Receptor interacting protein 1 (RIP1) kinase is a critical regulator of inflammation and cell death signaling, and plays a crucial role in maintaining immune responses and proper tissue homeostasis. Mounting evidence argues for the importance of RIP1 post-translational modifications in control of its function. Ubiquitination by E3 ligases, such as inhibitors of apoptosis (IAP) proteins and LUBAC, as well as the reversal of these modifications by deubiquitinating enzymes, such as A20 and CYLD, can greatly influence RIP1 mediated signaling. In addition, cleavage by caspase-8, RIP1 autophosphorylation, and phosphorylation by a number of signaling kinases can greatly impact cellular fate. Disruption of the tightly regulated RIP1 modifications can lead to signaling disbalance in TNF and/or TLR controlled and other inflammatory pathways, and result in severe human pathologies. This review will focus on RIP1 and its many modifications with an emphasis on ubiquitination, phosphorylation, and cleavage, and their functional impact on the RIP1's role in signaling pathways.

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RIP1 翻译后修饰

受体相互作用蛋白 1 (RIP1) 激酶是炎症和细胞死亡信号传导的关键调节剂，在维持免疫反应和适当的组织稳态方面起着至关重要的作用。越来越多的证据表明 RIP1 翻译后修饰在控制其功能方面的重要性。E3 连接酶泛素化，如凋亡抑制剂 (IAP) 蛋白和 LUBAC，以及去泛素化酶如 A20 和 CYLD 逆转这些修饰，可以极大地影响 RIP1 介导的信号传导。此外，caspase-8 的切割、RIP1 自身磷酸化和许多信号激酶的磷酸化可极大地影响细胞命运。破坏严格调节的 RIP1 修饰会导致 TNF 和/或 TLR 控制的和其他炎症通路的信号失衡，并导致严重的人类病态。本综述将重点关注 RIP1 及其许多修饰，重点是泛素化、磷酸化和切割，以及它们对 RIP1 在信号通路中的作用的功能影响。