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Autophagy. 2010 Oct;6(7):964-5. doi: 10.4161/auto.6.7.13066. Epub 2010 Oct 19.

Autophagic degradation of an oncoprotein.

Author information

1
Centre for Molecular Biology and Neuroscience (CMBN) and Institute of Medical Microbiology, Rikshospitalet University Hospital, and Institute of Clinical Biochemistry, University of Oslo, Oslo, Norway. stig.ove.boe@rr-research.no

Abstract

Acute promyelocytic leukemia (APL) is characterized by a chromosomal t(15;17) translocation that fuses the gene encoding the promyelocytic leukemia protein (PML) to that encoding retinoic acid receptor alpha (RARA). The product of this genetic aberration, the PML/RARA fusion protein, is highly oncogenic and supports malignant transformation and growth of hematopoietic precursor cells at the promyelocytic stage of differentiation. Successful treatment of APL by all-trans retinoic acid (ATRA) or arsenic trioxide (ATO) depends on the ability of these drugs to induce proteolytic degradation of this chimeric protein. In a recently published study we demonstrate that PML/RARA is amenable for degradation by autophagy and that ATRA- and ATO-induced PML/RARA degradation is autophagy-dependent. Consequently, autophagic degradation regulates basal turnover as well as therapy-induced elimination of this oncoprotein. In addition, our study reveals an important role of autophagy in promoting granulocytic differentiation of APL cells.

PMID:
20724820
DOI:
10.4161/auto.6.7.13066
[Indexed for MEDLINE]

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