Centre Pluridisciplinaire d'Oncologie, BH06, University Hospital of Lausanne, Lausanne, Switzerland.
Mol Biol Rep. 2013 Feb;40(2):2019-34. doi: 10.1007/s11033-012-2261-0. Epub 2012 Nov 28.
Breast cancer is the most common malignancy in women and a significant cause of morbidity and mortality. Sub-types of breast cancer defined by the expression of steroid hormones and Her2/Neu oncogene have distinct prognosis and undergo different therapies. Besides differing in their phenotype, sub-types of breast cancer display various molecular lesions that participate in their pathogenesis. BRCA1 is one of the common hereditary cancer predisposition genes and encodes for an ubiquitin ligase. Ubiquitin ligases or E3 enzymes participate together with ubiquitin activating enzyme and ubiquitin conjugating enzymes in the attachment of ubiquitin (ubiquitination) in target proteins. Ubiquitination is a post-translational modification regulating multiple cell functions. It also plays important roles in carcinogenesis in general and in breast carcinogenesis in particular. Ubiquitin conjugating enzymes are a central component of the ubiquitination machinery and are often perturbed in breast cancer. This paper will discuss ubiquitin and ubiquitin-like proteins conjugating enzymes participating in breast cancer pathogenesis, their relationships with other proteins of the ubiquitination machinery and their role in phenotype of breast cancer sub-types.
乳腺癌是女性最常见的恶性肿瘤,也是发病率和死亡率的重要原因。根据类固醇激素和 Her2/Neu 癌基因的表达来定义的乳腺癌亚型具有不同的预后,并接受不同的治疗。除了表型不同外,乳腺癌亚型还表现出参与其发病机制的各种分子病变。BRCA1 是常见的遗传性癌症易感性基因之一,编码一种泛素连接酶。泛素连接酶或 E3 酶与泛素激活酶和泛素缀合酶一起参与靶蛋白中泛素(泛素化)的附着。泛素化是一种调节多种细胞功能的翻译后修饰。它在一般的致癌作用中以及在乳腺癌的致癌作用中也起着重要作用。泛素缀合酶是泛素化机制的核心组成部分,在乳腺癌中经常受到干扰。本文将讨论参与乳腺癌发病机制的泛素和泛素样蛋白缀合酶、它们与泛素化机制中其他蛋白质的关系以及它们在乳腺癌亚型表型中的作用。