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CK2 functionally interacts with AKT/PKB to promote the β-catenin-dependent expression of survivin and enhance cell survival

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Abstract

β-Catenin is crucial in the canonical Wnt signaling pathway. This pathway is up-regulated by CK2 which is associated with an enhanced expression of the antiapoptotic protein survivin, although the underlying molecular mechanism is unknown. AKT/PKB kinase phosphorylates and promotes β-catenin transcriptional activity, whereas CK2 hyperactivates AKT by phosphorylation at Ser129; however, the role of this phosphorylation on β-catenin transcriptional activity and cell survival is unclear. We studied in HEK-293T cells, the effect of CK2-dependent hyperactivation of AKT on cell viability, as well as analyzed β-catenin subcellular localization and transcriptional activity and survivin expression. CK2α overexpression led to an augmented β-catenin-dependent transcription and protein levels of survivin, and consequently an enhanced resistance to apoptosis. However, CK2α-enhancing effects were reversed when an AKT mutant deficient in Ser129 phosphorylation by CK2 was co-expressed. Therefore, our results strongly suggest that CK2α-specific enhancement of β-catenin transcriptional activity as well as cell survival may depend on AKT hyperactivation by CK2.

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Abbreviations

CK2:

Acronym for the former name casein kinase II

CK2α:

CK2’s catalytic subunit α

Tcf/Lef:

T-cell factor/lymphoid enhancer binding factor

DMAT:

2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole

TBB:

4,5,6,7-tetrabromobenzotriazole

IAP:

Inhibitor of apoptosis protein

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Acknowledgments

The authors thank Maria Ruzzene (University of Padova, Italy) and Angela Barth (Stanford University, USA) for providing the plasmids encoding AKT-S129A and GFP-β-catenin, respectively. The authors also wish to thank Gonzalo Cabrera (ICBM) for his assistance in the epifluorescence microscopy. This study was supported by the Fondecyt grant numbers 15010006 (K.M., R.A. & J.C.T.), 1095234 (M.G. & J.C.T.), and 11070116 (J.C.T.).

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Authors and Affiliations

  1. Institute of Biomedical Sciences (ICBM), Cell Transformation Laboratory, Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Av. Independencia 1027, 8700664, Santiago, Chile

    Daniela P. Ponce, Roger Yefi, Pablo Cabello, Jose L. Maturana, Ignacio Niechi, Eduardo Silva, Mario Galindo, Marcelo Antonelli & Julio C. Tapia

  2. Center for Molecular Studies of the Cell (CEMC), Faculty of Medicine, University of Chile, Santiago, Chile

    Katherine Marcelain, Ricardo Armisen & Julio C. Tapia

Authors
  1. Daniela P. Ponce
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  2. Roger Yefi
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  3. Pablo Cabello
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  4. Jose L. Maturana
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  5. Ignacio Niechi
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  6. Eduardo Silva
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  7. Mario Galindo
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  8. Marcelo Antonelli
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  9. Katherine Marcelain
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  10. Ricardo Armisen
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  11. Julio C. Tapia
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Corresponding author

Correspondence to Julio C. Tapia.

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Ponce, D.P., Yefi, R., Cabello, P. et al. CK2 functionally interacts with AKT/PKB to promote the β-catenin-dependent expression of survivin and enhance cell survival. Mol Cell Biochem 356, 127–132 (2011). https://doi.org/10.1007/s11010-011-0965-4

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  • DOI: https://doi.org/10.1007/s11010-011-0965-4

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