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 proteolysis has been examined on growth factor induced neurite outgrowth from amphibian neuroepithelial precursor cells in primary culture. Nerve growth factor (NGF) stimulated neuritogenesis from these cells but fibroblast growth factor 2 (FGF-2) only increased the number of melanophores. The neurite outgrowth induced by NGF was inhibited by the dipeptides 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 the ubiquitin ligase E3 is necessary for growth factor induced neuronal differentiation during the development of the central nervous system.