Protein maturation,
cell fate and therapeutics

It is recognized that the majority of proteins, to become functional actives, needs to undergo several modifications, which are most of the time catalyzed by specific enzymes. Recently the term of epiproteome has been coined and referred to the set of protein modifications (PTMs) made to proteins in a cellular compartment, cell or organism and in a given context. Although more than 660 different PTMs have been identified up to now, the extent of the epiproteome is still largely unknown. However, it is now clear that PTMs reflect a specific physiologic, metabolic or differentiation state of the cells or its adaptation to endogenous or exogenous stress conditions, such as the reciprocal response of the host and pathogens during infection. Thus, PTMs are necessarily of critical importance in translational research and drug development.

The global objective of our research is to get the picture and to provide relevant tools to better evaluate the yet underestimated but essential area of epiproteomics by focusing on N-terminal protein modifications (NPMs), as original example studied in various contexts. NPMs correspond to a variety of chemical modifications occurring on most proteins which imprinting starts in the course of their synthesis as soon as the polypeptide chains emerge while being still bound to the ribosome. NPMs involve proteolytic events including N-terminal Methionine Excision (NME) and additions such as acylations, which correspond to N-α-acetylation (NTA) or N-Myristoylation (MYR) (Fig. 1).