A single NFκB system for both canonical and non-canonical signaling.

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 Res

journal_title

Cell research

authors

Shih VF,Tsui R,Caldwell A,Hoffmann A

doi

10.1038/cr.2010.161

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

86-102

issue

1

eissn

1001-0602

issn

1748-7838

pii

cr2010161

journal_volume

21

pub_type

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