CK2 mediates phosphorylation and ubiquitin-mediated degradation of the PML tumor suppressor Journal Article
| Authors: | Scaglioni, P. P.; Yung, T. M.; Choi, S.; Baldini, C.; Konstantinidou, G.; Pandolfi, P. P. |
| Article Title: | CK2 mediates phosphorylation and ubiquitin-mediated degradation of the PML tumor suppressor |
| 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. © Springer Science+Business Media, LLC. 2008. |
| Keywords: | protein phosphorylation; mutation; nonhuman; ubiquitin; animals; mice; apoptosis; proteasome endopeptidase complex; mitogen activated protein kinase p38; protein degradation; lung non small cell cancer; carcinoma, non-small-cell lung; lung neoplasms; antineoplastic activity; enzyme activation; tumor xenograft; enzyme activity; cell line, tumor; phosphorylation; carcinogenesis; transcription factors; nuclear proteins; protein kinase inhibitors; cancer inhibition; protein processing; ubiquitination; amino acid sequence; molecular sequence data; protein processing, post-translational; mice, nude; tumor suppressor proteins; thermodynamics; senescence; tumor; tumor suppressor protein; cell stress; growth inhibition; pml; p38 mitogen-activated protein kinases; ck2; lung cancer pathogenesis; protein polyubiquitination; casein kinase ii; emodin; promyelocytic leukemia tumor suppressor protein; osmotic stress |
| Journal Title: | Molecular and Cellular Biochemistry |
| Volume: | 316 |
| Issue: | 1-2 |
| ISSN: | 0300-8177 |
| Publisher: | Springer |
| Date Published: | 2008-09-01 |
| Start Page: | 149 |
| End Page: | 154 |
| Language: | English |
| DOI: | 10.1007/s11010-008-9812-7 |
| PUBMED: | 18566754 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 6" - "Export Date: 17 November 2011" - "CODEN: MCBIB" - "Source: Scopus" |
