Over the last two decades the mechanisms that underpin cell survival and cell death have been intensively studied. One molecule in particular, Receptor Interacting Protein Kinase 1 (RIPK1), has gained interest due to the ability to function upstream of both NF-κB signaling and caspase-dependent and –independent cell death. RIPK1 is critical in determining cell fate downstream of cytokine signaling receptors such as the Tumour Necrosis Factor Receptor Super Family (TNFRSF) and the innate immune Toll-like receptors. Various studies have attempted to untangle how ubiquitination of RIPK1 dictates signaling outcomes; however, due to the complex nature of ubiquitin signaling it has been difficult to prove that ubiquitination of RIPK1 does in fact influence signaling outcomes. Therefore, we ask the question: What do we really know about RIPK1 ubiquitination, and, to what extent can we conclude that ubiquitination of RIPK1 impacts RIPK1-mediated signaling events?

在过去的二十年里，人们对支持细胞存活和细胞死亡的机制进行了深入研究。特别是一种分子，受体相互作用蛋白激酶 1 (RIPK1)，由于能够在 NF-κB 信号传导和半胱天冬酶依赖性和非依赖性细胞死亡的上游起作用的能力而引起了人们的兴趣。RIPK1 对于确定细胞因子信号受体下游的细胞命运至关重要，例如肿瘤坏死因子受体超家族 (TNFRSF) 和先天免疫 Toll 样受体。各种研究试图解开 RIPK1 泛素化如何决定信号转导结果；然而，由于泛素信号传导的复杂性，很难证明 RIPK1 的泛素化确实会影响信号传导结果。因此，我们提出以下问题：