Participation of P53 family proteins in the oligodendroglial differentiation regulation by the ubiquitin-proteasome system

C. A. CALATAYUD, E. F. SOTO, J. M. PASQUINI AND L. A. PASQUINI

Portland, Oregan

Congreso; thirty-Seventh Annual Meeting; 2006

American Society of Neurochemistry

We studied the possible relationship between ubiquitin-proteasome (UbP) system and oligodendroglial lineage development. Previously we demonstrated that addition of lactacystin (L), a specific proteasome inhibitor, at low concentrations, to primary cultures of oligodendrocytes (OLGcs) produced their withdrawal from the cell cycle and induced their differentiation. Additionally, we demonstrated in the N20.1 cell line, that a decrease in proteasome activity enhances MBP promoter activity by stabilization of Sp1 and p27. Recent studies demonstrate the participation of p53 proteins family in OLGcs maturation. Turnover of these proteins is regulated by the Ub-P system. Western blot analysis in the N19 cell line, suggest that p53 is present when the cells proliferate or at early stages of differentiation. Transfection of the N19 cell line by electroporation shows that GFP-p53 expression is increased when the cells proliferate and the treatment with lactacystin increases even more GFP-p53 levels. Our results would suggest that the differentiation observed in the presence of L could be mediated, at least in part, by p53 stabilization and its participation in the onset of the differentiation program.