Unknown

Dataset Information

0

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


ABSTRACT: 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 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.

SUBMITTER: Shimamoto S 

PROVIDER: S-EPMC2661394 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Shimamoto Seiko S   Takata Maki M   Tokuda Masaaki M   Oohira Fumikazu F   Tokumitsu Hiroshi H   Kobayashi Ryoji R  

The Journal of biological chemistry 20080731 42


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 and regulates Hop-Hsp70 and Hop-Hsp90 complex formation. We have found that S100A2 and S100A6 bind to the TPR domain of  ...[more]

Similar Datasets

| S-EPMC2757238 | biostudies-literature
| S-EPMC3314626 | biostudies-literature
| S-EPMC2939883 | biostudies-literature
| S-EPMC4714923 | biostudies-literature
| S-EPMC3285342 | biostudies-literature
| S-EPMC6759711 | biostudies-literature
| S-EPMC5391737 | biostudies-literature
| S-EPMC1679764 | biostudies-literature
| S-EPMC7279152 | biostudies-literature
| S-EPMC2786975 | biostudies-literature