Ask about this productRelated genes to: Usp10 antibody
- Gene:
- USP10 NIH gene
- Name:
- ubiquitin specific peptidase 10
- Previous symbol:
- -
- Synonyms:
- UBPO, KIAA0190
- Chromosome:
- 16q24.1
- Locus Type:
- gene with protein product
- Date approved:
- 1999-02-01
- Date modifiied:
- 2016-01-15
Related products to: Usp10 antibody
Related articles to: Usp10 antibody
- Oxaliplatin (OXA) is widely used to treat advanced gastric cancer, but acquired resistance limits its benefit. How resistant cells avoid ferroptosis remains unclear. Quantitative proteomics identified UGT8, a glycosphingolipid biosynthetic enzyme, as an upregulated protein in OXA-resistant gastric cancer cells. UGT8 protein was also increased in tumors from clinically OXA-resistant patients treated with oxaliplatin-based chemotherapy, and high UGT8 expression was associated with shorter survival. UGT8 overexpression increased OXA tolerance, while UGT8 depletion sensitized resistant cells and patient-derived organoids (PDOs) from clinically OXA-resistant patients to OXA. UGT8 depletion increased lipid reactive oxygen species and malondialdehyde, reduced glutathione, and aggravated ferroptosis-associated mitochondrial damage. Immunoprecipitation followed by mass spectrometry identified USP10 as a UGT8-associated protein. USP10 increased UGT8 stability and limited its K48-linked polyubiquitination. K307 was identified by mutational analysis as a functionally important residue involved in USP10-regulated UGT8 ubiquitination. UGT8 increased NRF2 nuclear accumulation and maintained HO-1, SLC7A11, and GPX4 expression. Restoring UGT8 or pharmacologically enhancing NRF2-associated antioxidant signaling reduced the effects of USP10 or UGT8 depletion on OXA sensitivity and ferroptosis-associated changes. Disrupting the USP10-UGT8 pathway also improved the OXA response in xenografts. These results support a role for USP10-dependent UGT8 stabilization in sustaining NRF2-associated antioxidant signaling, suppressing ferroptosis, and promoting OXA resistance. - Source: PubMed
Publication date: 2026/08/26
Gan JinhengZou YonghuiXu HesongFan LuojunLeng WenmingLi KongLiu QiChen YangLi YifanXin Lin - The RNA binding G3BP1 is depleted in several neurodegenerative diseases, yet its functional consequences at the cellular level remain poorly understood. While best known for its critical role in stress granule formation, we demonstrate that G3BP1 also stabilises the COPI vesicle protein beta-COP by promoting its interaction with the deubiquitinase USP10. G3BP1 depletion disrupts this interaction leading to increased ubiquitination of beta-COP, which accelerates its proteasomal degradation. This leads to compromised Golgi structure and function, and impaired lysosomal homeostasis, which causes defective autophagic flux. Consequently, the autophagic clearance of α-synuclein, a protein that can drive Parkinson's disease (PD), is significantly slowed. Importantly, we observe a concurrent reduction of both G3BP1 and beta-COP protein levels in brain sections from PD and dementia with Lewy Body (DLB) patients and from a PD mouse model. These findings reveal a novel mechanistic link between G3BP1, vesicular trafficking, and proteostasis in neurodegeneration. - Source: PubMed
Publication date: 2026/08/26
Ramakrishna SarayuRyan LauraSon Sung MinRubinsztein David C - Atrial fibrillation (AF) contributes to cardiovascular morbidity and mortality. Ubiquitin-specific peptidase 10 (USP10) plays a crucial role in numerous cellular processes; however, its particular role in AF remains largely unexplored. In the present study, USP10 expression was assessed in human atrial samples and angiotensin II-treated (Ang II-treated) mouse atrial tissues. An Ang II-induced AF mouse model was employed to investigate the effects of USP10 on atrial remodeling and AF susceptibility. Calcium imaging and patch clamp techniques were used to evaluate USP10's influence on calcium handling and triggered activity. Additionally, RNA sequencing, coimmunoprecipitation, and ubiquitination assays were performed to explore the regulatory interactions between USP10 and NADH:ubiquinone oxidoreductase subunit S1 (NDUFS1). Our findings demonstrate that USP10 is downregulated in atrial tissues from mouse models and patients with AF. USP10 overexpression counteracts Ang II-induced atrial remodeling and reduces AF susceptibility. Furthermore, USP10 contributes to the restoration of mitochondrial function in AF. Mechanistically, USP10 deubiquitinates NDUFS1 at lysine 621, stabilizing NDUFS1 protein levels and mitigating Ang II-induced mitochondrial dysfunction. This study uncovers a critical mechanistic link between USP10 and NDUFS1. Our findings suggest that upregulating USP10 or targeting NDUFS1 degradation could provide an alternative therapeutic strategy to mitigate AF progression and associated cardiovascular risk. - Source: PubMed
Publication date: 2026/08/24
Fu WanrongTian Xiao-XuZhou JianghuaHuang Yu-XuLi HuanWang ZhenyaWei Tong-You WadeLi LiZhao Guo-Jun - Oral submucous fibrosis (OSF) is a chronic, progressive, premalignant disorder with expanding epidemiology, rising annual incidence, and increasing malignant transformation rates. Therefore, elucidating its pathogenesis and establishing early intervention strategies remain urgent priorities. In this study, we evaluated the interplay between USP10 and IL-6 and its potential influence on the development of oral submucous fibrosis. Immunohistochemistry and immunofluorescence were used to examine the correlation among IL-6, USP10, and pathological angiogenesis in OSF clinical samples and mouse models, revealing high IL-6 expression in the inflammatory microvasculature alongside downregulated USP10. Functional experiments on human umbilical vein endothelial cells (HUVECs) in vitro, including administration of recombinant human IL-6, demonstrated that USP10 inhibited angiogenesis, cell migration, and cell proliferation, and that targeting USP10 reversed IL-6-mediated pathological angiogenesis. RNA sequencing further identified differentially expressed genes in HUVECs, while mass spectrometry, western blotting, and co-immunoprecipitation uncovered that USP10 interacts with vascular endothelial growth factor receptor 1 (VEGFR1) and inhibits its ubiquitination, thereby suppressing angiogenesis. Collectively, these findings indicate that IL-6 promotes pathological angiogenesis by suppressing USP10 and its interaction with VEGFR1, thus accelerating OSF progression, and suggest that targeting USP10 may represent a promising mechanism for further investigation in OSF therapy. - Source: PubMed
Li ChunyuHan LingshuangWang ZhenhaoXie YihangXu XiaopingChen QianmingXie Liang - The progressive loss of midbrain dopamine neurons leading to motor deficits is the primary cause of Parkinson's disease (PD). Emerging reports on the role of NURR1 in the differentiation and maintenance of dopamine neurons; the association of reduced levels/familial mutants of NURR1 in PD subjects makes it a promising candidate for developing novel therapeutics. In the present study, while examining the effects of known deubiquitinase inhibitors, we have identified that the USP10/13 inhibitor, spautin-1, upregulated NURR1 levels in a transcription-dependent manner. Further, USP13, but not USP10, was found to be essential in spautin-1-mediated NURR1 regulation. Reports indicate that USP13 deubiquitinates SKP2 and thereby prevents it from degradation. Also, SKP2 is an E3 ligase for P57/kip2 and reduced SKP2 expression leads to enhanced P57/kip2 levels. In line with the above findings, cells treated with spautin-1 exhibited reduced SKP2 with a concomitant increase in P57/kip2 levels. Our results indicate that spautin-1-mediated regulation of the USP13-SKP2-P57/kip2 axis could play a crucial role in NURR1 upregulation since overexpression of SKP2, or knockdown of P57/kip2, abrogated spautin-1-mediated effects. Further, spautin-1 mediated neurite outgrowth of dopaminergic cells was mitigated under NURR1 knockdown conditions, indicating that small molecule activators of NURR1 could promote neurite outgrowth. Lastly, the ability of spautin-1 in enhancing tyrosine hydroxylase staining in vivo in PD mouse model suggests that pharmacological activation of NURR1 could mitigate biochemical manifestations of PD. - Source: PubMed
Edward AnnaPuttapaka Srinivas NVulli AravindKalivendi Shasi V