NERVE GROWTH-FACTOR INDUCED NEURITE OUTGROWTH FROM AMPHIBIAN NEUROEPITHELIAL PRECURSOR CELLS IS PREVENTED BY DIPEPTIDES INHIBITING UBIQUITIN-MEDIATED PROTEOLYSIS

The effect of dipeptides known to inhibit the ubiquitin-mediated prote olysis has been examined on growth factor induced neurite outgrowth fr om amphibian neuroepithelial precursor cells in primary culture. Nerve growth factor (NGF) stimulated neuritogenesis from these cells but fi broblast growth factor 2 (FGF-2) only increased the number of melanoph ores. The neurite outgrowth induced by NGF was inhibited by the dipept ides blocking the ubiquitin mediated proteolysis (Leu-Ala and Leu-Gly) whereas the inactive control dipeptides (Ala-Leu and Ala-His) had no effect. This suggests that ubiquitin-mediated proteolysis involving th e ubiquitin ligase E3 is necessary for growth factor induced neuronal differentiation during the development of the central nervous system.