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Activation of protein kinase CK2 attenuates FOXO3a functioning in a PML-dependent manner: implications in human

A Chatterjee1, U Chatterjee, M K Ghosh

  • 1Division of Cancer Biology and Inflammatory Disorder, CSIR-Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata 700032, India.

Cell Death & Disease
|March 16, 2013
PubMed

Insights

Dereguated Protein Kinase CK2 (Caseine Kinase II) promotes cancer by degrading the tumor suppressor PML (promyelocytic leukemia). This leads to the inactivation of FOXO3a, a key suppressor of tumor growth.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Signaling

Background:

  • Protein kinase CK2 (CK2) is crucial for cell growth and proliferation, and its deregulation is linked to cancer.
  • CK2 phosphorylates and degrades the tumor suppressor PML (promyelocytic leukemia), hindering its anti-cancer functions.
  • PML normally suppresses tumors by maintaining nuclear active AKT (pAKT) and stabilizing FOXO3a.

Purpose of the Study:

  • To elucidate a novel signaling axis involving CK2, PML, and FOXO3a in cancer progression.
  • To identify PHLPP2 as a novel nuclear interacting partner of PML.

Main Methods:

  • Investigated the interaction between PML and PHLPP2 within the nucleus.
  • Analyzed the impact of CK2 deregulation on the PML-PHLPP2 complex.
  • Assessed the downstream effects on nuclear pAKT, FOXO3a, and target genes like p21, p27, and Bim.

Main Results:

  • Discovered that deregulated CK2 disrupts the PML-PHLPP2 association.
  • Demonstrated that PML degradation and pAKT stabilization are critical steps in this pathway.
  • Showed that this axis leads to nuclear exclusion and inactivation of FOXO3a, downregulating tumor suppressors.

Conclusions:

  • A novel signaling axis driven by deregulated CK2 promotes cancer by inactivating FOXO3a.
  • Targeting CK2 or modulating the PML-PHLPP2 interaction could offer therapeutic strategies against cancer.

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