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.