Defects in ubiquitin E3 ligases are implicated in the pathogenesis of several human diseases, including cancer, because of their central role in the control of diverse signaling pathways. RING E3 ligases promote the ubiquitination of proteins that are essential to a variety of cellular events. Identification of which ubiquitin ligases specifically affect distinct cellular processes is essential to the development of targeted therapeutics for these diseases. Here we discuss two novel RING E3 ligases, BCA2 and RNF11, that are closely linked to human breast cancer. BCA2 E3 ligase is coregulated with estrogen receptor and plays a role in the regulation of epidermal growth factor receptor (EGF-R) trafficking. RNF11 is a small RING E3 ligase that affects transforming growth factorbeta and EGF-R signaling and is overexpressed in invasive breast cancers. These two proteins demonstrate the complexity of RING E3 ligase interactions in breast cancer and are potential targets for therapeutic interventions.

译文

泛素E3连接酶的缺陷与多种人类疾病(包括癌症)的发病机制有关,因为它们在控制多种信号通路中起着核心作用。 RING E3连接酶可促进多种细胞事件必不可少的蛋白质的泛素化。鉴定哪些泛素连接酶特异性地影响不同的细胞过程,对于开发针对这些疾病的靶向疗法至关重要。在这里,我们讨论两种新型的RING E3连接酶BCA2和RNF11,它们与人乳腺癌密切相关。 BCA2 E3连接酶与雌激素受体共调节,并在表皮生长因子受体(EGF-R)转运的调节中发挥作用。 RNF11是一个小的RING E3连接酶,可影响转化生长因子β和EGF-R信号传导,并在浸润性乳腺癌中过表达。这两种蛋白证明了RING E3连接酶相互作用在乳腺癌中的复杂性,是治疗干预的潜在靶标。

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