Abstract：
FBXW7 is one of the most well-characterized F-box proteins, serving as substrate receptor subunit of SKP1-CUL1-F-box (SCF) E3 ligase complexes. SCFFBXW7 is responsible for the degradation of various oncogenic proteins such as cyclin E, c-MYC, c-JUN, NOTCH, and MCL1. Therefore, FBXW7 functions largely as a major tumor suppressor. In keeping with this notion, FBXW7 gene mutations or downregulations have been found and reported in many types of malignant tumors, such as endometrial, colorectal, lung, and breast cancers, which facilitate the proliferation, invasion, migration, and drug resistance of cancer cells. Therefore, it is critical to review newly identified FBXW7 regulation and tumor suppressor function under physiological and pathological conditions to develop effective strategies for the treatment of FBXW7-altered cancers. Since a growing body of evidence has revealed the tumor-suppressive activity and role of FBXW7, here, we updated FBXW7 upstream and downstream signaling including FBXW7 ubiquitin substrates, the multi-level FBXW7 regulatory mechanisms, and dysregulation of FBXW7 in cancer, and discussed promising cancer therapies targeting FBXW7 regulators and downstream effectors, to provide a comprehensive picture of FBXW7 and facilitate the study in this field.
摘要：
FBXW7是特征最明确的F-box蛋白之一，充当SKP1-CUL1-F-box（SCF）E3连接酶复合物的底物受体亚基。SCFFBXW7负责降解各种致癌蛋白，如细胞周期蛋白E，c-MYC,c-JUN,NOTCH,和MCL1。因此,FBXW7主要作为主要的肿瘤抑制因子发挥作用。按照这个概念，FBXW7基因突变或下调已在许多类型的恶性肿瘤中发现并报道，如子宫内膜，结直肠,肺，和乳腺癌，这促进了扩散，入侵,迁移,和癌细胞的耐药性。因此,回顾新发现的FBXW7在生理和病理条件下的调节和肿瘤抑制功能，以开发治疗FBXW7改变的癌症的有效策略至关重要。由于越来越多的证据揭示了FBXW7的肿瘤抑制活性和作用，我们更新了FBXW7上游和下游信号，包括FBXW7泛素底物，FBXW7的多层次监管机制，和癌症中FBXW7的失调，并讨论了针对FBXW7调节因子和下游效应因子的有希望的癌症疗法，提供FBXW7的全面情况，促进该领域的研究。
