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Molecular mechanism of CCDC106 regulating the p53-Mdm2/MdmX signaling axis

Ting Zhou1,2, Zhiqiang Ke2,3, Qianqian Ma2

  • 1School of Light Industry and Food Engineering, Guangxi University, No. 100, Daxuedong Road, Xixiangtang District, Nanning, 530004, Guangxi, China.

Scientific Reports
|December 11, 2023
PubMed

Insights

The coiled-coil domain-containing protein 106 (CCDC106) regulates the p53 tumor suppressor pathway by interacting with p53 and competing with Mdm2/MdmX. This interaction influences the cellular levels of p53, Mdm2, and MdmX, impacting cancer development.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Signaling

Background:

  • The tumor suppressor p53 (p53) is crucial for maintaining genomic stability.
  • p53 levels and activity are tightly regulated by murine double minute 2 (Mdm2) and MdmX.
  • Dysregulation of the p53-Mdm2/MdmX axis is implicated in cancer development.

Purpose of the Study:

  • To elucidate the molecular mechanism of interaction between p53, Mdm2, MdmX, and CCDC106.
  • To investigate the role of coiled-coil domain-containing protein 106 (CCDC106) in regulating the p53 signaling pathway.

Main Methods:

  • Investigated protein-protein interactions.
  • Assessed the impact of CCDC106 on cellular levels of p53, Mdm2, and MdmX.
  • Studied the competitive binding of CCDC106 with Mdm2 and MdmX to p53.

Main Results:

  • CCDC106 directly interacts with the transactivation domain of p53.
  • CCDC106 competes with Mdm2 and MdmX for binding to p53.
  • CCDC106 overexpression leads to decreased levels of p53, Mdm2, and MdmX; conversely, decreased p53 reduces CCDC106 levels.

Conclusions:

  • CCDC106 acts as a signaling regulator of the p53-Mdm2/MdmX axis.
  • CCDC106 modulates the cellular homeostasis of p53 and its negative regulators.
  • Understanding this regulatory mechanism offers insights into potential cancer therapeutic strategies targeting the p53 pathway.

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