Interactions of S100A2 and S100A6 with the tetratricopeptide repeat proteins, Hsp90/Hsp70-organizing protein and kinesin light chain

Seiko Shimamoto, Maki Takata, Masaaki Tokuda, Fumikazu Oohira, Hiroshi Tokumitsu, Ryoji Kobayashi

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

S100A2 and S100A6 interact with several target proteins in a Ca 2+-regulated manner. However, the exact intracellular roles of the S100 proteins are unclear. In this study we identified Hsp70/Hsp90-organizing protein (Hop) and kinesin light chain (KLC) as novel targets of S100A2 and S100A6. Hop directly associates with Hsp70 and Hsp90 through the tetratricopeptide (TPR) domains and regulates Hop-Hsp70 and Hop-Hsp90 complex formation. We have found that S100A2 and S100A6 bind to the TPR domain of Hop, resulting in inhibition of the Hop-Hsp70 and Hop-Hsp90 interactions in vitro. Although endogenous Hsp70 and Hsp90 interact with Hop in resting Cos-7 cells, but not with S100A6, stimulation of these cells with ionomycin caused a Hop-S100A6 interaction, resulting in the dissociation of Hsp70 and Hsp90 from Hop. Similarly, glutathione S-transferase pulldown and co-immunoprecipitation experiments revealed that S100A6 binds to the TPR domain of KLC, resulting in inhibition of the KLC-c-Jun N-terminal kinase (JNK)-interacting protein 1 (JIP-1) interaction in vitro. The transiently expressed JIP-1 interacts with KLC in resting Cos-7 cells but not with S100A6. Stimulation of these cells with ionomycin also caused a KLC-S100A6 interaction, resulting in dissociation of JIP-1 from KLC. These results strongly suggest that the S100 proteins modulate Hsp70-Hop-Hsp90 multichaperone complex formation and KLC-cargo interaction via Ca2+-dependent S100 protein-TPR protein complex formation in vivo as well as in vitro. Moreover, we have shown that S100A2 and S100A6 interact with another TPR protein Tom70 and regulate the Tom70-ligand interaction in vitro. Thus, our findings suggest a new intracellular Ca2+-signaling pathway via S100 proteins-TPR motif interactions.

Original languageEnglish
Pages (from-to)28246-28258
Number of pages13
JournalJournal of Biological Chemistry
Volume283
Issue number42
DOIs
Publication statusPublished - Oct 17 2008
Externally publishedYes

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Kinesin
Proteins
S100 Proteins
Light
Ionomycin
kinesin light-chain proteins
Amino Acid Motifs
JNK Mitogen-Activated Protein Kinases
Glutathione Transferase
Immunoprecipitation
Ligands
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Interactions of S100A2 and S100A6 with the tetratricopeptide repeat proteins, Hsp90/Hsp70-organizing protein and kinesin light chain. / Shimamoto, Seiko; Takata, Maki; Tokuda, Masaaki; Oohira, Fumikazu; Tokumitsu, Hiroshi; Kobayashi, Ryoji.

In: Journal of Biological Chemistry, Vol. 283, No. 42, 17.10.2008, p. 28246-28258.

Research output: Contribution to journalArticle

Shimamoto, Seiko ; Takata, Maki ; Tokuda, Masaaki ; Oohira, Fumikazu ; Tokumitsu, Hiroshi ; Kobayashi, Ryoji. / Interactions of S100A2 and S100A6 with the tetratricopeptide repeat proteins, Hsp90/Hsp70-organizing protein and kinesin light chain. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 42. pp. 28246-28258.
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AU - Tokumitsu, Hiroshi

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