FBXO43 promotes cell cycle progression in cancer cells through stabilizing SKP2.
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.
Mesh Terms:
Animals, Carcinoma, Non-Small-Cell Lung, Cell Cycle, Cell Line, Tumor, Cell Proliferation, F-Box Proteins, Gene Expression Regulation, Neoplastic, HEK293 Cells, Humans, Lung Neoplasms, Mice, Neoplasms, Phosphorylation, Proteasome Endopeptidase Complex, Proteolysis, Proto-Oncogene Proteins c-akt, S-Phase Kinase-Associated Proteins, Ubiquitination
Animals, Carcinoma, Non-Small-Cell Lung, Cell Cycle, Cell Line, Tumor, Cell Proliferation, F-Box Proteins, Gene Expression Regulation, Neoplastic, HEK293 Cells, Humans, Lung Neoplasms, Mice, Neoplasms, Phosphorylation, Proteasome Endopeptidase Complex, Proteolysis, Proto-Oncogene Proteins c-akt, S-Phase Kinase-Associated Proteins, Ubiquitination
Cancer Lett
Date: Jun. 01, 2024
PubMed ID: 38604312
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