Regulation of Fibroblast Activation Protein-α Expression: Focus on Intracellular Protein Interactions

(myo)fibroblasts permanently replace normal tissues. The mechanisms of regulation and elimination of FAP-α expression in(myo)fibroblasts are unknown. According to a yeast two-hybrid screen and protein databanks search, we propose that the intracellular (co)-chaperone BAG6/BAT3 can interact with FAP-α, mediated by the BAG6/BAT3 Pro-rich domain, inducing proteosomal degradation of FAP-α protein under tissue homeostasis. In this Perspective, we discuss our findings in the context of current knowledge on the regulation of FAP-α expression and comment potential therapeutic strategies for uncontrolled fibrosis, including small molecule degraders (PROTACs)-modified FAP-α targeted inhibitors.