Ca2+/S100 proteins inhibit the interaction of FKBP38 with Bcl-2 and Hsp90

Seiko Shimamoto, Mitsumasa Tsuchiya, Fuminori Yamaguchi, Yasuo Kubota, Hiroshi Tokumitsu, Ryoji Kobayashi

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

FKBP38 (FK506-binding protein 38), amembrane-anchored TPR (tetratricopeptide repeat)-containing immunophilin, regulates signalling pathways such as cell survival, apoptosis, proliferation andmetastasis.However, themechanisms 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 Hop [Hsp70 (heat-shock protein of 70 kDa)/Hsp90-organizing protein], kinesin-light chain, Tom70 (translocase of outer mitochondrial membrane 70), FKBP52, CyP40 (cyclophilin 40), CHIP (C-terminus of Hsc70-interacting protein) and PP5 (protein phosphatase 5), 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 signalling pathways.

Original languageEnglish
Pages (from-to)141-152
Number of pages12
JournalBiochemical Journal
Volume458
Issue number1
DOIs
Publication statusPublished - Jan 15 2014
Externally publishedYes

Keywords

  • Bcl-2
  • Calcium-binding protein
  • Calmodulin
  • FK506-binding protein 38 (FKBP38)
  • Heat-shock protein of 90 kDa (Hsp90)
  • S100 protein
  • Tetratricopeptide repeat

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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