Death by arsenic: implications of PML sumoylation.
PML is a multifunctional protein that plays an important role in programmed cell death, albeit by mechanisms that remain unclear. In this issue of Cancer Cell, Hayakawa and Privalsky associate a MAP kinase pathway that mediates As(2)O(3)-induced PML phosphorylation with sumoylation and increased apoptotic activity of PML. Thus, specific MAP kinases may potentiate apoptosis in response to As(2)O(3), a compound that has dramatic activity against acute promyelocytic leukemia (APL) cells. This novel mechanism may have important implications for use of As(2)O(3) as a chemotherapeutic agent, especially in malignancies less sensitive to As(2)O(3) than APL.
Mann
Koren K
KK
Lady Davis Institute for Medical Research at the S.M.B.D. Jewish General Hospital, McGill University, 3755 Cote Ste. Catherine Road, Montreal, Quebec H3T 1E2, Canada.
Miller
Wilson H
WH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology; D020935:MAP Kinase Signaling System; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins; D010087:Oxides / Q000494:pharmacology*; D010766:Phosphorylation; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D001152:Arsenicals; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010087:Oxides; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D000077237:Arsenic Trioxide