The small molecule that packs a punch: ubiquitin-mediated regulation of RIPK1/FADD/caspase-8 complexes

摘要

>The mechanisms that underpin the production of small molecules and cytokines that lead to inflammation or programmed cell death are intricately intertwined. So much so that some of the proteins that contribute to the transcriptional up regulation of cytokines can switch their role in the right circumstances to generate cell death-inducing complexes. This entwinement is reflected in the fact that inflammation helps an organism fight pathogens and that therefore pathogens are under an evolutionary pressure to interfere with this process. Cell death is therefore a defensive measure that may serve to deny pathogens a host cell, expose pathogens to the immune system and also provide additional inflammatory information to the host. Clearly such a system must be tightly regulated and ubiquitylation is a post-translational protein modification that is at the heart of this regulation. In this review, we discuss the regulatory ubiquitin events that dictate the formation and activation of death-inducing complexes containing RIPK1/FADD/caspase-8, and examine how these events collectively determine cell fate.