Autophagic degradation of an oncoprotein.
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.
Bøe
Stig Ove
SO
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
Simonsen
Anne
A
D000970:Antineoplastic Agents / Q000627:therapeutic use; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use; D001343:Autophagy / Q000502:physiology*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D010087:Oxides / Q000627:therapeutic use; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D014212:Tretinoin / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001152:Arsenicals; D015514:Oncogene Proteins, Fusion; D010087:Oxides; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin; D046988:Proteasome Endopeptidase Complex; D000077237:Arsenic Trioxide