Wiring diagrams of the NFKB signaling system to chart crosstalk between canonical and non-canonical signaling pathways

Wiring diagrams of the NFκB signaling system to chart crosstalk between canonical and non-canonical signaling pathways. (A) Non-canonical control of RelA:p50. RelA:p50 is inhibited by not only IκBα, -β, -ɛ, but also IκBδ. Whereas inflammatory canonical signals lead to degradation of IκBα, -β, -ɛ, developmental signals engage the non-canonical pathway to disrupt IκBδ activity; however, both result in the nuclear translocation of RelA:p50. Interestingly, prior canonical signaling history results in an enhancement of the non-canonical-RelA:p50 axis, due to inducible expression of p100. (B) Canonical control of RelB:p52 activation. Expression of p100 and RelB are dependent on RelA:p50 activity and therefore canonical signals. The amount of basal RelB expression, controlled by constitutive canonical pathway activity, rather than the inducible p100 expression, is the main determinant of the strength of non-canonical signaling.

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A single NFκB system for both canonical and non-canonical signaling. (2011) Vincent Feng-Sheng Shih, et al. Cell Res. 2011 Jan;21(1):86-102. Figure: F7. Homo sapiens

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