Figure 1.

Defective CFTR-induced perturbation of the post-translational network in CF epithelial cells. Defective CFTR leads to increased levels of reactive oxygen species (ROS) that increase the levels of the SUMO E3-ligase PIASy, causing TG2 SUMOylation, that, in turn, inhibits TG2 ubiquitination, and avoids its proteosomal degradation, thus sustaining increased TG2 protein levels. Sustained TG2 activation mediates crosslinking of PPARγ and IκBα, which undergo ubiquitination and proteasome degradation. This inhibits nuclear translocation of PPARγ and favors nuclear translocation of NF-κB, stimulating inflammation.