Methionine aminopeptidase 2 (MetAP2), a
proteolytic enzyme that removes the N-terminal
methionine from newly synthesized cellular
proteins, plays roles in the development of various
cancers and has been found to be over-expressed in
cholangiocarcinoma (CCA).
Fumagillin, a specific MetAP2 inhibitor, suppresses CCA cell proliferation. In order to determine the molecular mechanisms involved in the suppression of CCA cell proliferation caused by
fumagillin, proteomic analysis was performed on
fumagillin-treated CCA cells.
Proteins affected by
fumagillin were analyzed using 2D gel electrophoresis and matrix-assisted
laser desorption ionization- time of flight tandem mass spectrometry (MALDI-TOF/TOF). The results showed that the processed form of
cyclophilin A (CypA) was greatly decreased in parallel with the suppression of CCA cell proliferation. These results suggest that CypA is possibly a
protein substrate of MetAP2 cleavage. Removal of N-terminal
methionine by MetAP2 may be essential for proper function of CypA in CCA cell proliferation. MetAP2 and CypA may thus serve as potential therapeutic targets for CCA treatment.