Polo-like kinase 1 phosphorylates and regulates Bcl-x(L) during pironetin-induced apoptosis

Oncogene. 2009 Jan 8;28(1):107-16. doi: 10.1038/onc.2008.368. Epub 2008 Sep 29.

Abstract

Bcl-x(L), an anti-apoptotic Bcl-2 family member protein, contributes to the resistance against chemotherapies such as tubulin-binder treatment in many human tumors. Although Bcl-x(L) is phosphorylated after tubulin-binder treatment, the role of the phosphorylation and its responsible kinase(s) are poorly understood. Here, we identified Plk1 (polo-like kinase 1) as a Bcl-x(L) kinase. Same location of Bcl-x(L) and Plk1 was revealed by immunocytochemical analyses at M-phase in situ. Plk1 phosphorylates Bcl-x(L) in vitro, and we identified Plk1 phosphorylation sites in Bcl-x(L). When all of these phosphorylation sites were substituted to alanines, the anti-apoptotic activity of the Bcl-x(L) mutant against the apoptosis induced by pironetin, but not against ultraviolet-induced apoptosis, was increased. These observations suggest that Plk1 is a regulator of Bcl-x(L) phosphorylation and controls the anti-apoptotic activity of Bcl-x(L) during pironetin-induced apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / genetics
  • Alanine / metabolism
  • Apoptosis*
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Humans
  • Mutation
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Pyrones / pharmacology
  • Serine / metabolism
  • bcl-X Protein / genetics
  • bcl-X Protein / metabolism*

Substances

  • Cell Cycle Proteins
  • Proto-Oncogene Proteins
  • Pyrones
  • bcl-X Protein
  • pironetin
  • Serine
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1
  • Alanine