Biomedical Pioneering Innovation Center (BIOPIC), Beijing Advanced Innovation Center for Genomics, Peking-Tsinghua Center for Life Sciences, Peking University Genome Editing Research Center, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.
Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Biomed Pharmacother. 2023 Sep;165:115190. doi: 10.1016/j.biopha.2023.115190. Epub 2023 Jul 26.
The STUB1 gene (STIP1 homology and U-box-containing protein 1), located at 16q13.3, encodes the CHIP (carboxyl terminus of Hsc70-interacting protein), an essential E3 ligase involved in protein quality control. CHIP comprises three domains: an N-terminal tetratricopeptide repeat (TPR) domain, a middle coiled-coil domain, and a C-terminal U-box domain. It functions as a co-chaperone for heat shock protein (HSP) via the TPR domain and as an E3 ligase, ubiquitinating substrates through its U-box domain. Numerous studies suggest that STUB1 plays a crucial role in various physiological process, such as aging, autophagy, and bone remodeling. Moreover, emerging evidence has shown that STUB1 can degrade oncoproteins to exert tumor-suppressive functions, and it has recently emerged as a novel player in tumor immunity. This review provides a comprehensive overview of STUB1's role in cancer, including its clinical significance, impact on tumor progression, dual roles, tumor stem cell-like properties, angiogenesis, drug resistance, and DNA repair. In addition, we explore STUB1's functions in immune cell differentiation and maturation, inflammation, autoimmunity, antiviral immune response, and tumor immunity. Collectively, STUB1 represents a promising and valuable therapeutic target in cancer and immunology.
STUB1 基因（STIP1 同源和 U -box 蛋白 1）位于 16q13.3，编码 CHIP（Hsc70 相互作用蛋白的羧基末端），这是一种参与蛋白质质量控制的必需 E3 连接酶。CHIP 包含三个结构域：N 端四肽重复（TPR）结构域、中间卷曲螺旋结构域和 C 端 U 盒结构域。它通过 TPR 结构域作为热休克蛋白（HSP）的共伴侣，通过其 U 盒结构域作为 E3 连接酶，泛素化底物。许多研究表明，STUB1 在各种生理过程中发挥着关键作用，如衰老、自噬和骨重塑。此外，新出现的证据表明，STUB1 可以降解癌蛋白以发挥肿瘤抑制功能，它最近作为肿瘤免疫的新参与者出现。这篇综述全面概述了 STUB1 在癌症中的作用，包括其临床意义、对肿瘤进展的影响、双重作用、肿瘤干细胞样特性、血管生成、耐药性和 DNA 修复。此外，我们还探讨了 STUB1 在免疫细胞分化和成熟、炎症、自身免疫、抗病毒免疫反应和肿瘤免疫中的功能。总之，STUB1 代表了癌症和免疫学中一个有前途和有价值的治疗靶点。
