Death by arsenic: implications of PML sumoylation

Cancer Cell. 2004 Apr;5(4):307-9. doi: 10.1016/s1535-6108(04)00089-3.

Abstract

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.

Publication types

  • Editorial
  • Research Support, Non-U.S. Gov't
  • Comment

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Arsenic Trioxide
  • Arsenicals / pharmacology*
  • Humans
  • Leukemia, Promyelocytic, Acute / pathology
  • MAP Kinase Signaling System*
  • Neoplasm Proteins / metabolism*
  • Nuclear Proteins*
  • Oxides / pharmacology*
  • Phosphorylation
  • Promyelocytic Leukemia Protein
  • Transcription Factors / metabolism*
  • Tumor Suppressor Proteins

Substances

  • Arsenicals
  • Neoplasm Proteins
  • Nuclear Proteins
  • Oxides
  • Promyelocytic Leukemia Protein
  • Transcription Factors
  • Tumor Suppressor Proteins
  • PML protein, human
  • Arsenic Trioxide