Department of Molecular and Human Genetics, Institute of Science, Banaras Hindu University, Varanasi, India.
FEBS J. 2022 Feb;289(4):937-954. doi: 10.1111/febs.15792. Epub 2021 Mar 16.
Notch signaling is an evolutionarily conserved pathway that is widely used for multiple cellular events during development. Activation of the Notch pathway occurs when the ligand from a neighboring cell binds to the Notch receptor and induces cleavage of the intracellular domain of Notch, which further translocates into the nucleus to activate its downstream genes. The involvement of the Notch pathway in diverse biological events is possible due to the complexity in its regulation. In order to maintain tight spatiotemporal regulation, the Notch receptor, as well as its ligand, undergoes a series of physical and biochemical modifications that, in turn, helps in proper maintenance and fine-tuning of the signaling outcome. Ubiquitination is the post-translational addition of a ubiquitin molecule to a substrate protein, and the process is regulated by E3 ubiquitin ligases. The present review describes the involvement of different E3 ubiquitin ligases that play an important role in the regulation and maintenance of proper Notch signaling and how perturbation in ubiquitination results in abnormal Notch signaling leading to a number of human diseases.
Notch 信号通路是一种进化上保守的途径，在发育过程中广泛用于多种细胞事件。当相邻细胞的配体与 Notch 受体结合并诱导 Notch 胞内结构域的切割时，Notch 通路被激活，进一步转位到细胞核中以激活其下游基因。Notch 通路参与多种生物事件的可能性归因于其调节的复杂性。为了维持严格的时空调节，Notch 受体及其配体经历了一系列的物理和生化修饰，这反过来有助于适当维持和精细调节信号转导的结果。泛素化是将一个泛素分子添加到底物蛋白上的翻译后修饰过程，该过程受到 E3 泛素连接酶的调节。本综述描述了不同的 E3 泛素连接酶在 Notch 信号通路的调节和维持中的重要作用，以及泛素化的干扰如何导致异常的 Notch 信号通路，从而导致许多人类疾病。
