Department of Biosciences, Rice University, Houston, TX, 77005, USA.
Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, People's Republic of China.
Cell Commun Signal. 2023 Nov 28;21(1):340. doi: 10.1186/s12964-023-01239-5.
Linear ubiquitination is a distinct type of ubiquitination that involves attaching a head-to-tail polyubiquitin chain to a substrate protein. Early studies found that linear ubiquitin chains are essential for the TNFα- and IL-1-mediated NF-κB signaling pathways. However, recent studies have discovered at least sixteen linear ubiquitination substrates, which exhibit a broader activity than expected and mediate many other signaling pathways beyond NF-κB signaling. Dysregulation of linear ubiquitination in these pathways has been linked to many types of cancers, such as lymphoma, liver cancer, and breast cancer. Since the discovery of linear ubiquitin, extensive effort has been made to delineate the molecular mechanisms of how dysregulation of linear ubiquitination causes tumorigenesis and cancer development. In this review, we highlight newly discovered linear ubiquitination-mediated signaling pathways, recent advances in the role of linear ubiquitin in different types of cancers, and the development of linear ubiquitin inhibitors. Video Abstract.
线性泛素化是一种独特的泛素化类型，涉及将从头至尾的多泛素链连接到底物蛋白上。早期研究发现，线性泛素链对于 TNFα 和 IL-1 介导的 NF-κB 信号通路至关重要。然而，最近的研究发现了至少十六种线性泛素化底物，它们表现出比预期更广泛的活性，并介导许多其他信号通路，而不仅仅是 NF-κB 信号通路。这些通路中线性泛素化的失调与多种癌症有关，如淋巴瘤、肝癌和乳腺癌。自线性泛素的发现以来，人们已经做出了广泛的努力来阐明线性泛素化失调如何导致肿瘤发生和癌症发展的分子机制。在这篇综述中，我们重点介绍了新发现的线性泛素化介导的信号通路、线性泛素在不同类型癌症中的作用的最新进展，以及线性泛素抑制剂的开发。视频摘要。
