Understanding oncogenic signalling: Effect of Pin1 overexpression during embryogenesis in zebrafish

IBARRA SOLANGE; BORINI CARLA; GIRARDINI J.E.

Congreso; Molecular mechanisms in cell signaling and gene expresión. Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2013

Prolil-directed phosphorylation signaling regulates several physiologic processes. Pin1 is a key enzyme in this pathway that modulates the function of protein substrates through conformational changes induced by isomerization of peptide bonds in phosphorylated S-P or T-P motifs. The ability to link protein function with prolil-directed phosphorylation allows Pin1 to act as a global modulator of biological responses. However, incorrect regulation of Pin1 may promote pathological situations. Previously, we identified Pin1 as a critical link between oncogenic signaling and downstream mechanisms of tumor aggressiveness. However, the actual consequences of Pin1 overexpression in cancer are difficult to asses in vivo, due to the variety of substrates and the complex array of phosphorylation signals active in individual cell types. To characterize alterations elicited by Pin1 in vivo we are modeling Pin1 overexpression in zebrafish embryogenesis, which provides a unique model to study the effect on signaling pathways. We have previously shown that transient Pin1 overexpression affects forebrain development at early stages. We extended the analysis to later stages were we found that the effect of Pin1 on the telencephalon is maintained but also that structures surrounding the mandible are affected. Our results suggest, however, that the observed effects do not involve cartilage formation.