The role of wild-type p53 in the differentiation of primary hemopoietic and muscle cells

Experiments previously performed on 32D and C2C12 cell lines indicated that wild type p53 (wtp53) protein has a role in granulocyte and myotube differ entiation. Since these are immortal cells, we asked whether the inhibition of differentiation induced by the expression of dominant-negative p53 (dnp5 3) proteins was dependent on the immortalization-determined microenvironmen t. Thus, we evaluated the effects produced by interfering with the endogeno us p53 gene in murine primary hemopoietic and muscle cells. Expression of d np53 protein reduced the differentiation of bone marrow cells into granuloc ytes and macrophages. Moreover, p53 activation was measurable during the di fferentiation process of primary myoblasts, while interference with this ac tivation led to a consistent slow down of terminal differentiation. Since t he impairment of the differentiation was not accompanied by alterations in the cell cycle withdrawal and in the rate of apoptosis which are coupled wi th these types of differentiation, the data here reported support a specifi c role for p53 in the differentiation process. However, the difference in t he intensity of inhibition between immortal and primary cells, i.e., comple te versus slow down, respectively, suggests that the immortalization proces s might render the cells more sensitive to the loss of wtp53 activity for t he differentiation process.