Centre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, London WC1E 6BT, UK.
Centre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, London WC1E 6BT, UK.
Trends Cell Biol. 2016 Jun;26(6):445-461. doi: 10.1016/j.tcb.2016.01.006. Epub 2016 Feb 11.
The kinase RIPK1 is an essential signaling node in various innate immune signaling pathways being most extensively studied in the TNFR1 signaling pathway. TNF signaling can result in different biological outcomes including gene activation and cell death induction in the form of apoptosis or necroptosis. RIPK1 is believed to be crucial for regulating the balance between these opposing outcomes. It is therefore not surprising that RIPK1 is highly regulated, most notably by phosphorylation, ubiquitination, and their respective reversals. In this review, we discuss the biological functions of RIPK1 within the context of TNFR1 signaling. Finally, we discuss recent advances in the knowledge on three ubiquitin E3 ligases that exert regulatory functions on RIPK1 signaling: cIAP1, cIAP2, and LUBAC.
激酶 RIPK1 是各种先天免疫信号通路中的一个重要信号节点，在 TNFR1 信号通路中研究得最为广泛。TNF 信号可以导致不同的生物学结果，包括基因激活和以细胞凋亡或坏死性凋亡的形式诱导细胞死亡。RIPK1 被认为对于调节这些相反结果之间的平衡至关重要。因此，RIPK1 受到高度调节并不奇怪，尤其是通过磷酸化、泛素化及其各自的逆转。在这篇综述中，我们将讨论 RIPK1 在 TNFR1 信号中的生物学功能。最后，我们讨论了关于三种对 RIPK1 信号具有调节功能的泛素 E3 连接酶的最新进展：cIAP1、cIAP2 和 LUBAC。
