Pérez-Sala Gozalo, Dolores
91 837 3112 Extension: 4212/4211
Protein posttranslational modification is an essential mechanism for the regulation of protein structure and activity in response to endogenous mediators, toxins and therapeutic agents. Protein posttranslational processing increases the possibilities of regulation, since the same protein can give rise to multiple species differing in their subcellular localization, interactions or functions, the nature of which depends on the structure of the modification. Proteins constitute platforms for the integration of signalling from biological agents, reactive species and drugs, which may alter different residues in the same protein and compete or cooperate for the modification of certain residues.
Our work aims at the structural and functional characterization of novel types of posttranslational modifications, the identification of their protein targets and their pathophysiological consequences in the context of inflammation and carcinogenesis and in the mechanisms of drug action. In addition, we are interested in the identification of key residues which can suffer structurally diverse modifications and in elucidating the role they play in the integration of signalling pathways. Cysteine residues are among the amino acids which can undergo a wider number of structurally different modifications.
We have identified and characterized various modifications of cysteine residues in members of the Ras and Rho protein families, which differentially regulate their stability or signalling platforms. In addition, we have studied the modification of catalytic cysteines in enzymes involved in chemoresistance, including proteins of the aldo-keto reductase and glutation transferase families, which could open new perspectives for the development of antitumoral strategies. More recently, we are pursuing the elucidation of novel roles of the modification of cytoskeletal proteins and of proteins involved in vesicular traffic.