Reduced S-nitrosylation of TGFβ1 elevates its binding affinity towards the receptor and promotes fibrogenic signaling in the breast.

Transforming Growth Factor β (TGFβ) is a widely studied cytokine associated with tumors. Because of its pleiotropic functions and dichotomous roles in tumorigenesis, the development of therapeutics targeted to TGFβ for cancer treatment has been challenging. In the present study, we report that TGFβ is indeed S-nitrosylated at specific sites for repressing its functions, whereas it is denitrosylated to derepress its activity. Such covalent modification-based regulation of TGFβ activity could potentially be utilized to design a new type of inhibitor or activator of the protein.