FBXO22 degrades nuclear PTEN to promote tumorigenesis

Meng-Kai Ge, Na Zhang, Li Xia, Cheng Zhang, Shuang-Shu Dong, Zhan-Ming Li, Yan Ji, Min-Hua Zheng, Jing Sun, Guo-Qiang Chen () and Shao-Ming Shen ()
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Meng-Kai Ge: Shanghai Jiao Tong University School of Medicine
Na Zhang: Shanghai Jiao Tong University School of Medicine
Li Xia: Shanghai Jiao Tong University School of Medicine
Cheng Zhang: Shanghai Jiao Tong University School of Medicine
Shuang-Shu Dong: Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Zhan-Ming Li: Shanghai Jiao Tong University School of Medicine
Yan Ji: Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Min-Hua Zheng: Shanghai Jiao Tong University School of Medicine
Jing Sun: Shanghai Jiao Tong University School of Medicine
Guo-Qiang Chen: Shanghai Jiao Tong University School of Medicine
Shao-Ming Shen: Shanghai Jiao Tong University School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract Nuclear localization of PTEN is essential for its tumor suppressive role, and loss of nuclear PTEN is more prominent than cytoplasmic PTEN in many kinds of cancers. However, nuclear PTEN-specific regulatory mechanisms were rarely reported. Based on the finding that nuclear PTEN is more unstable than cytoplasmic PTEN, here we identify that F-box only protein 22 (FBXO22) induces ubiquitylation of nuclear but not cytoplasmic PTEN at lysine 221, which is responsible for the degradation of nuclear PTEN. FBXO22 plays a tumor-promoting role by ubiquitylating and degrading nuclear PTEN. In accordance, FBXO22 is overexpressed in various cancer types, and contributes to nuclear PTEN downregulation in colorectal cancer tissues. Cumulatively, our study reports the mechanism to specifically regulate the stability of nuclear PTEN, which would provide the opportunity for developing therapeutic strategies aiming to achieve complete reactivation of PTEN as a tumor suppressor.

Date: 2020
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DOI: 10.1038/s41467-020-15578-1

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