Post-translational modifications (PTM) by members of the Ubiquitin (Ub) family represent an efficient way to regulate protein function at several levels: to change their localisation, activity, their interaction with partner proteins or their stability at the right time and cellular compartment, according to the cell requirements. Defects in this homeostatic equilibrium result in pathologies such as cancer, neurodegeneration, inflammation or multiple infections. For this reason, this research area has become very attractive for fundamental scientists as well as for the pharmaceutical industry (Pharma) aiming to identify potential targets for therapeutic intervention. Interestingly, Ub and Ub-Like (UbL) proteins can modify themselves, forming intricate and complex chains. This landscape was recently expanded with the discovery of the formation of heterologous chains among UbL molecules including SUMO or NEDD8 but also other PTMs such as phosphorylation, acetylation or ribosylation. This unsuspected complexity of what is now called «The Ubiquitin Code», an unexplored universal language that needs to be deciphered to understand protein homeostasis and its associated pathologies. To decrypt this complex code requires joint collaborative multidisciplinary efforts at all levels, including the use of distinct molecular systems and model organisms and the latest technological developments to explore chemical, biochemical, molecular, pharmacological and clinical aspects of protein modification by members of the Ub family. UbiCODE represents an unprecedented effort to understand «the Ubiquitin Code» in an integrated manner.
Our key scientific challenge is to investigate how chain diversity is generated (written), regulated (edited), recognised (read) and connected with effector functions (interpreted) to regulate cellular plasticity. Our main hypothesis is that a better knowledge of the “writers”, “editors”, “readers” and “interpreters” of this new universal language will help us to understand the encoded message, which will be crucial to predict physiologic and pathologic processes.
