Retinoic acid induces the degradation of the leukemogenic protein encoded by the promyelocytic leukemia gene fused to the retinoic acid receptor alpha gene.
Acute promyelocytic leukemia (APL) cells carry a mutated gene that is the result of a translocation in which the retinoic acid receptor alpha (RAR alpha) gene is fused to the promyelocytic leukemia (PML) gene, coding for a fusion protein, PML/RAR alpha. Its presence is the single event that causes APL in transgenic mice. All-trans-retinoic acid (atRA) induces the proteolytic degradation of PML/RAR alpha by ubiquitination and proteolysis. RAR alpha itself is also degraded by atRA treatment, a process representing a possible feedback mechanism to turn off RAR alpha's stimulation of transcription.
Wolf
G
G
Department of Nutritional Sciences, University of California, Berkeley 94720-3104, USA.
Smas
C M
CM
D000970:Antineoplastic Agents / Q000494:pharmacology; D019677:Artificial Gene Fusion; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology / Q000502:physiology*; D025521:Tumor Suppressor Proteins; D014801:Vitamin A / Q000627:therapeutic use
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D018168:Receptors, Retinoic Acid; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014801:Vitamin A; C070576:PML protein, human; D014212:Tretinoin