Zhu Qiaojuan, Hu Linjun, Guo Yang, Xiao Zunqiang, Xu Qiuran, Tong Xiangmin
The Second Clinical Medical Department, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310014, P.R. China.
Medical Department, Qingdao University, Qingdao, Shandong 266071, P.R. China.
Oncol Lett. 2020 Mar;19(3):1657-1664. doi: 10.3892/ol.2020.11264. Epub 2020 Jan 8.
F-box and WD repeat domain-containing protein 7 (FBW7), also known as FBXW7, AGO or hCDC4, is an F-box protein with seven tandem WD40 repeats. FBW7 is a key substrate recognition subunit of the Skp1-Cul1-F-box-protein E3 ubiquitin ligase. FBW7 targets for ubiquitination and destruction of numerous crucial transcription factors and protooncogenes, including cyclin E, c-Myc, c-Jun, Notch and MCL-1. FBW7 is a well-characterized tumor suppressor, and its gene is frequently mutated or deleted in various types of human cancer, including colorectal cancer, gastric cancer, ovarian cancer and different types of leukemia. Accumulating evidence indicates that the aberrant expression of FBW7 is involved in the development of hematological tumors, including T cell acute lymphoblastic leukemia, adult T cell leukemia/lymphoma, chronic lymphocytic leukemia and multiple myeloma. The present review will describe the latest findings on the role of FBW7 in hematological tumors, in order to identify a novel target for future therapies.
含F盒和WD重复结构域蛋白7（FBW7），也称为FBXW7、AGO或hCDC4，是一种具有七个串联WD40重复序列的F盒蛋白。FBW7是Skp1-Cul1-F盒蛋白E3泛素连接酶的关键底物识别亚基。FBW7靶向多种关键转录因子和原癌基因进行泛素化和降解，包括细胞周期蛋白E、c-Myc、c-Jun、Notch和MCL-1。FBW7是一种特征明确的肿瘤抑制因子，其基因在包括结直肠癌、胃癌、卵巢癌和不同类型白血病在内的多种人类癌症中经常发生突变或缺失。越来越多的证据表明，FBW7的异常表达与血液系统肿瘤的发生发展有关，包括T细胞急性淋巴细胞白血病、成人T细胞白血病/淋巴瘤、慢性淋巴细胞白血病和多发性骨髓瘤。本综述将描述FBW7在血液系统肿瘤中作用的最新发现，以便为未来治疗确定新的靶点。
