Papers

Peer-reviewed
Oct, 2008

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

The Journal of Biological Chemistry
  • Seiko Shimamoto
  • ,
  • Maki Takata
  • ,
  • Masaaki Tokuda
  • ,
  • Fumikazu Oohira
  • ,
  • Hiroshi Tokumitsu
  • ,
  • Ryoji Kobayashi

Volume
283
Number
42
First page
28246
Last page
28258
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.1074/jbc.M801473200
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

S100A2 and S100A6 interact with several target proteins in a Ca2+-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 andregulates 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.

Link information
DOI
https://doi.org/10.1074/jbc.M801473200
CiNii Articles
http://ci.nii.ac.jp/naid/80019829218
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/18669640
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000259969300026&DestApp=WOS_CPL
ID information
  • DOI : 10.1074/jbc.M801473200
  • ISSN : 0021-9258
  • CiNii Articles ID : 80019829218
  • Pubmed ID : 18669640
  • Web of Science ID : WOS:000259969300026

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