 proteolytic activity by zymography.FKBP52 inceased AP-1 transcriptional activity (100 fold with 1ug plasmid, p