Modeling the oncogenic signaling circuitry in vivo: consequences of deregulated proline-directed phosphorylation in zebrafish embryogenesis

IBARRA SOLANGE; BORINI CARLA; GIRARDINI J.E.

Congreso; 2nd Meeting of the Latin American Zebrafish Network; 2012

LAZEN

Genetic and epigenetic alterations conspire to wire aberrant signaling circuits that allow changes in cell behaviour, propelling the acquisition of aggressive tumor phenotypes. Previous work allowed us to identify Pin1 as a critical link between oncogenic signaling and downstream mechanisms of aggressiveness. Pin1 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 modulation of biological responses. 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. In an attempt to characterize alterations elicited by Pin1 in vivo we are modeling Pin1 overexpression in zebrafish embryos, which provide a unique model to study pathways that govern development but are also altered in tumor cells. We have isolated a sequence coding for zebrafish Pin1 and analyzed gene expression during early development. Transient overexpression of Pin1 through microinjection of 1-cell embryos showed that forebrain is altered, suggesting that cell types involved in the development of this area are particularly sensible to Pin1 deregulation.