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Multifaceted C-terminus of HSP70-interacting protein regulates tumorigenesis via protein quality control

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Abstract

C-terminus of heat shock protein 70 (HSP70)-interacting protein (CHIP) is an E3 ligase involved in a variety of protein homeostasis events implicated in diverse signaling pathways. Its involvement in varied and even opposite signaling circuits might be due to its hallmark signature of associating with molecular chaperones, including HSP90 and HSP70. Together, these proteins may be pivotal in implementing protein quality control. A curious and puzzling aspect of the function of CHIP is its capability to induce protein degradation via the proteasome- or lysosome-dependent pathways. In addition, these pathways are combined with ubiquitin-dependent or -independent pathways. This review focuses on the role of CHIP in the development or suppression of tumorigenesis. CHIP can act as a tumor suppressor by downregulating various oncogenes. CHIP also displays an oncogenic feature involving the inhibition of diverse tumor suppressors, including proteins related to intrinsic and extrinsic apoptotic pathways. The ability of CHIP to exhibit dual roles in determining the fate of cells has not been studied analytically. However, its association with various proteins involved in protein quality control might play a major role. In this review, the mechanistic roles of CHIP in tumor formation based on the regulation of diverse proteins are discussed.

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Acknowledgements

This work was supported by grants from Creative Research Initiative Program of NRF (2015R1A3A2066581) funded by the Ministry of Science, ICT.

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  1. Jinho Seo and Su Yeon Han contributed equally to this work.

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  1. Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Korea

    Jinho Seo, Su Yeon Han, Daehyeon Seong, Hyun-Ji Han & Jaewhan Song

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  1. Jinho Seo
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  2. Su Yeon Han
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Correspondence to Jaewhan Song.

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Seo, J., Han, S.Y., Seong, D. et al. Multifaceted C-terminus of HSP70-interacting protein regulates tumorigenesis via protein quality control. Arch. Pharm. Res. 42, 63–75 (2019). https://doi.org/10.1007/s12272-018-1101-8

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