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Cleavage of HSP90β induced by histone deacetylase inhibitor and proteasome inhibitor modulates cell growth and apoptosis

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Cell Stress and Chaperones Aims and scope

Abstract

HSP90, one of the molecular chaperones, contributes to protein stability in most living organisms. Previously, we found cleavage of HSP90 by caspase 10 in response to treatment with histone deacetylase inhibitor or proteasome inhibitor in leukemic cell lines. In this study, we investigated this phenomenon in various cell lines and found that HSP90 was cleaved by treatment with SAHA or MG132 in 6 out of 16 solid tumor cell lines. To further investigate the effects of HSP90 cleavage on cells, we introduced mutations to the potential cleavage sites of HSP90β and found that the 294th aspartic acid residue of the protein was mainly cleaved. In the K562 and Mia-PaCa-2 cell lines expressing HSP90β D294A, the cleavage of HSP90 by the treatment with SAHA or MG132 was reduced compared with the K562 and Mia-PaCa-2 cell lines expressing HSP90β WT. Accordingly, cell growth and survival were enhanced by HSP90β D294A expression. Therefore, we suggest that HSP90 cleavage widely occurs in several cell lines, and cleavage of HSP90 may have a potential for one of the mechanisms involved in the anti-tumor effects of known drugs and novel anti-tumor drug candidates.

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Acknowledgments

We would like to thank Professor Kyu Lim at Chungnam National University for kindly providing the pancreatic cancer cell line PANC02.

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Funding

This research was supported by a grant (2018R1A2B6002504) from the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT and by the Basic Science Research Program (2019R1A6A3A01096936) through the NRF funded by the Ministry of Education in the Republic of Korea.

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Authors and Affiliations

  1. Biotechnology Research Institute, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea

    Sangkyu Park, Jeong-A Park & Younghee Lee

  2. Department of Biochemistry, College of Natural Sciences, Chungbuk National University, 1 Chungdae-Ro, Seowon-Gu, Cheongju, Chungbuk, 28644, Republic of Korea

    Jae-Hyung Jeon, Jun-Kyu Choi & Younghee Lee

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  1. Sangkyu Park
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  2. Jae-Hyung Jeon
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Sangkyu Park and Younghee Lee conceived the study and wrote the manuscript. Sangkyu Park, Jae-Hyung Jeon, Jeong-A Park, and Jun-Kyu Choi performed the experiments. Sangkyu Park, Jae-Hyung Jeon, and Younghee Lee analyzed the data and prepared figures. All authors reviewed the manuscript.

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Correspondence to Younghee Lee.

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Park, S., Jeon, JH., Park, JA. et al. Cleavage of HSP90β induced by histone deacetylase inhibitor and proteasome inhibitor modulates cell growth and apoptosis. Cell Stress and Chaperones 26, 129–139 (2021). https://doi.org/10.1007/s12192-020-01161-6

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