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Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach
11:11

Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach

Published on: February 21, 2019

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CK2-mediated CCDC106 phosphorylation is required for p53 degradation in cancer progression

Yichong Ning1,2, Chunqing Wang1,2,3, Xin Liu1,2,4

  • 1State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha, 410081, Hunan, China.

Journal of Experimental & Clinical Cancer Research : CR
|March 20, 2019
PubMed
Abstract

Insights

Dysfunctional p53 protein is linked to cancer. This study identifies a CK2/CCDC106/p53 signaling pathway promoting breast and cervical cancer progression, offering a potential new therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • p53 protein dysfunction is a critical driver of cancer development.
  • CCDC106 protein has been implicated in reducing p53 stability and is associated with lung cancer.
  • The specific roles of CCDC106 in other cancer types and its upstream regulatory mechanisms remain largely unexplored.

Purpose of the Study:

  • To investigate the role of CCDC106 in breast and cervical cancers.
  • To identify upstream regulators of CCDC106.
  • To elucidate the molecular mechanisms by which CCDC106 influences cancer progression and p53 stability.

Main Methods:

  • In vitro kinase assays and Western blotting were used to analyze protein phosphorylation.
  • Co-immunoprecipitation and GST-pulldown assays were employed to determine protein interactions.
  • Functional assays included cell viability, apoptosis, colony formation, migration, and invasion assays. In vivo studies utilized a xenograft mouse model.

Main Results:

  • CCDC106 knockdown stabilized p53, enhancing apoptosis and suppressing proliferation, migration, and invasion in cervical and breast cancer cells with wild-type p53 (wtp53).
  • Overexpression of CCDC106 had opposing effects. CCDC106 did not affect p53-mutant cancer cells.
  • CK2 phosphorylates CCDC106 at Ser-130 and Ser-147, which is crucial for its interaction with p53 and nuclear localization, respectively. Inhibition of this phosphorylation abrogated CCDC106's oncogenic functions.
  • Wild-type CCDC106 promoted tumor growth and p53 degradation in vivo. Suppression of CCDC106 increased sensitivity to the CK2 inhibitor CX-4945.

Conclusions:

  • A novel CK2/CCDC106/p53 signaling axis was identified, playing a significant role in the progression of breast and cervical cancers.
  • This signaling pathway represents a potential therapeutic target for treating these cancers.
  • Targeting CCDC106 or its upstream regulators may enhance the efficacy of existing cancer therapies.
Keywords:
Breast cancerCCDC106Cervical cancerProtein kinase CK2p53

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