Ca2{+}/S100 proteins inhibit the interactions of FKBP38 with Bcl-2 and Hsp90

FKBP38 (FK506-binding protein 38), a membrane-anchored, tetratricopeptide repeat (TPR)-containing immunophilin, regulates signaling pathways such as cell survival, apoptosis, proliferation, and metastasis. However, the mechanisms that regulate the activity of FKBP38 are, at present, poorly understood. We previously reported that Ca2+/S100 proteins directly associate with the TPR-proteins, such as Hsp70/Hsp90-organizing protein (Hop), kinesin-light chain, Tom70, FKBP52, CyP40, C-terminus of Hsc70-interacting protein (CHIP) and protein phosphatase 5 (PP5), leading to the dissociation of the interactions of the TPR-proteins with their target proteins. Therefore, we have hypothesized that Ca2+/S100 proteins can interact with FKBP38 and regulate its function. In vitro binding studies demonstrated that S100A1, S100A2, S100A6, S100B, and S100P specifically interact with FKBP38 and inhibit the interaction of FKBP38 with Bcl-2 and Hsp90. Overexpression of permanently active S100P in Huh-7 cells inhibited the interaction of FKBP38 with Bcl-2, resulting in the suppression of Bcl-2 stability. The association of the S100 proteins with FKBP38 provides a Ca2+-dependent regulatory mechanism of the FKBP38 mediated signaling pathways.

Source: BJ Signal - December 3, 2013 Category: Biochemistry Authors: S Shimamoto, M Tsuchiya, F Yamaguchi, Y Kubota, H Tokumitsu, R Kobayashi Tags: BJ Signal Source Type: research