A Dominant Negative Mutation of the Alpha Retinoic Acid Receptor Gene in a Retinoic Acid-Nonresponsive Embryonal Carcinoma Cell

Abstract

Pluripotential embryonal carcinoma cells such as those of the P19 line differentiate when exposed to retinoic acid (RA). The RAC65 cell line is a mutant clone of P19 cells selected to be RA nonresponsive. RAC65 cells carry a rearrangement affecting one of the genes encoding a nuclear retinoic acid receptor (RARα). The mutant gene encodes a protein, RARα', that has lost its 70 C-terminal amino acids, thus truncating the RA-binding domain. The RARα' was found to be a dominant repressor of transcription from an RA-responsive target gene; however, expression of RARα' was insufficient to confer RA nonresponsiveness, suggesting that RAC65 cells carry an additional mutation(s) affecting RA-induced genes.