Molecular and Cellular Biochemistry

, Volume 316, Issue 1, pp 149–154

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

  • P. P. Scaglioni
  • T. M. Yung
  • S. C. Choi
  • C. Baldini
  • G. Konstantinidou
  • P. P. Pandolfi
Article

DOI: 10.1007/s11010-008-9812-7

Cite this article as:
Scaglioni, P.P., Yung, T.M., Choi, S.C. et al. Mol Cell Biochem (2008) 316: 149. doi:10.1007/s11010-008-9812-7
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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.

Keywords

CK2PMLProtein polyubiquitinationLung cancer pathogenesis

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • P. P. Scaglioni
    • 1
  • T. M. Yung
    • 2
  • S. C. Choi
    • 1
  • C. Baldini
    • 1
  • G. Konstantinidou
    • 1
  • P. P. Pandolfi
    • 3
    • 4
  1. 1.Division of Hematology-OncologyUniversity of Texas Southwestern Medical CenterDallasUSA
  2. 2.Cancer Biology and Genetics Program, Sloan-Kettering InstituteMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  3. 3.Cancer Genetics Program, Beth Israel Deaconess Cancer CenterHarvard Medical SchoolBostonUSA
  4. 4.Department of Medicine, Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonUSA