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Review
. 2020 Jun 30;8(2):71-79.
doi: 10.2478/jtim-2020-0012. eCollection 2020 Jun.

Structure and Function of HECT E3 Ubiquitin Ligases and their Role in Oxidative Stress

Hao Qian  1 , Ying Zhang  1 , Boquan Wu  1 , Shaojun Wu  1 , Shilong You  1 , Naijin Zhang  1 , Yingxian Sun  1
Affiliations
Review

Structure and Function of HECT E3 Ubiquitin Ligases and their Role in Oxidative Stress

Hao Qian et al. J Transl Int Med. .

Abstract

Ubiquitination is a modification after protein transcription that plays a vital role in maintaining the homeostasis of the cellular environment. The Homologous to E6AP C-terminus (HECT) family E3 ubiquitin ligases are a kind of E3 ubiquitin ligases with a C-terminal HECT domain that mediates the binding of ubiquitin to substrate proteins and a variable-length N-terminal extension. HECT-ubiquitinated ligases can be divided into three categories: NEDD4 superfamily, HERC superfamily, and other HECT superfamilies. HECT ubiquitin ligase plays an essential role in the development of many human diseases. In this review, we focus on the physiological and pathological processes involved in oxidative stress and the role of E3 ubiquitin ligase of the HECT family.

Keywords: E3 ubiquitin ligase; oxidative stress; ubiquitination.

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Conflict of interest statement

Conflict of Interest None declared.

Figures

Figure 1
Figure 1
The ubiquitination cascade. The E1 enzyme forms a thioester bond between its active site Cys and the C-terminal Gly of ubiquitin in an ATP-dependent manner. Ubiquitin is then transferred on to the Cys residue in the active site of the E2 enzyme. E2 can bind to E3-ubiquitinated ligase. After activation, E3-ubiquitinated ligase recognizes degraded proteins and links ubiquitin to the substrate.
Figure 2
Figure 2
Classification of the HECT E3 family. The family of HECT E3. All members of the HECT E3 family are characterized by the C-terminal HECT domain, which consists of approximately 350 amino acid residues and represents the catalytic domain. The NEDD4 subfamily has nine members that are characterized by an N-terminal C2 domain and the presence of several WW domains. The HERC family comprises six members, which are characterized by the presence of one or several RLD domains. Members of other HECT E3 subfamily are characterized by the notion that they contain neither RLDs nor WW domains.
Figure 3
Figure 3
Overview of related functions of different HECT E3 ubiquitin ligases under oxidative stress.
See this image and copyright information in PMC

References

    1. Thibaudeau TA, Smith DM. A Practical Review of Proteasome Pharmacology. Pharmacol Rev. 2019;71:170–97. - PMC - PubMed
    1. Soave CL, Guerin T, Liu J, Dou QP. Targeting the ubiquitin-proteasome system for cancer treatment: discovering novel inhibitors from nature and drug repurposing. Cancer Metastasis Rev. 2017;36:717–36. - PMC - PubMed
    1. Xie F, Zhang Z, van Dam H, Zhang L, Zhou F. Regulation of TGF-beta Superfamily Signaling by SMAD Mono-Ubiquitination. Cells. 2014;3:981–93. - PMC - PubMed
    1. Finley D, Ulrich HD, Sommer T, Kaiser P. The ubiquitin-proteasome system of Saccharomyces cerevisiae. Genetics. 2012;192:319–60. - PMC - PubMed
    1. Nandi D, Tahiliani P, Kumar A, Chandu D. The ubiquitin-proteasome system. J Biosci. 2006;31:137–55. - PubMed

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