Ohta Tomohiko, Fukuda Mamoru
Division of Breast and Endocrine Surgery, St Marianna University School of Medicine, Kawasaki 216-8511, Japan.
Oncogene. 2004 Mar 15;23(11):2079-88. doi: 10.1038/sj.onc.1207371.
The regulation of protein stability by the ubiquitin-proteasome pathway is a critical issue central to the comprehension of the molecular basis of carcinogenesis. However, ubiquitin modification of target substrates signals many cellular processes other than proteolysis that are also important for the development of cancer. It is noteworthy that many proteins studied by clinical breast cancer researchers are involved in these ubiquitin pathways. This review summarizes recent works on such proteins including cyclins, CDK inhibitors, and the SCF in cell cycle control; the breast and ovarian cancer suppressor BRCA1-BARD1; ErbB2/HER2/Neu and its ubiquitin ligase c-Cbl or CHIP; and the estrogen receptor and its downstream target Efp. Understanding these pathways may provide some hints toward developing diagnostic tools and treatments for breast cancer patients.
泛素-蛋白酶体途径对蛋白质稳定性的调控是理解癌症发生分子基础的核心关键问题。然而，靶底物的泛素修饰除了信号蛋白水解外，还标志着许多其他对癌症发展也很重要的细胞过程。值得注意的是，临床乳腺癌研究人员所研究的许多蛋白质都参与了这些泛素途径。本综述总结了近期关于此类蛋白质的研究工作，包括细胞周期调控中的细胞周期蛋白、CDK抑制剂和SCF；乳腺癌和卵巢癌抑制因子BRCA1-BARD1；ErbB2/HER2/Neu及其泛素连接酶c-Cbl或CHIP；以及雌激素受体及其下游靶点Efp。了解这些途径可能为开发乳腺癌患者的诊断工具和治疗方法提供一些线索。
