A dominant negative mutation of the alpha retinoic acid receptor gene in a retinoic acid-nonresponsive embryonal carcinoma cell.
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 (RAR alpha). The mutant gene encodes a protein, RAR alpha', that has lost its 70 C-terminal amino acids, thus truncating the RA-binding domain. The RAR alpha' was found to be a dominant repressor of transcription from an RA-responsive target gene; however, expression of RAR alpha' was insufficient to confer RA nonresponsiveness, suggesting that RAC65 cells carry an additional mutation(s) affecting RA-induced genes.
Pratt
M A
MA
Department of Medicine, University of Ottawa, Ontario, Canada.
Kralova
J
J
McBurney
M W
MW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000235:genetics*; D002454:Cell Differentiation; D002460:Cell Line; D004273:DNA, Neoplasm / Q000235:genetics; D004351:Drug Resistance; D015723:Gene Library; D005796:Genes; D005799:Genes, Dominant; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics; D018168:Receptors, Retinoic Acid; D013724:Teratoma / Q000235:genetics*; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology
D002352:Carrier Proteins; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D014212:Tretinoin