Retinoid receptors in development and disease.
Nuclear receptors comprise a large family of ligand-dependent transcription factors that display considerable specificity in and selectivity in regulating the genetic programs they ultimately influence. The response to retinoic acid (RA) is mediated by two families of transcription factors which include the retinoic acids receptors (RARs) and the retinoid X receptors (RXRs). In human acute promyelocytic leukemia (APL), RAR alpha becomes an activated oncogene as a consequence of its fusion to the PML locus. Because patients with APL can be induced into remission with high dose RA therapy, we propose that PML-RAR is a new class of dominant negative oncogene that disrupts a structure that includes at least five other proteins. This mega-complex, referred to as a "POD", is disrupted in leukemic cells expressing the oncoprotein and is reassembled following high dose RA therapy in both cell culture an in patients.
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D000375:Aging; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D004330:Drosophila; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D008957:Models, Genetic; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D009857:Oncogenes; D000071156:Promyelocytic Leukemia Protein; D018168:Receptors, Retinoic Acid / Q000235:genetics* / Q000378:metabolism; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D014212:Tretinoin