BAP1 Tumor Predisposition Syndrome
Dongyou Liu in Handbook of Tumor Syndromes, 2020
Mutations in the BAP1 gene may produce prematurely terminated BAP1 protein, reduce cellular BAP1 levels, and alter the ubiquitin carboxyl-terminal hydrolase domain, thus affecting the deubiquitinase activity of BAP1. Reduced nuclear and cytoplasmic activities of BAP1 decrease IP3R3 levels and Ca2+ flux, and prevent cells containing damaged DNA from apoptosis. There is evidence that carriers of germline BAP1 mutations with only one normal BAP1 allele have 50% less of cellular BAP1 than normal persons. Furthermore, cells from carriers of germline BAP1 mutations display reduced ability to repair DNA by homologous recombination (due to the reduced nuclear BAP1 levels) and impaired apoptosis upon exposure to asbestos, ultraviolet light, and irradiation (due to the reduced mitochondrial Ca2+ levels), leading to increased vulnerability to malignant transformation [24].
The mitotic phase of spermatogenesis
C. Yan Cheng in Spermatogenesis, 2018
In the mitotic division of spermatogonia, it has been proposed that both symmetric and asymmetric division occurs. Symmetric division allows the stem cell to become two stem cells or two committed progenies while asymmetric division allows the stem cell to give rise to a stem cell and a committed progeny.9 The asymmetric segregation of cell fate determinant could be one plausible mechanism for determining the identity of progenies.9 The deubiquitinating enzyme UCH-L1 is expressed in spermatogonia and asymmetrically distributed to the two progenies in the asymmetric division of spermatogonia. A higher level of UCH-L1 is observed in Plzf+ Aundiff spermatogonia whereas c-Kit+ differentiating spermatogonia inherit low/undetectable level of UCH-L1.77 This result suggests that UCH-L1 may be involved in regulating the self-renewal and differentiation of spermatogonia.
Human Noroviruses
Dongyou Liu in Handbook of Foodborne Diseases, 2018
Besides the traditional approaches, interferons (peptides with antiviral activity) as viable approaches to combat HNoV infection are being researched as summarized in Prasad et al.221 Type I interferons are reported to inhibit HNoV replication in a replicon system in vitro, without any reports on human studies, while both type I and type II interferons can inhibit MNV replication and type III interferon, interferon lambda, can clear chronic MNV infection.244,245 RNA interference model studies that prevent HNoV replication and design of deubiquitinase inhibitors that target host factors during the viral life cycle are other research avenues.221,222 It appears that the combined use of antivirals and vaccines may be needed to prevent the spread of emerging HNoVs or to alleviate their disease symptoms or both.221
The role of plant expression platforms in biopharmaceutical development: possibilities for the future
Published in Expert Review of Vaccines, 2019
Other Zoonotic diseases such as Chikungunya and Middle Eastern Respiratory syndrome virus are also being addressed using plant-based approaches. Chikungunya is a mosquito-transmitted virus that causes fever, headaches and severe joint pain. Multiple efforts have been made to generate a plant-made vaccine to Chikungunya with some success [46,47]. Monoclonal antibodies to Chikungunya virus have been successfully constructed and used both as a diagnostic tool and as a therapeutic for the poor [48]. Similarly, MERS, which is endemic in the world’s camel population, transmitted by aerosol and, with a mortality rate in humans approaching 40%, has been designated as a potential emerging threat [49]. A plant-made version of a ubiquitin variant, which binds to the viral deubiquitinase enzyme and blocks infection, has been constructed in several virus expression systems and is currently being explored as an efficacious means to block transmission as well as disease symptoms (personal communication).
Concentration of UHCL1 in the Serum of Children with Acute Appendicitis, Before and After Surgery, and Its Correlation with CRP and Prealbumin
Published in Journal of Investigative Surgery, 2018
Ewa Matuszczak, Marzena Tylicka, Wojciech Dębek, Anna Tokarzewicz, Ewa Gorodkiewicz, Adam Hermanowicz
UCHL1 acts as a free ubiquitin stabilizer, providing ready-to-use ubiquitin for various cellular events [1–4]. The net ubiquitination status of any protein is regulated both through the processes of attachment and detachment with alterations of either event leading to changes in the half-life or biochemical function of targeted proteins, and UCHL1 is able to function as both a ubiquitin ligase and deubiquitinase [1–4]. The function of UCHL1 probably varies in a cell and environmental specific manner. UCHL1 exerts its effects by influencing levels of free proteins such as cellular ubiquitin, glutathione and by regulation of the cell cycle [1–4]. Previous studies report on UCHL1 as a possible plasma biomarker for ischemic and traumatic brain injury in rodents and traumatic brain injury in humans [20]. UCHL1 is also highly expressed in carcinomas of various tissue origins, including those from brain, lung, breast, kidney, colon, prostate, pancreas, and mesenchymal tissues [1–4]. Loss-of-function studies and an inhibitor for UCHL1 confirmed the importance of UCHL1 for cancer therapy. Moreover, expression levels of UCHL1 in breast and lung cancers were found to be associated with those of HIF-1a and poor prognosis in cancer patients [4]. Previous studies shown that UCHL1 is involved in tumor metastases [6, 21–22].
Bone Marrow Stromal Cell-Secreted Extracellular Vesicles Containing miR-34c-5p Alleviate Lung Injury and Inflammation in Bronchopulmonary Dysplasia Through Promotion of PTEN Degradation by Targeting OTUD3
Published in Immunological Investigations, 2023
Xiao He, Juan Kuang, Yijing Wang, Guofeng Lan, Xuekai Shi
The Starbase database utilized in our study predicted that ovarian tumor deubiquitinase 3 (OTUD3) bound to miR-34c-5p. OTUD3, a deubiquitinase, can stabilize proteins by deubiquitinating K48-linked ubiquitination and modulate protein activity by deubiquitinating K11- or K63-linked ubiquitination (Shen et al. 2021). Reportedly, OTUD3 suppressed tumorigenesis by promoting the stability of phosphatase and tensin homolog (PTEN) through deubiquitination (Yuan et al. 2015). Moreover, PTEN downregulation participates in the repressive impacts of microvesicles from human umbilical cord MSCs on alveolarization and lung inflammation in BPD rats (Zhou et al. 2022). These backgrounds contribute to the hypothesis that BMSC-EVs containing miR-34c-5p (BMSC-EVs-miR-34c-5p) might affect BPD progression through the OTUD3/PTEN axis. Therefore, this study was designed to confirm this speculation, providing a novel therapeutic direction for BPD.
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