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Kelch-like protein 3 in human disease and therapy

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Abstract

Kelch-like protein 3 (KLHL3) is a substrate adaptor of Cullin3-RING ubiquitin ligase (CRL3), and KLHL3-CUL3 complex plays a vital role in the ubiquitination of specific substrates. Mutations and abnormal post-translational modifications of KLHL3-CUL3 affect substrate ubiquitination and may related to the pathogenesis of Gordon syndrome (GS), Primary Hyperparathyroidism (PHPT), Diabetes Mellitus (DM), Congenital Heart Disease (CHD), Pre-eclampsia (PE) and even cancers. Therefore, it is essential to understand the function and molecular mechanisms of KLHL3-CUL3 for the treatment of related diseases. In this review, we summary the structure and function of KLHL3-CUL3, the effect of KLHL3-CUL3 mutations and aberrant modifications in GS, PHPT, DM, CHD and PE. Moreover, we noted a possible role of KLHL3-CUL3 in carcinogenesis and provided ideas for targeting KLHL3-CUL3 for related disease treatment.

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Acknowledgements

We would like to thank Dr. Yuqi Wang (West Lake University, China) for the kind help and good advice provided.

Funding

This work was supported by The Natural Science Foundation of Ningbo (grant no. 2021J065), and The K.C. Wong Magna Fund of Ningbo University.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, 315211, Ningbo, China

    Yan Lin, Qian Li & Xiaofeng Jin

  2. The Affiliated Hospital of Medical School, Ningbo University, 315020, Ningbo, China

    Yan Lin, Qian Li & Xiaofeng Jin

Authors
  1. Yan Lin
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  2. Qian Li
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  3. Xiaofeng Jin
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Contributions

YL and QL drafted the manuscript. XJ, QL and YL made substantial contributions to the interpretation, drafting the study and revising it critically for important intellectual content. XJ, and YL were major contributors in the manuscript. All authors read and approved the fnal manuscript. Data authentication is not applicable.

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Correspondence to Xiaofeng Jin.

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Lin, Y., Li, Q. & Jin, X. Kelch-like protein 3 in human disease and therapy. Mol Biol Rep 49, 9813–9824 (2022). https://doi.org/10.1007/s11033-022-07487-x

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  • DOI: https://doi.org/10.1007/s11033-022-07487-x

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