Abstract:
:Two distinct nuclear factor κB (NFκB) signaling pathways have been described; the canonical pathway that mediates inflammatory responses, and the non-canonical pathway that is involved in immune cell differentiation and maturation and secondary lymphoid organogenesis. The former is dependent on the IκB kinase adaptor molecule NEMO, the latter is independent of it. Here, we review the molecular mechanisms of regulation in each signaling axis and attempt to relate the apparent regulatory logic to the physiological function. Further, we review the recent evidence for extensive cross-regulation between these two signaling axes and summarize them in a wiring diagram. These observations suggest that NEMO-dependent and -independent signaling should be viewed within the context of a single NFκB signaling system, which mediates signaling from both inflammatory and organogenic stimuli in an integrated manner. As in other regulatory biological systems, a systems approach including mathematical models that include quantitative and kinetic information will be necessary to characterize the network properties that mediate physiological function, and that may break down to cause or contribute to pathology.
journal_name
Cell Resjournal_title
Cell researchauthors
Shih VF,Tsui R,Caldwell A,Hoffmann Adoi
10.1038/cr.2010.161subject
Has Abstractpub_date
2011-01-01 00:00:00pages
86-102issue
1eissn
1001-0602issn
1748-7838pii
cr2010161journal_volume
21pub_type
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