Large scale profiling of the physiological impact of a potent anti-cancer agent inhibiting early protein maturation

Fumagillin and its derivatives are therapeutically-useful compounds for their capacity to reduce cancer progression. Fumagillin exerts a specific proliferation inhibition on endothelial cell lines and on several tumor lines. The specific molecular target of fumagillin is MetAP2, one of the two cytosolic MetAPs. MetAPs are in charge of N-terminal Methionine Excision, an essential pathway of cotranslational protein maturation. Why the inhibition of MetAP2 causes cell growth arrest in a subset class of cells is yet unknown. Here, we focus on a global large scale characterization of the N-terminal Methionine Excision pathway and the inhibition of one of its enzymes by fumagillin in a number of lines including cancer cell lines. N-termini profiling of responsive and unresponsive cells to fumagillin treatment was conducted using large scale proteomics approach