Contribution of Mass Spectrometry-Based Proteomics to the Understanding of TNF‑α Signaling

NF-κB is a family of ubiquitous dimeric transcription factors that play a role in a myriad of cellular processes, ranging from differentiation to stress response and immunity. In inflammation, activation of NF-κB is mediated by pro-inflammatory cytokines, in particular the prototypic cytokines IL-1β and TNF-α, which trigger the activation of complex signaling cascades. In spite of decades of research, the system level understanding of TNF-α signaling is still incomplete. This is partially due to the limited knowledge at the proteome level. The objective of this review is to summarize and critically evaluate the current status of the proteomic research on TNF-α signaling. We will discuss the merits and flaws of the existing studies as well as the insights that they have generated into the proteomic landscape and architecture connected to this signaling pathway. Besides delineating past and current trends in TNF-α proteomic research, we will identify research directions and new methodologies that can further contribute to characterize the TNF-α associated proteome in space and time.