FBXO43 promotes cell cycle progression in cancer cells through stabilizing SKP2

  • Cancer Lett. 2024 Apr 9:591:216848. doi: 10.1016/j.canlet.2024.216848.
Liyun Zheng  1 ,  Jiajia Shen  1 ,  Yang Chen  1 ,  Jingyu Lin  1 ,  Pengyu Li  2 ,  Xiaoli Zhao  1 ,  Hangjiang Ren  1 ,  Yi Sun  3 ,  Zhen Wang  4
Affiliations
  • 1. Department of Biochemistry, Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
  • 2. Qilu Hospital of Shan Dong University, Jinan, Shandong Province, China.
  • 3. Cancer Institute of the Second Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang University Cancer Center, Hangzhou, China; Research Center for Life Science and Human Health, Beijing Institute of Zhejiang University, Hangzhou, China. Electronic address: [email protected].
  • 4. Department of Biochemistry, Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. Electronic address: [email protected].
PMID: 38604312 DOI: 10.1016/j.canlet.2024.216848
Abstract

FBXO43 is a member of the FBXO subfamily of F-box proteins, known to be a regulatory hub during meiosis. A body of data showed that FBXO43 is overexpressed in a number of human cancers. However, whether and how FBXO43 affects cell cycle progression and growth of Cancer cells remain elusive. In this study, we provide first piece of evidence, showing a pivotal role of FBXO43 in cell cycle progression and growth of Cancer cells. Specifically, FBXO43 acts as a positive cell cycle regulator with an oncogenic activity in variety types of human Cancer, including non-small cell lung Cancer, hepatocellular carcinoma and sarcoma. Mechanistically, FBXO43 interacts with phosphorylated SKP2 induced by Akt1, leading to reduced SKP2 auto-ubiquitylation and subsequent Proteasome degradation. Taken together, our study demonstrates that FBXO43 promotes cell cycle progression by stabilizing SKP2, and FBXO43 could serve as a potential anti-cancer target.

Keywords
Cancer; Cell cycle; FBXO43; SKP2; Ubiquitylation.
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