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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. et al. Nutr Rev 2000 Jul;58(7):211-4.





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