Xia Qin, Li Yang, Han Da, Dong Lei
School of Life Science, Beijing Institute of Technology, Beijing, China.
Cancer Gene Ther. 2021 Jun;28(6):551-565. doi: 10.1038/s41417-020-00255-8. Epub 2020 Nov 17.
Overexpression of HECT-type E3 ubiquitin ligase SMURF1 is correlated with poor prognosis in patients with various cancers, such as glioblastoma, colon cancer, and clear cell renal cell carcinoma. SMURF1 acts as a tumor promoter by ubiquitination modification and/or degradation of tumor-suppressing proteins. Combined treatment of Smurf1 knockdown with rapamycin showed collaborative antitumor effects in mice. This review described the role of HECT, WW, and C2 domains in regulating SMURF1 substrate selection. We summarized up to date SMURF1 substrates regulating different type cell signaling, thus, accelerating tumor progression, invasion, and metastasis. Furthermore, the downregulation of SMURF1 expression, inhibition of its E3 activity and regulation of its specificity to substrates prevent tumor progression. The potential application of SMURF1 regulators, specifically, wisely choose certain drugs by blocking SMURF1 selectivity in tumor suppressors, to develop novel anticancer treatments.
HECT型E3泛素连接酶SMURF1的过表达与多种癌症患者的不良预后相关，如胶质母细胞瘤、结肠癌和透明细胞肾细胞癌。SMURF1通过对肿瘤抑制蛋白进行泛素化修饰和/或降解而发挥肿瘤促进作用。在小鼠中，Smurf1基因敲低与雷帕霉素联合治疗显示出协同抗肿瘤作用。这篇综述描述了HECT、WW和C2结构域在调节SMURF1底物选择中的作用。我们总结了迄今为止调节不同类型细胞信号传导从而加速肿瘤进展、侵袭和转移的SMURF1底物。此外，SMURF1表达的下调、其E3活性的抑制以及对其底物特异性的调节可阻止肿瘤进展。SMURF1调节剂的潜在应用，具体而言，通过阻断SMURF1对肿瘤抑制因子的选择性来明智地选择某些药物，以开发新的抗癌治疗方法。
