fig1

Figure 1. MUC1 evolved to protect epithelia from the loss of homeostasis. MUC1 encodes a single polypeptide that undergoes autocleavage into N-terminal (MUC1-N) and C-terminal (MUC1-C) subunits. MUC1-N and MUC1-C form a stable non-covalent complex mediated by a leucine zipper-like structure^[12]. The MUC1-N/MUC1-C complex is positioned at the apical borders of polarized epithelial cells. In response to the loss of homeostasis associated with pathogenic infections, damage, and other forms of stress, entropic forces in the glycocalyx promote disruption of the MUC1-N/MUC1-C complex with shedding of MUC1-N into the protective mucous barrier. In turn, activation of MUC1-C induces inflammatory, proliferative, and remodeling signaling pathways associated with wound repair^[6,13]. Figure modified from Kufe^[5,6]. MUC1: The mucin 1 gene.