The Affiliated Hospital of Medical School, Ningbo University, Ningbo 315020, China; Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathphysiology, Medical School of Ningbo University, Ningbo 315211, China.
The Affiliated Hospital of Medical School, Ningbo University, Ningbo 315020, China; Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathphysiology, Medical School of Ningbo University, Ningbo 315211, China.
Gene. 2023 Jan 30;851:146972. doi: 10.1016/j.gene.2022.146972. Epub 2022 Oct 17.
E3 ligases are involved in various cellular biological processes, and their loss of function or improper targeting can induce multiple types of human diseases. F-box protein 7(FBXO7) is a unit in the SKP1-Cullin1-F-box (SCF) SCF E3 ligase composite, playing the role of recognizing some substrates. Additionally, FBXO7 is involved in the regulation of the proteasome complex, mitophagy, the cell cycle, cell proliferation, and germ cell differentiation. Although many articles have reviewed the pathogenesis of FBXO7, which is associated with Parkinson disease-15 (PARKIN15), a summary of the role of FBXO7 as an E3 ligase and its SCF-independent function is incomplete, as well as an overview of FBXO7 in cancer. Therefore, we summarized FBXO7-related substrates and the roles of FBXO7 in human cancers. In addition, based on previous studies, we supplemented the newly discovered FBXO7 mutations in PARKIN15 patients and some potential pathogenic mechanisms that may lead to PARKIN15. A profound exploration of the general pathophysiological mechanisms of this protein could provide potential evidence for the targeted treatment of PARKIN15 and malignant tumors.
E3 连接酶参与多种细胞生物学过程，其功能丧失或靶向不当可诱发多种人类疾病。F-box 蛋白 7（FBXO7）是 SKP1-Cullin1-F-box（SCF）SCF E3 连接酶复合物中的一个单位，起到识别某些底物的作用。此外，FBXO7 还参与蛋白酶体复合物、线粒体自噬、细胞周期、细胞增殖和生殖细胞分化的调节。尽管许多文章已经综述了与帕金森病 15 型（PARKIN15）相关的 FBXO7 的发病机制，但作为 E3 连接酶及其 SCF 非依赖性功能的 FBXO7 的作用综述并不完整，也没有 FBXO7 在癌症中的概述。因此，我们总结了 FBXO7 相关的底物以及 FBXO7 在人类癌症中的作用。此外，基于先前的研究，我们补充了 PARKIN15 患者中新发现的 FBXO7 突变以及一些可能导致 PARKIN15 的潜在致病机制。深入探索该蛋白的一般病理生理机制，可为靶向治疗 PARKIN15 和恶性肿瘤提供潜在证据。
