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

The tumor suppressor p53 (p53) is regulated by murine double minute 2 (Mdm2) and its homologous MdmX in maintaining the basal level of p53. Overexpressed Mdm2/MdmX inhibits cellular p53 activity, which is highly relevant to cancer occurrence. Coiled-coil domain-containing protein 106 (CCDC106) has been identified as a p53-interacting partner. However, the molecular mechanism of the p53/Mdm2/MdmX/CCDC106 interactions is still elusive. Here, we show that CCDC106 functions as a signaling regulator of the p53-Mdm2/MdmX axis. We identified that CCDC106 directly interacts with the p53 transactivation domain by competing with Mdm2 and MdmX. CCDC106 overexpression downregulates the cellular level of p53 and Mdm2/MdmX, and decreased p53 reversibly downregulates the cellular level of CCDC106. Our work provides a molecular mechanism by which CCDC106 regulates the cellular levels of p53 and Mdm2/MdmX. © 2023. The Author(s).

Citation

Ting Zhou, Zhiqiang Ke, Qianqian Ma, Jiani Xiang, Meng Gao, Yongqi Huang, Xiyao Cheng, Zhengding Su. Molecular mechanism of CCDC106 regulating the p53-Mdm2/MdmX signaling axis. Scientific reports. 2023 Dec 11;13(1):21892

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PMID: 38081879

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