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Keywords = HERC7 subfamily

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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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14 pages, 3356 KiB  
Article
The Giant HECT E3 Ubiquitin Ligase HERC1 Is Aberrantly Expressed in Myeloid Related Disorders and It Is a Novel BCR-ABL1 Binding Partner
by Muhammad Shahzad Ali, Cristina Panuzzo, Chiara Calabrese, Alessandro Maglione, Rocco Piazza, Daniela Cilloni, Giuseppe Saglio, Barbara Pergolizzi and Enrico Bracco
Cancers 2021, 13(2), 341; https://doi.org/10.3390/cancers13020341 - 19 Jan 2021
Cited by 9 | Viewed by 4845
Abstract
HERC E3 subfamily members are parts of the E3 ubiquitin ligases and key players for a wide range of cellular functions. Though the involvement of the Ubiquitin Proteasome System in blood disorders has been broadly studied, so far the role of large HERCs [...] Read more.
HERC E3 subfamily members are parts of the E3 ubiquitin ligases and key players for a wide range of cellular functions. Though the involvement of the Ubiquitin Proteasome System in blood disorders has been broadly studied, so far the role of large HERCs in this context remains unexplored. In the present study we examined the expression of the large HECT E3 Ubiquitin Ligase, HERC1, in blood disorders. Our findings revealed that HERC1 gene expression was severely downregulated both in acute and in chronic myelogenous leukemia at diagnosis, while it is restored after complete remission achievement. Instead, in Philadelphia the negative myeloproliferative neoplasm HERC1 level was peculiarly controlled, being very low in Primary Myelofibrosis and significantly upregulated in those Essential Thrombocytemia specimens harboring the mutation in the calreticulin gene. Remarkably, in CML cells HERC1 mRNA level was associated with the BCR-ABL1 kinase activity and the HERC1 protein physically interacted with BCR-ABL1. Furthermore, we found that HERC1 was directly tyrosine phosphorylated by the ABL kinase. Overall and for the first time, we provide original evidence on the potential tumor-suppressing or -promoting properties, depending on the context, of HERC1 in myeloid related blood disorders. Full article
(This article belongs to the Special Issue The Role of the Ubiquitin-Proteasome-System in Human Cancer)
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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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