Yang Yibin, Staudt Louis M
Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Immunol Rev. 2015 Jan;263(1):240-56. doi: 10.1111/imr.12247.
Human lymphoid malignancies inherit gene expression networks from their normal B-cell counterpart and co-opt them for their own oncogenic purpose, which is usually governed by transcription factors and signaling pathways. These transcription factors and signaling pathways are precisely regulated at multiple steps, including ubiquitin modification. Protein ubiqutination plays a role in almost all cellular events and in many human diseases. In the past few years, multiple studies have expanded the role of ubiquitination in the genesis of diverse lymphoid malignancies. Here, we discuss our current understanding of both proteolytic and non-proteolytic functions of the protein ubiquitination system and describe how it is involved in the pathogenesis of human lymphoid cancers. Lymphoid-restricted ubiquitination mechanisms, including ubiquitin E3 ligases and deubiquitinating enzymes, provide great opportunities for the development of targeted therapies for lymphoid cancers.
人类淋巴恶性肿瘤从其正常B细胞对应物继承基因表达网络,并将其用于自身的致癌目的,这通常受转录因子和信号通路调控。这些转录因子和信号通路在多个步骤受到精确调控,包括泛素修饰。蛋白质泛素化几乎在所有细胞事件以及许多人类疾病中都发挥作用。在过去几年中,多项研究扩展了泛素化在多种淋巴恶性肿瘤发生中的作用。在此,我们讨论对蛋白质泛素化系统的蛋白水解和非蛋白水解功能的当前理解,并描述其如何参与人类淋巴癌的发病机制。淋巴特异性泛素化机制,包括泛素E3连接酶和去泛素化酶,为淋巴癌靶向治疗的发展提供了巨大机遇。