FKBP38-Bcl-2 interaction: a novel link to chemoresistance

FKBP38, a noncanonical member of the immunosuppressive drug FK506 binding protein (FKBP) family members, possesses an inducible rotamase. FKBP38 interacts with several proteins and regulates multiple signaling pathways such as cell survival, apoptosis, proliferation, and metastasis. Deregulation of apoptosis is associated with chemoresistance and tumor relapse. The antiapoptotic protein Bcl-2 is a key player for increasing the apoptotic threshold in response to various cytotoxic drugs. The molecular interaction of Bcl-2 with FKBP38 potentiates the biological function of Bcl-2 and contributes to tumorigenesis and chemoresistance. Here, we discuss recent advances in the role of FKBP38 in connection with Bcl-2 and its possible link to chemotherapeutic resistance.

► FKBP38 interacts with Bcl-2 and enhances the stability of Bcl-2.
► FKBP38 enhances the anti-apoptotic ability of Bcl-2.
► Increased level of FKBP38 contributes to Bcl-2-mediated chemoresistance.