A Protein Turnover Signaling Motif Controls the Stimulus-Sensitivity of Stress Response Pathways
Figure 8
A paired positive (+) and negative (−) flux motif controls stimulus-sensitivity in the p53 and NFkB stress response pathways.
(A) For p53, the (+) flux is formed by the synthesis and degradation of p53 itself. The (−) flux is formed by synthesis and degradation of Mdm2. Together these fluxes control the sensitivity of p53 to IR-stimulation, which acts by inducing the synthesis of p53 and the degradation of Mdm2. (B) For NFkB, the (+) flux is formed by association and dissociation of NFkB from its negative regulator, IκB. The (−) flux is formed by synthesis and degradation of IκB. These fluxes control the sensitivity of NFkB to TNF-stimulation, which induces the dissociation of NFκB from IκB, and UV-stimulation, which inhibits the synthesis of IκB.