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Cited by 128Ubiquitin and proteasome pathwaysNF-κB Signaling PathwaysProtein Degradation and Inhibitors

HECT E3 ubiquitin ligases – emerging insights into their biological roles and disease relevance

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Wang, Yaya, Argiles-Castillo, Diana, Kane, Emma I., Zhou, Anning, Spratt, Donald E.·2020·Journal of Cell Science
DOI 10.1242/jcs.228072PMC PMC7157599
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Abstract

Homologous to E6AP C-terminus (HECT) E3 ubiquitin ligases play a critical role in various cellular pathways, including but not limited to protein trafficking, subcellular localization, innate immune response, viral infections, DNA damage responses and apoptosis. To date, 28 HECT E3 ubiquitin ligases have been identified in humans, and recent studies have begun to reveal how these enzymes control various cellular pathways by catalyzing the post-translational attachment of ubiquitin to their respective substrates. New studies have identified substrates and/or interactors with different members of the HECT E3 ubiquitin ligase family, particularly for E6AP and members of the neuronal precursor cell-expressed developmentally downregulated 4 (NEDD4) family. However, there still remains many unanswered questions about the specific roles that each of the HECT E3 ubiquitin ligases have in maintaining cellular homeostasis. The present Review discusses our current understanding on the biological roles of the HECT E3 ubiquitin ligases in the cell and how they contribute to disease development. Expanded investigations on the molecular basis for how and why the HECT E3 ubiquitin ligases recognize and regulate their intracellular substrates will help to clarify the biochemical mechanisms employed by these important enzymes in ubiquitin biology.

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  • Compared to unaffected Sst supertypes, vulnerable Sst supertypes collectively downregulated specific kinases and E3 ubiquitin ligases.

    “Compared to unaffected Sst supertypes, the vulnerable Sst supertypes collectively downregulated specific kinases (from the tyrosine kinase56 and calcium2+/calmodulin-dependent kinase57 families) (Fig. 5h, green) and E3 ubiquitin ligases (from the homologous to the E6-AP carboxyl terminus (HECT) family58) (Fig. 5h, blue).”

    From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [58]

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Authors
Wang, Y., Argiles-Castillo, D., Kane, E. I., Zhou, A., & Spratt, D. E.
Affiliations
  • Xi'an University of Science and Technology (CN)
  • Clark University (US)
ORCID
Venue
Journal of Cell Science
Publisher
The Company of Biologists
Published
2020-04-01
Volume
133
Issue
7
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
DOI
10.1242/jcs.228072
PMC
PMC7157599
OpenAlex
W3014889276
Cited by
128
References
270
Citations by year
2026: 13 · 2025: 16 · 2024: 25 · 2023: 19 · 2022: 19 · 2021: 30 · 2020: 5
FWCI
1.75
Type
journal article
Language
en
Open access
Licence
www.biologists.com/user-licence-1-1 (vor, 6 d)
Locations
  • Journal of Cell Science (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Clark Digital Commons (Clark University) (submittedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • National Institutes of Health (R15GM126432)
  • Clark University
  • Xi'an University of Science and Technology
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
Keywords
HECT E3 ubiquitin ligase, UBE3A, ubiquitination, protein trafficking, subcellular localization, innate immune response, viral infection, DNA damage response, apoptosis, disease relevance
MeSH terms
Humans, Protein Processing, Post-Translational, Ubiquitin, Ubiquitin-Protein Ligases, Ubiquitination

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