DIFFERENTIAL SUBCELLULAR P53 LOCALIZATION AND FUNCTION IN N-TYPE AND S-TYPE NEUROBLASTOMA CELL-LINES

Neuroblastoma (NB) cells in vitro are capable of bidirectional transdi fferentiation, resulting in two distinct, yet reversible, phenotypes o f neuroblastic (N-type) and nonneuronal (S-type) Schwann-like cells. O ur previous studies suggested that the wild-type p53 protein is subjec t to differential regulation in a subset of neuronal cell types. To fu rther test this hypothesis, we compared p53 function in three matched pairs of N- and S-type cell lines, each pair originating from an indiv idual NE tumor. Our data show that although p53 remains cytoplasmicall y sequestered in a punctate pattern in N-type cells after DNA damage, the protein is diffusely distributed in the S-type cells and is additi onally capable of translocating to the nucleus and mediating a biologi cal response to this damage. Our data,therefore, suggest that the p53 protein may be differentially regulated by a neuronal cellular environ ment and that the sequestration of p53 in NE may be reversible.