| First Author | Scaglioni PP | Year | 2006 |
| Journal | Cell | Volume | 126 |
| Issue | 2 | Pages | 269-83 |
| PubMed ID | 16873060 | Mgi Jnum | J:144680 |
| Mgi Id | MGI:3831499 | Doi | 10.1016/j.cell.2006.05.041 |
| Citation | Scaglioni PP, et al. (2006) A CK2-dependent mechanism for degradation of the PML tumor suppressor. Cell 126(2):269-83 |
| abstractText | 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. |
