scholarly journals A novel frameshift mutation in ubiquitin-specific protease 26 gene in a patient with severe oligozoospermia

2020 ◽  
Vol 40 (4) ◽  
Author(s):  
Leilei Li ◽  
Qi Xi ◽  
Hongguo Zhang ◽  
Jia Fei ◽  
Yuting Jiang ◽  
...  
Keyword(s):  
Male Infertility ◽  
Frameshift Mutation ◽  
Bioinformatics Analysis ◽  
Chinese Patient ◽  
Deubiquitinating Enzyme ◽  
Deubiquitinating Enzymes ◽  
Severe Oligozoospermia ◽  
Specific Protease ◽  
Ubiquitin Specific Protease ◽  
Testis Tissue

Abstract Ubiquitin-specific protease 26 (USP26) encodes a predicted protein containing his- and cys- domains that are conserved among deubiquitinating enzymes. USP26 is specifically expressed in testis tissue and is a potential infertility gene. In the present study, we performed genetic testing related to spermatogenesis impairment in a patient with idiopathic severe oligozoospermia to identify the cause. The patient underwent clinical examination and reproductive hormone testing. Genes associated with male infertility, including USP26, were assessed by targeted exome sequencing. A novel frameshift mutation, c.2195delT (p.Phe732Serfs*14), was identified in USP26. This frameshift mutation was located in residue 732 of USP26 gene, leading to loss of the conserved deubiquitinating enzyme His-domain and producing a truncated protein of 744 amino acids. Bioinformatics analysis revealed this mutation to be pathogenic. A novel framshift mutation c.2195delT (p.Phe732Serfs*14) in USP26 gene was reported to be associated with male infertility in a Chinese patient with severe oligozoospermia.

scholarly journals USP19 is a ubiquitin-specific protease regulated in rat skeletal muscle during catabolic states

2005 ◽  
Vol 288 (4) ◽  
pp. E693-E700 ◽  
Author(s):  
Lydie Combaret ◽  
Olasunkanmi A. J. Adegoke ◽  
Nathalie Bedard ◽  
Vickie Baracos ◽  
Didier Attaix ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
De Novo ◽  
Deubiquitinating Enzyme ◽  
Mrna Levels ◽  
Deubiquitinating Enzymes ◽  
Rat Skeletal Muscle ◽  
Ubiquitin System ◽  
Specific Protease ◽  
Ubiquitin Specific Protease

Ubiquitin-dependent proteolysis is activated in skeletal muscle atrophying in response to various catabolic stimuli. Previous studies have demonstrated activation of ubiquitin conjugation. Because ubiquitination can also be regulated by deubiquitinating enzymes, we used degenerate oligonucleotides derived from conserved sequences in the ubiquitin-specific protease (UBP) family of deubiquitinating enzymes in RT-PCR with skeletal muscle RNA to amplify putative deubiquitinating enzymes. We identified USP19, a 150-kDa deubiquitinating enzyme that is widely expressed in various tissues including skeletal muscle. Expression of USP19 mRNA increased by ∼30–200% in rat skeletal muscle atrophying in response to fasting, streptozotocin-induced diabetes, dexamethasone treatment, and cancer. Increased mRNA levels during fasting returned to normal with refeeding, but 1 day later than the normalization of rates of proteolysis and coincided instead with recovery of muscle mass. Indeed, in all catabolic treatments, USP19 mRNA was inversely correlated with muscle mass and provided an index of muscle mass that may be useful in many pathological conditions, using small human muscle biopsies. The increased expression of this deubiquitinating enzyme under conditions of increased proteolysis suggests that it may play a role in regeneration of free ubiquitin either coincident with or after proteasome-mediated degradation of substrates. USP19 may also be involved in posttranslational processing of polyubiquitin produced de novo in response to induction of the polyubiquitin genes seen under these conditions. Deubiquitinating enzymes thus appear involved in muscle wasting and implicate a widening web of regulation of genes in the ubiquitin system in this process.

scholarly journals The role of the deubiquitinating enzyme DUB3/USP17 in cancer: a narrative review

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guang-Fei Yang ◽  
Xin Zhang ◽  
Yi-Ge Su ◽  
Ren Zhao ◽  
Yan-Yang Wang
Keyword(s):  
Central Nervous System ◽  
Cancer Research ◽  
Soft Tissue Sarcomas ◽  
Regulatory Mechanisms ◽  
Deubiquitinating Enzyme ◽  
Biological Functions ◽  
Deubiquitinating Enzymes ◽  
Specific Protease ◽  
Ubiquitin Specific Protease

AbstractThe balance between ubiquitination and deubiquitination is critical for the degradation, transport, localization, and activity of proteins. Deubiquitinating enzymes (DUBs) greatly contribute to the balance of ubiquitination and deubiquitination, and they have been widely studied due to their fundamental role in cancer. DUB3/ubiquitin-specific protease 17 (USP17) is a type of DUB that has attracted much attention in cancer research. In this review, we summarize the biological functions and regulatory mechanisms of USP17 in central nervous system, head and neck, thoracic, breast, gastrointestinal, genitourinary, and gynecologic cancers as well as bone and soft tissue sarcomas, and we provide new insights into how USP17 can be used in the management of cancer.

scholarly journals Emerging Roles of Ubiquitin-Specific Protease 25 in Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Wenjing Zhu ◽  
Dandan Zheng ◽  
Dandan Wang ◽  
Lehe Yang ◽  
Chengguang Zhao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infections ◽  
Disease Onset ◽  
Mechanisms Of Action ◽  
Deubiquitinating Enzyme ◽  
Deubiquitinating Enzymes ◽  
Specific Protease ◽  
Ubiquitin Specific Protease ◽  
Similarities And Differences

The balance of ubiquitination and deubiquitination plays diverse roles in regulating protein stability and cellular homeostasis. Deubiquitinating enzymes catalyze the hydrolysis and removal of ubiquitin chains from target proteins and play critical roles in various disease processes, including cancer, immune responses to viral infections and neurodegeneration. This article aims to summarize roles of the deubiquitinating enzyme ubiquitin-specific protease 25 (USP25) in disease onset and progression. Previous studies have focused on the role of USP25 in antiviral immunity and neurodegenerative diseases. Recently, however, as the structural similarities and differences between USP25 and its homolog USP28 have become clear, mechanisms of action of USP25 in cancer and other diseases have been gradually revealed.

USP48 Sustains Chemoresistance and Metastasis in Ovarian Cancer

2020 ◽  
Vol 20 (9) ◽  
pp. 689-699
Author(s):  
Xuemeng Lei ◽  
Xukun Li ◽  
Hongyan Chen ◽  
Zhihua Liu
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Migration And Invasion ◽  
Clinical Samples ◽  
Deubiquitinating Enzymes ◽  
Potential Therapeutic Target ◽  
Kaplan Meier ◽  
Specific Protease ◽  
Ubiquitin Specific Protease

Background: Ubiquitin specific protease 48 (USP48) is a member of the deubiquitinating enzymes (DUBs) family. However, the function of USP48 in ovarian cancer remains unclear. Objective: The present study reveals that USP48 knockdown could significantly inhibit cell migration and invasion in ES2, 3AO and A2780 cells, without affecting cell proliferation. Methods: After carboplatin (CBP) treatment, the USP48 ablation increases the apoptosis rate, and the cleaved PARP and cleaved caspase 3 expression levels in ES2, 3AO and A2780 cells. The subcutaneous tumor and intraperitoneally injected experiments demonstrated that the USP48 knockdown significantly increases responsiveness to CBP, and alleviates the metastasis in vivo. Meanwhile, USP48 deficiency results in the improved survival of mice. Results: Finally, the analysis of clinical samples and the TCGA and Kaplan-Meier Plot database revealed that the high expression of USP48 in ovarian cancer patients is associated with poor survival and resistance to CBP therapy. Conclusion: In summary, USP48 may be a potential therapeutic target for ovarian cancer patients.

scholarly journals Novel mutations in ubiquitin-specific protease 26 gene might cause spermatogenesis impairment and male infertility

2007 ◽  
Vol 9 (6) ◽  
pp. 809-814 ◽  
Author(s):  
Jie Zhang ◽  
Shu-Dong Qiu ◽  
Sheng-Bin Li ◽  
Dang-Xia Zhou ◽  
Hong Tian ◽  
...  
Keyword(s):  
Male Infertility ◽  
Novel Mutations ◽  
Specific Protease ◽  
Ubiquitin Specific Protease ◽  
Spermatogenesis Impairment

scholarly journals Deubiquitinating Enzyme USP8 Is Essential for Skeletogenesis by Regulating Wnt Signaling

2021 ◽  
Vol 22 (19) ◽  
pp. 10289
Author(s):  
Sachin Chaugule ◽  
Jung-Min Kim ◽  
Yeon-Suk Yang ◽  
Klaus-Peter Knobeloch ◽  
Xi He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Skeletal Development ◽  
Fine Tuning ◽  
Osteogenic Potential ◽  
Deubiquitinating Enzyme ◽  
Renal Capsule ◽  
Wild Type ◽  
Lysosomal Degradation ◽  
Specific Protease ◽  
Ubiquitin Specific Protease

Disturbance in a differentiation program of skeletal stem cells leads to indecorous skeletogenesis. Growing evidence suggests that a fine-tuning of ubiquitin-mediated protein degradation is crucial for skeletal stem cells to maintain their stemness and osteogenic potential. Here, we demonstrate that the deubiquitinating enzyme (DUB) ubiquitin-specific protease 8 (USP8) stabilizes the Wnt receptor frizzled 5 (FZD5) by preventing its lysosomal degradation. This pathway is essential for Wnt/β-catenin signaling and the differentiation of osteoprogenitors to mature osteoblasts. Accordingly, deletion of USP8 in osteoprogenitors (Usp8Osx) resulted in a near-complete blockade in skeletal mineralization, similar to that seen in mice with defective Wnt/β-catenin signaling. Likewise, transplanting USP8-deficient osteoprogenitors under the renal capsule in wild-type secondary hosts did not to induce bone formation. Collectively, this study unveils an essential role for the DUB USP8 in Wnt/β-catenin signaling in osteoprogenitors and osteogenesis during skeletal development.

Association between ubiquitin-specific protease USP26 polymorphism and male infertility in Chinese men

2011 ◽  
Vol 412 (7-8) ◽  
pp. 545-549 ◽  
Author(s):  
Yi-chao Shi ◽  
Li Wei ◽  
Ying-xia Cui ◽  
Xue-jun Shang ◽  
Hao-yang Wang ◽  
...  
Keyword(s):  
Male Infertility ◽  
Chinese Men ◽  
Specific Protease ◽  
Ubiquitin Specific Protease

scholarly journals The ubiquitin-specific protease USP8 deubiquitinates and stabilizes Cx43

2018 ◽  
Vol 293 (21) ◽  
pp. 8275-8284 ◽  
Author(s):  
Jian Sun ◽  
Qianwen Hu ◽  
Hong Peng ◽  
Cheng Peng ◽  
Liheng Zhou ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Cultured Cells ◽  
Deubiquitinating Enzyme ◽  
Human Breast ◽  
Dye Transfer ◽  
Protein Levels ◽  
Mammalian Tissues ◽  
Specific Protease ◽  
Bona Fide ◽  
Ubiquitin Specific Protease

Connexin-43 (Cx43, also known as GJA1) is the most ubiquitously expressed connexin isoform in mammalian tissues. It forms intercellular gap junction (GJ) channels, enabling adjacent cells to communicate both electrically and metabolically. Cx43 is a short-lived protein which can be quickly degraded by the ubiquitin-dependent proteasomal, endolysosomal, and autophagosomal pathways. Here, we report that the ubiquitin-specific peptidase 8 (USP8) interacts with and deubiquitinates Cx43. USP8 reduces both multiple monoubiquitination and polyubiquitination of Cx43 to prevent autophagy-mediated degradation. Consistently, knockdown of USP8 results in decreased Cx43 protein levels in cultured cells and suppresses intercellular communication, revealed by the dye transfer assay. In human breast cancer specimens, the expression levels of USP8 and Cx43 proteins are positively correlated. Taken together, these results identified USP8 as a crucial and bona fide deubiquitinating enzyme involved in autophagy-mediated degradation of Cx43.

Sign in / Sign up

Export Citation Format

Share Document