Wei Xi, Fried Joshua, Li Ying, Hu Linfei, Gao Ming, Zhang Sheng, Xu Bo
Department of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Department of Oncology, Southern Research Institute and Cancer Cell Biology Program, University of Alabama at Birmingham Graduate School, Birmingham, AL, 35205.
J Cancer. 2018 Sep 7;9(18):3257-3262. doi: 10.7150/jca.25930. eCollection 2018.
Understanding the functional significance of the essential elements in maintaining genomic stability provides insights into the process of tumor initiation and progression, and predicts therapeutic responses. One such element that has recently attracted significant attention is the Speckle-Type Poz Protein (SPOP), an E3 ubiquitin ligase adaptor protein. SPOP is frequently mutated or has altered expression in various cancers, including prostate, renal and endometrial. SPOP is involved in the regulation of proteasome-mediated degradation of several oncoproteins. Moreover, recent data also indicate SPOP's direct involvement in the DNA damage response. SPOP mutants induce alternations in the DNA damage repair pathway by promoting the error-prone Non-homologous end joining (NHEJ) pathway. SPOP has been linked with significant functions in cellular signaling pathways and cancer suppression. This mini-review will discuss recent findings regarding SPOP's role in genomic stability in the pathological setting.
了解维持基因组稳定性的必需元件的功能意义有助于深入了解肿瘤发生和发展过程,并预测治疗反应。最近引起广泛关注的一个这样的元件是斑点型Poz蛋白(SPOP),一种E3泛素连接酶衔接蛋白。SPOP在包括前列腺癌、肾癌和子宫内膜癌在内的各种癌症中经常发生突变或表达改变。SPOP参与蛋白酶体介导的几种癌蛋白降解的调控。此外,最近的数据还表明SPOP直接参与DNA损伤反应。SPOP突变体通过促进易出错的非同源末端连接(NHEJ)途径诱导DNA损伤修复途径的改变。SPOP与细胞信号通路和癌症抑制中的重要功能有关。本综述将讨论关于SPOP在病理环境中基因组稳定性作用的最新发现。