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E3 ubiquitin ligases in cancer and implications for therapies

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Abstract

E3 ligases are a class of enzymes that can transfer ubiquitin to substrates for their degradation, which are of importance in cellular homeostasis. Since many oncogenic or tumor-suppressive proteins are reported to be regulated by the ubiquitin-proteasome system (UPS), E3 ligases, which function as substrate interacting modules, have been attracting more and more attention as promising anticancer drug targets due to their pivotal role in conferring substrate specificity. Generally, based on their molecular structure and functional mechanism, E3 ligases can be divided into three major types: homologous to E6-associated protein C-terminus (HECT), really interesting new gene (RING), and RING-in-between-RING (RBR) E3 ligases. Based on the significance of their functions, more bioactive compounds targeting E3 ligases should be developed in the future. In this review, we discuss the important roles of E3 ligases involved in cancer as well as available bioactive compounds targeting various E3 ligases for potential anticancer activity.

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Funding

This work was supported by the National Natural Sciences Foundation of China (81502065 and 81672926), China Postdoctoral Science Foundation Funded Project (2016T90613, 2015M580574, and 2016M592146), Natural Sciences Foundation of Shandong Province (ZR2014HQ009), Shandong Postdoctoral Innovation Project (201602037), Qingdao Innovation Applied Basic Research Project (16-5-1-56-JCH), and Qingdao Postdoctoral Research Project (2015167 and 2015157).

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  1. Dong Wang and Leina Ma contributed equally to this review.

Authors and Affiliations

  1. Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao, 266021, China

    Dong Wang, Leina Ma & Jia Liu

  2. Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, 266003, China

    Leina Ma

  3. Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA, 02215, USA

    Leina Ma, Bin Wang, Jia Liu & Wenyi Wei

  4. Department of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, China

    Bin Wang

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  1. Dong Wang
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Wang, D., Ma, L., Wang, B. et al. E3 ubiquitin ligases in cancer and implications for therapies. Cancer Metastasis Rev 36, 683–702 (2017). https://doi.org/10.1007/s10555-017-9703-z

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