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The structure and regulation of the E3 ubiquitin ligase HUWE1 and its biological functions in cancer

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Summary

E3 ligases are a class of critical enzymes that can catalyse the transfer of ubiquitin (Ub) from an E2 enzyme to the substrate and are essential to cellular processes. The E3 ligase HUWE1 (also known as ARF-BP1, HECTH9, HSPC272, Ib772, LASU1, MULE, URE-B1, UREB1, and HECT, UBA and WWE domain-containing E3 ubiquitin protein ligase 1) is encoded by the huwe1 gene. HUWE1 is a key regulator of the DNA damage response, transcription, autophagy, apoptosis and metabolism in a variety of cancers. Due to its pivotal role in conferring substrate specificity, HUWE1 has attracted enormous attention as a promising anticancer drug target. In this review, we indicate the specific molecular structure of HUWE1 and its role in various cellular signalling pathways and highlight new insights into HUWE1 in cancer. Finally, we discuss outstanding questions regarding HUWE1 in oncology and highlight its limitations in drug development and clinical guidance to better define the role of HUWE1 in multiple cancers.

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Funding

This work is funded by the National Natural Science Foundation of China (NO. 81872892 and NO. 81773766), the Natural Science Foundation of Jiangsu Province (NO. BK20181330) and the “Double First-Class” University project (CPU2018GY38).

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Authors and Affiliations

  1. Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu, China

    Xiaofeng Gong, Danyu Du, Yanran Deng, Yuqi Zhou & Li Sun

  2. Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, No. 24, Tongjiaxiang, Nanjing, China

    Shengtao Yuan

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  1. Xiaofeng Gong
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  2. Danyu Du
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  3. Yanran Deng
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  4. Yuqi Zhou
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  5. Li Sun
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Correspondence to Shengtao Yuan.

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Gong, X., Du, D., Deng, Y. et al. The structure and regulation of the E3 ubiquitin ligase HUWE1 and its biological functions in cancer. Invest New Drugs 38, 515–524 (2020). https://doi.org/10.1007/s10637-020-00894-6

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