Phosphorylation of PML by mitogen-activated protein kinases plays a key role in arsenic trioxide-mediated apoptosis

Fumihiko Hayakawa, Martin L. Privalsky

Research output: Contribution to journalArticle

108 Scopus citations

Abstract

The promyelocytic leukemia (PML) protein is a potent growth suppressor and proapototic factor, whereas aberrant fusions of PML and retinoic acid receptor (RAR)-α are causal agents in human acute promyelocytic leukemia. Arsenic trioxide (As2O3) treatment induces apoptosis in acute promyelocytic leukemia cells through an incompletely understood mechanism. We report here that As2O3 treatment induces phosphorylation of the PML protein through a mitogen-activated protein (MAP) kinase pathway. Increased PML phosphorylation is associated with increased sumoylation of PML and increased PML-mediated apoptosis. Conversely, MAP kinase cascade inhibitors, or the introduction of phosphorylation or sumoylation-defective mutations of PML, impair As2O3-mediated apoptosis by PML. We conclude that phosphorylation by MAP kinase cascades potentiates the antiproliferative functions of PML and helps mediate the proapoptotic effects of As 2O3.

Original languageEnglish (US)
Pages (from-to)389-401
Number of pages13
JournalCancer Cell
Volume5
Issue number4
DOIs
StatePublished - Apr 2004

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Fingerprint Dive into the research topics of 'Phosphorylation of PML by mitogen-activated protein kinases plays a key role in arsenic trioxide-mediated apoptosis'. Together they form a unique fingerprint.

  • Cite this