title: Autophagic degradation of an oncoprotein.
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.
authors: 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
authors: Stig Ove
authors: SO
authors: Bøe
authors: Anne
authors: A
authors: Simonsen
mesh_terms: 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
chemical_list: 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