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

CAMISAY M.F.; GALIGNIANA M.D.; DE LEO S.A.; ERLEJMAN A.G.; MAZAIRA G.I.

Tokio

Congreso; International Federation of Placenta Associations (IFPA 2018). Clinical Growth via Placenta?; 2018

International Federation of Placenta Associations

ObjectivesAP-1 dimers (composed by Jun and F03 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 characterized as co-chaperone with peptidylprolyl-isomerase enzymatic activity (suppressed by FK506 drug), it is known that regulates NF-kB and steroid receptors. Interestingly, preeclamptic placentas have shown alterations on c-fos and FKBP52 expression. The aim of this work was to characterize the effects of FKBP52, in particular the relevance of its enzymatic activity, on AP-1 signaling in trophoblastic cells.MethodsAs trophoblastic in vitro model BeWo cells were used. Cells were transfected tooverexpress FKBP52 (wild type or mutants) and stimulated with PMA. In order to block isomerase activity FKBP52 mutants (FKBP52F130Y and FKBP52F67Y) and FK506treatment were used. pERK/ERK, c-Fos and c-Jun expression/stability were evaluated by Western blot, c-fos localization by immunofluorescence, AP-1 transcriptional activity by luciferase assays, and MMP-2 proteolytic activity by zymographyResultsFKBP52 increased AP-1 transcriptional activity (100 fold with microg plasmid, P