The HECT Family of E3 Ubiquitin Ligases: Multiple Players in Cancer Development
Open accessAbstract
The involvement of the homologous to E6-AP carboxyl terminus (HECT)-type E3s in crucial signaling pathways implicated in tumorigenesis is presently an area of intense research and extensive scientific interest. This review highlights recent discoveries on the ubiquitin-mediated degradation of crucial tumor suppressor molecules catalyzed by the HECT-type E3s. By providing a portrait of their protein targets, we intend to link the substrate specificity of HECT-type E3s with their contribution to tumorigenesis. Moreover, we discuss the relevance of targeting the HECT E3s, through the development of small-molecule inhibitors, as an anticancer therapeutic strategy.
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The selection of substrates for ubiquitination rests primarily with E3s.
“The selection of substrates for ubiquitination appears to rest primarily with E3s, and two major families are known: those that contain RING domains (9), and those that contain HECT domains (10).”
From RNF170 Protein, an Endoplasmic Reticulum Membrane Ubiquitin Ligase, Mediates Inositol 1,4,5-Trisphosphate Receptor Ubiquitination and Degradation (2011) · cites this paper as [10]
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- Authors
- Bernassola, F., Karin, M., Ciechanover, A., & Melino, G.
- Affiliations
- University of Rome Tor Vergata (IT)
- University of California San Diego (US)
- Technion – Israel Institute of Technology (IL)
- Corresponding author
- Melino, Gerry
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2008-07
- Volume
- 14
- Issue
- 1
- Pages
- 10-21
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2067343115
- Cited by
- 541
- References
- 3
- Citations by year
- 2026: 5 · 2025: 15 · 2024: 18 · 2023: 36 · 2022: 22 · 2021: 43 · 2020: 30 · 2019: 31 · 2018: 26 · 2017: 32 · 2016: 34 · 2015: 40 · 2014: 45 · 2013: 32 · 2012: 39
- FWCI
- 2.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Keywords
- HECT E3 ubiquitin ligase, E3 ubiquitin ligase, ubiquitin-mediated proteolysis, tumor suppressor proteins, carcinogenesis, substrate specificity, small molecule inhibitors, anticancer agents
- MeSH terms
- Nedd4 Ubiquitin Protein Ligases, Animals, Antineoplastic Agents, Cell Transformation, Neoplastic, Enzyme Inhibitors, Humans, Neoplasms, Repressor Proteins, Substrate Specificity, Signal Transduction, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Tumor Suppressor Proteins, Ubiquitin, Ubiquitin-Protein Ligases, Endosomal Sorting Complexes Required for Transport
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