Estudio del papel que desempaña la sumoilación de Rac1 en la diseminación del cáncer de mama

Abstract

RAC1 is a small GTPase belonging to the RHO family of GTPases that fulfils numerous important cellular functions, acting as a molecular switch in processes such as cell cycle, apoptosis and cell adhesion, among others. Furthermore, as a member of the RHO subfamily, it participates in the regulation of the actin cytoskeleton, which is necessary for cell movement and displacement.Due to its important functions, both the activity and subcellular localisation of RAC1 are very finely regulated. Like other small GTPases, RAC1 is active when bound to GTP and inactive when bound to GDP. Thus, RAC1 activity is controlled by activators (GEFs), which stimulate the exchange of GDP for GTP, and inhibitors (GAPs and RHOGDIs), which favour the inactive form of the protein. In addition, RAC1 activity is modulated by different post-translational modifications such as lipidation, which allows its anchoring to the membrane and regulates its binding to different effectors, or ubiquitination, which promotes its degradation in the proteasome. In addition, RAC1 can be modified by the ubiquitin-like peptide SUMO1. In contrast to ubiquitination, modification by SUMO1 contributes to modulate RAC1 activity by favouring the GTP-bound form of the protein. It is also noteworthy that this post-translational modification is unique in that it specifically regulates the ability of RAC1 to control cell migration...