NDLI: Retinoic acid induces proteasome-dependent degradation of retinoic acid receptor α (RARα) and oncogenic RARα fusion proteins

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Retinoic acid induces proteasome-dependent degradation of retinoic acid receptor α (RARα) and oncogenic RARα fusion proteins

Content Provider	Semantic Scholar
Author	Gianní, Maurizio Kopf, Eliezer Honoré, Nicole Chelbi-Alix, Mounira K. Koken, Marcel H. M. Quignon, Frédérique Rochette-Egly, Cécile
Copyright Year	1999
Abstract	Analyzing the pathways by which retinoic acid (RA) induces promyelocytic leukemia/retinoic acid receptor α (PML/RARα) catabolism in acute promyelocytic leukemia (APL), we found that, in addition to caspase-mediated PML/RARα cleavage, RA triggers degradation of both PML/RARα and RARα. Similarly, in non-APL cells, RA directly targeted RARα and RARα fusions to the proteasome degradation pathway. Activation of either RARα or RXRα by specific agonists induced degradation of both proteins. Conversely, a mutation in RARα that abolishes heterodimer formation and DNA binding, blocked both RARα and RXRα degradation. Mutations in the RARα DNA-binding domain or AF-2 transcriptional activation region also impaired RARα catabolism. Hence, our results link transcriptional activation to receptor catabolism and suggest that transcriptional up-regulation of nuclear receptors by their ligands may be a feedback mechanism allowing sustained target-gene activation.
Starting Page	14807
Ending Page	14812
Page Count	6
File Format	PDF HTM / HTML
DOI	10.1073/pnas.96.26.14807
Alternate Webpage(s)	http://www.pnas.org/content/96/26/14807.full.pdf
Alternate Webpage(s)	https://doi.org/10.1073/pnas.96.26.14807
Volume Number	96
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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