STUDY OF ISOMERASE PROTEINS AS NEW REGULATORS IN THE ACTIVATION OF TRANSCRIPTION FACTORS RELATED TO STRESS AND INFLAMMATION

ERLEJMAN A.G.

Buenos Aires

Congreso; LXII Reunión anual de la Sociedad Argentina de Investigación Clínica (SAIC) en el marco de la Reunión Conjunta de Sociedades de Biociencias; 2017

Sociedad Argenitna de Investigación Clínica

Trabajoseleccionado para presentación oral para competir por el premio Joveninvestigador SAIC 2017. Oradora Erlejman AGThe study of  proteins involved inbiological response are important in order topromote the discover of new regulators in signalling pathways.  In certain malignancies,it is know that some signalling are altered, such as Nuclear Factor Kappa B (NF-kB)and Activator Protein 1 (AP-1) in chronic inflammation.  In particular we study new regulators of activation of transcription factors related to stress and inflammation as NF-kB and AP-1, with the final goal of provide new molecular target asa promising approach in therapeutic field .FK506-bindingproteins (FKBPs) are Hsp90 Co-chaperons withpeptidylprolyl-isomerase enzimaticactivity, suppressed by the FK506 drug. PreviouslyFKBP51 and FKBP52 werecharacterized as modulators steroid receptors. We demonstrated that FKBP51 impairs NF-kB(p65/p50) activity, while FKBP52 enhance it.Furthermore, NF-kB target genes were large expressed by FKBP52, and its isomerase activity was decisive in this regulation. Importantly, both basal phopho-p65 and total p65 protein level were increased by FKBP52. In this context NF-kB activity was favored by a higher FKBP52/FKBP51 ratio. Moreover, in trophoblast cells AP-1 has an important regulating role and has been detected alteration c-fos, as well as low FKBP52 expression in placentas frompreeclampsia. Ours finding revealed that FKBP52 stimulated AP-1 transcriptional activity and promoted greater c-fos protein level.Interestingly, the over expressed FKBP52 produced higher level of pERK/ERK for longer time. Wepropose FKBP52 as new key regulator on AP-1and NF-kB signalling, remarking its isomerase activity as essential. Thus,we suggest FKBP52isomeraseactivity as an interesting targetin orderto prevent AP-1 and NF-kBbiologicalactivity.This finding represent a novel contribution inthe developmentof new therapeutic agents for inflammatory diseases. Financialsupport: UBA, CONICET and PICT 2015-1603.Keywords: AP-1, c-fos, NF-kB, FKBP52