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Keywords = small HERC family

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17 pages, 1350 KiB  
Review
Regulatory Roles of E3 Ubiquitin Ligases and Deubiquitinases in Bone
by Haotian He, Lifei Wang, Bao Xian and Yayi Xia
Biomolecules 2025, 15(5), 679; https://doi.org/10.3390/biom15050679 - 7 May 2025
Viewed by 909
Abstract
E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) are pivotal regulators of bone homeostasis, orchestrating osteoblast differentiation, proliferation, and osteoclast activity by controlling protein degradation and stability. This review delineates the roles of key E3 ligases (e.g., Smurf1, Smurf2, TRIM family) and DUBs (e.g., [...] Read more.
E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) are pivotal regulators of bone homeostasis, orchestrating osteoblast differentiation, proliferation, and osteoclast activity by controlling protein degradation and stability. This review delineates the roles of key E3 ligases (e.g., Smurf1, Smurf2, TRIM family) and DUBs (e.g., USP family) in bone formation and resorption. E3 ligases such as Smurf1/2 inhibit osteogenesis by degrading BMP/Smad signaling components, while TRIM proteins and HERC ligases promote osteoblast differentiation. Conversely, DUBs like USP2 and USP34 stabilize β-catenin and Smad1/RUNX2, enhancing osteogenic pathways, whereas USP10 and USP12 suppress differentiation. Dysregulation of these enzymes contributes to osteoporosis, fracture non-union, and other bone disorders. The interplay between ubiquitination and deubiquitination, alongside the regulatory role of miRNA and environmental factors, underscores their therapeutic potential. Future research should focus on developing therapies targeting E3 ubiquitin ligases, deubiquitinases, miRNA regulators, and small-molecule inhibitors to restore bone homeostasis in osteoporosis and fracture healing disorders. Full article
(This article belongs to the Section Molecular Medicine)
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18 pages, 3975 KiB  
Article
Zebrafish HERC7c Acts as an Inhibitor of Fish IFN Response
by Yi-Lin Li, Xiu-Ying Gong, Zi-Ling Qu, Xiang Zhao, Cheng Dan, Hao-Yu Sun, Li-Li An, Jian-Fang Gui and Yi-Bing Zhang
Int. J. Mol. Sci. 2023, 24(5), 4592; https://doi.org/10.3390/ijms24054592 - 27 Feb 2023
Cited by 4 | Viewed by 2940
Abstract
In humans, four small HERCs (HERC3-6) exhibit differential degrees of antiviral activity toward HIV-1. Recently we revealed a novel member HERC7 of small HERCs exclusively in non-mammalian vertebrates and varied copies of herc7 genes in distinct fish species, raising a question of what [...] Read more.
In humans, four small HERCs (HERC3-6) exhibit differential degrees of antiviral activity toward HIV-1. Recently we revealed a novel member HERC7 of small HERCs exclusively in non-mammalian vertebrates and varied copies of herc7 genes in distinct fish species, raising a question of what is the exact role for a certain fish herc7 gene. Here, a total of four herc7 genes (named HERC7a–d sequentially) are identified in the zebrafish genome. They are transcriptionally induced by a viral infection, and detailed promoter analyses indicate that zebrafish herc7c is a typical interferon (IFN)-stimulated gene. Overexpression of zebrafish HERC7c promotes SVCV (spring viremia of carp virus) replication in fish cells and concomitantly downregulates cellular IFN response. Mechanistically, zebrafish HERC7c targets STING, MAVS, and IRF7 for protein degradation, thus impairing cellular IFN response. Whereas the recently-identified crucian carp HERC7 has an E3 ligase activity for the conjugation of both ubiquitin and ISG15, zebrafish HERC7c only displays the potential to transfer ubiquitin. Considering the necessity for timely regulation of IFN expression during viral infection, these results together suggest that zebrafish HERC7c is a negative regulator of fish IFN antiviral response. Full article
(This article belongs to the Collection Feature Papers in Molecular Immunology)
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13 pages, 1890 KiB  
Review
HERC Ubiquitin Ligases in Cancer
by Joan Sala-Gaston, Arturo Martinez-Martinez, Leonardo Pedrazza, L. Francisco Lorenzo-Martín, Rubén Caloto, Xosé R. Bustelo, Francesc Ventura and Jose Luis Rosa
Cancers 2020, 12(6), 1653; https://doi.org/10.3390/cancers12061653 - 22 Jun 2020
Cited by 39 | Viewed by 6432
Abstract
HERC proteins are ubiquitin E3 ligases of the HECT family. The HERC subfamily is composed of six members classified by size into large (HERC1 and HERC2) and small (HERC3–HERC6). HERC family ubiquitin ligases regulate important cellular processes, such as neurodevelopment, DNA damage response, [...] Read more.
HERC proteins are ubiquitin E3 ligases of the HECT family. The HERC subfamily is composed of six members classified by size into large (HERC1 and HERC2) and small (HERC3–HERC6). HERC family ubiquitin ligases regulate important cellular processes, such as neurodevelopment, DNA damage response, cell proliferation, cell migration, and immune responses. Accumulating evidence also shows that this family plays critical roles in cancer. In this review, we provide an integrated view of the role of these ligases in cancer, highlighting their bivalent functions as either oncogenes or tumor suppressors, depending on the tumor type. We include a discussion of both the molecular mechanisms involved and the potential therapeutic strategies. Full article
(This article belongs to the Special Issue Targeting the Ubiquitin Pathway in Cancer)
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