Function and regulation of F‑box/WD repeat‑containing protein 7 (Review)

• Published in: Oncology letters Vol. 20; no. 2; pp. 1526 - 1534
• Main Authors: Zhang, Zheng, Hu, Qiangsheng, Xu, Wenyan, Liu, Wensheng, Liu, Mengqi, Sun, Qiqing, Ye, Zeng, Fan, Guixiong, Qin, Yi, Xu, Xiaowu, Yu, Xianjun, Ji, Shunrong
• Format: Journal Article
• Language: English
• Published: Athens Spandidos Publications 01.08.2020; Spandidos Publications UK Ltd; D.A. Spandidos
• Subjects: Amino acids; Apoptosis; Breast cancer; Cell cycle; Cellular signal transduction; Colorectal cancer; Deoxyribonucleic acid; DNA; Epigenetics; Gene mutation; Genetic aspects; Genomes; Kinases; Leukemia; Localization; Metastasis; MicroRNAs; Mutation; Oncology; Pancreatic cancer; Post-translational modifications; Proteins; Review; Signal transduction; Testes; Transcription (Genetics); Tumors; Ubiquitin
• ISSN: 1792-1074; 1792-1082
• DOI: 10.3892/ol.2020.11728

The ubiquitin-proteasome system is an important post-translational modification system involved in numerous biological processes, such as cell cycle regulation, gene transcription, signal transduction, apoptosis, differentiation and development. F-box/WD repeat-containing protein 7 (FBXW7) is one of the most studied F-box (FBX) proteins, serving as substrate recognition component of S phase kinase-associated protein 1-Cullin 1-FBX protein complexes. As a tumor suppressor, FBXW7 recognizes numerous proto-oncoproteins and promotes their ubiquitination and subsequent proteasomal degradation. FBXW7 is regulated at different levels, leading to tunable and specific control of the activity and abundance of its substrates. Therefore, genetic mutations or decreases in its expression serve an important biological role in tumor development. In-depth studies and identification of additional substrates targeted by FBXW7 have suggested a signaling network regulated by FBXW7, including its tumor-inhibitory role. The present review focused on the role of FBXW7 in tumor suppression and its application in cancer therapy. Contents 1. Introduction 2. Transcriptional and translational regulation of FBXW7 expression 3. Post-translational modifications of FBXW7 4. Genetic alterations of FBXW7 in cancers 5. Substrates and mechanisms of FBXW7 involved in tumor suppression 6. Therapeutic exploitation of FBXW7 signaling 7. Conclusions