The viral and cellular Rel oncoproteins induce the differentiation of P19 embryonal carcinoma cells.

Rel proteins have been implicated in the differentiation and transformation of lymphoid cells. Despite their significant sequence homology to the Drosophila Dorsal morphogen, a functional role for Rel proteins in early development has yet to be established. Here we show that expression of the v- or c-rel genes in P19 embryonal carcinoma (EC) cells leads to drastic morphological changes accompanied by the expression of several differentiation-specific antigens. In contrast, v-Rel mutants defective for DNA-binding as well as those lacking the F9 cell-specific transcription activation region of v-Rel were equally unable to promote P19 cell differentiation. Our results demonstrate that transcriptional activation by Rel proteins correlates with Rel-induced differentiation of EC cells, and raise the intriguing possibility that Rel proteins may play an important role in early developmental processes.