CK2 mediates phosphorylation and ubiquitin-mediated degradation of the PML tumor suppressor

Pier P. Scaglioni, T. M. Yung, S. C. Choi, C. Baldini, G. Konstantinidou, P. P. Pandolfi

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

The PML tumor suppressor controls growth suppression, induction of apoptosis, and cellular senescence. PML loss occurs frequently in hematopoietic and solid tumors. PML loss often correlates with tumor progression. Casein kinase 2 (CK2) is a stress-activated serine/ threonine protein kinase that is oncogenic and frequently overexpressed in human tumor of multiple histological origins. In addition, CK2 overexpression due to gene amplification has been reported to be an adverse prognostic factor in non-small cell lung cancer. At the 5th International Conference on Protein Kinase CK2 in Padova, Italy, we reviewed our recent findings that PML undergoes ubiquitin/ proteasome-mediated degradation in immortalized and tumor derived cell lines. PML degradation depends on direct CK2 phosphorylation of PML Ser517. PML mutants that are resistant to CK2 phosphorylation display increased tumor suppressive functions in assays measuring apoptosis, replicative senescence, and in xenograft models. More significantly, CK2 pharmacological inhibition enhances PML tumor suppressive property. These data identify a key post-translational mechanism that controls PML protein levels in cancer cells and suggest that CK2 inhibitors may be beneficial anti-cancer drugs.

Original languageEnglish (US)
Pages (from-to)149-154
Number of pages6
JournalMolecular and Cellular Biochemistry
Volume316
Issue number1-2
DOIs
StatePublished - Jan 1 2008

Keywords

  • CK2
  • Lung cancer pathogenesis
  • PML
  • Protein polyubiquitination

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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    Scaglioni, P. P., Yung, T. M., Choi, S. C., Baldini, C., Konstantinidou, G., & Pandolfi, P. P. (2008). CK2 mediates phosphorylation and ubiquitin-mediated degradation of the PML tumor suppressor. Molecular and Cellular Biochemistry, 316(1-2), 149-154. https://doi.org/10.1007/s11010-008-9812-7