A novel isomerase protein as regulator of the activator protein-1 in trophoblast

DISERTANTE: ERLEJMAN A.G.

Bogotá, virtual Meeting

Congreso; IX SLIMP-Latin American Society for Materno Fetal Interaction and Placenta virtual Meeting ?Placenta ephemeral: but leaving an important and lasting imprint?; 2022

Latin American Society for Materno Fetal Interaction and Placenta

The study of signaling pathways involved in health disorders is relevant to the discovery of new targets for their treatment. It is known that some important pathways in uterus remodeling processes, such as the Activator Protein 1 (AP-1) and Nuclear Factor- B (NF- B), could be dysregulated in preeclampsia. AP-1 is mainly composed of two protein families (c-Fos and c-Jun). AP-1 dimers regulate proliferation, invasion and MMPs (matrix metalloproteinases) expression in trophoblast. FK506-Binding Proteins (FKBPs) are cochaperones with isomerase enzymatic activity (suppressed by FK506 drug). FKBPs regulate the activity of several transcription factors, including steroid receptors and NF- kB. Interestingly, preeclamptic placentas have shown alterations on c-Fos and FKBP52 expression. In this work we study the role of FKBPs on the biological function of trophoblast, particularly the relevance of FKBP52 enzymatic activity on AP-1 signaling. Different hallmarks in AP- 1 pathway were evaluated: extracellular signal regulated kinase (ERK) activation, c-Fos stability and nuclear retention, AP-1 transcriptional activity. Ours findings demonstrated that FKBP52 acts as a positive regulator of AP-1. Thus, the FKBP52 protein -mainly its isomerase activity is an interesting target to regulate AP-1 biological activity in trophoblast.