Linking small GTPase signaling with mRNA regulation: functional study of b2-chimaerin and G3BP interaction.

FEDERICO COLUCCIO LESKOW; OMAR A COSO; ELIZABETH JARES-ERIJMAN

Bariloche, Argentina

Congreso; ICGEB and EURASNET meetings on "Gene Expression and RNA processing" and "Cell Biology, Signaling and Alternative Splicing"; 2007

ICGEB, EURASNET, AGENCIA

The small GTPases are important nodes in signal transduction pathways. These proteins switch between an active (GTP-bound) state and an inactive (GDP-bound) state. This balance is regulated by the activation of GTP Exchange Factors (GEFs) and GTPase Activating Proteins (GAPs) and controls different processes including; cell movement, cell cycle regulation, proliferation, differentiation and the remodeling of the acting cytoskeleton. The post-transcriptional regulation of mRNAs is a crucial event directing these processes. β2-chimaerin is a multi-domain protein with Rac-GAP activity. Using a proteomic approach we identified G3BP (Ras-GAP SH3-domain binding protein-1) as a β2- chimaerin interacting protein.    G3BP is an RNA binding protein with endonuclease activity known to bind and regulate the stability and localization of mRNAs. It was shown to be involved both in the degradation of mRNAs, such as the one coding for c-Myc, and in the stabilization and localization of others such as Tau. The Drosophila homolog Rasputin (Rin) was first identify as a gene involved in linking Ras and Rho signaling. Several lines of evidences suggest that G3BP is involved in both mRNA regulation and small GTPase signaling.      In the present work, we evaluate the role of he interaction between β2- chimaerin and G3BP in linking small GTPase signaling to the regulation of stability, localization and degradation of mRNAs.