Figure 2.

Difference between SHARPIN presence and absence in regulating the NF-κB signaling pathway and integrin activation. (A) Normal SHARPIN expression. SHARPIN is found to be expression in platelets, can respond associated with aIIbβ3, inhibit aIIbβ3 activation with aIIb, and can also participate in the formation of LUBAC, thereby promoting Met1 ubiquitination. Stimulation of platelets through receptors for TNFα, LPS, 1l-1β or CD40 activates LUBAC to add Met1 linear ubiquitin chains (yellow circles) to NEMO, provoking transautophosphorylation of IKKβ and phosphorylation of IκBα. In nucleated cells, Lys-48-ubiquitination (yellow circles) results in degradation of IκBα, which frees NF-κB for nuclear translocation. (B) Effects of SHARPIN knockdown. Reduction of SHARPIN levels associated with αIIb prime αIIbβ3 activation and fibrinogen binding. Reduction in SHARPIN levels also destabilize LUBAC. Only a selected number of factors of the TNFR1-associated signaling complex are depicted.