Autophagic degradation of an oncoprotein

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Arsenic Trioxide
  • Arsenicals / therapeutic use
  • Autophagy / physiology*
  • Humans
  • Leukemia, Promyelocytic, Acute / drug therapy
  • Leukemia, Promyelocytic, Acute / genetics
  • Leukemia, Promyelocytic, Acute / metabolism
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism*
  • Oxides / therapeutic use
  • Proteasome Endopeptidase Complex / metabolism
  • Tretinoin / therapeutic use


  • Antineoplastic Agents
  • Arsenicals
  • Oncogene Proteins, Fusion
  • Oxides
  • promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
  • Tretinoin
  • Proteasome Endopeptidase Complex
  • Arsenic Trioxide