A CK2-Dependent Mechanism for Degradation of the PML Tumor Suppressor

Pier Paolo Scaglioni, Thomas M. Yung, Lu Fan Cai, Hediye Erdjument-Bromage, Andrew J. Kaufman, Bhuvanesh Singh, Julie Teruya-Feldstein, Paul Tempst, Pier Paolo Pandolfi

Research output: Contribution to journalArticlepeer-review

257 Scopus citations


The PML tumor suppressor controls key pathways for growth suppression, induction of apoptosis, and cellular senescence. PML loss occurs frequently in human tumors through unknown posttranslational mechanisms. Casein kinase 2 (CK2) is oncogenic and frequently upregulated in human tumors. Here we show that CK2 regulates PML protein levels by promoting its ubiquitin-mediated degradation dependent on direct phosphorylation at Ser517. Consequently, PML mutants that are resistant to CK2 phosphorylation display increased tumor-suppressive functions. In a faithful mouse model of lung cancer, we demonstrate that Pml inactivation leads to increased tumorigenesis. Furthermore, CK2 pharmacological inhibition enhances the PML tumor-suppressive property in vivo. Importantly, we found an inverse correlation between CK2 kinase activity and PML protein levels in human lung cancer-derived cell lines and primary specimens. These data identify a key posttranslational mechanism that controls PML protein levels and provide therapeutic means toward PML restoration through CK2 inhibition.

Original languageEnglish (US)
Pages (from-to)269-283
Number of pages15
Issue number2
StatePublished - Jul 28 2006

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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