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.