Ask about this productRelated genes to: USP11 antibody
- Gene:
- USP11 NIH gene
- Name:
- ubiquitin specific peptidase 11
- Previous symbol:
- -
- Synonyms:
- UHX1
- Chromosome:
- Xp11.3
- Locus Type:
- gene with protein product
- Date approved:
- 1999-02-01
- Date modifiied:
- 2016-10-05
Related products to: USP11 antibody
Related articles to: USP11 antibody
- Oxidative stress is identified as a potential factor in vitiligo pathogenesis. We aimed here to evaluate whether USP11 regulates the oxidative stress of melanocytes in vitiligo. Human melanocyte PIG1 cells were induced with 1 mM HO and pre-infected with lentiviruses for genetic intervention. The dorsal skin of C57BL/6J mice was applied with 5% HO, and genetic intervention was elicited through adenoviruses. USP11, SIRT3, and TRIM28 were reduced in melanocytes (Melan-A positive) from vitiligo mouse skin tissues and in the HO-induced PIG1 cells. TRIM28 transcriptionally activated USP11 to promote deubiquitination of SIRT3. HO decreased viability and melanin and tyrosinase contents and increased apoptosis and oxidative stress in PIG1 cells. HO induced severe depigmentation of the dorsal skin in mice, reduced melanin deposition in hair follicles, loss of melanocytes, and increased oxidative stress. Overexpression of either USP11 or TRIM28 inhibited HO-induced melanocyte damage and vitiligo, while combined knockdown of SIRT3 or USP11 reversed the effects of USP11 or TRIM28 overexpression. These findings suggest that TRIM28 exerts its effect by reducing oxidative stress in melanocytes through USP11-mediated SIRT3 deubiquitination. This observation provides a mechanistic insight that could inform future therapeutic exploration in vitiligo. Graphical abstract text. The diagram. TRIM28 inhibits oxidative stress damage in melanocytes and alleviates vitiligo by transcriptionally upregulating USP11 and promoting deubiquitination modification of SIRT3. - Source: PubMed
Nie XiaojuanLi YuanyuanYuan LingSun Mingxia - Colorectal cancer (CRC) remains one of the most common and deadly malignancies, with limited effective treatment options. Cuproptosis is a novel regulated cell death triggered by mitochondrial copper overload (Cu) and has been implicated in several cancers. However, the mechanisms governing cuproptosis in CRC are largely unknown. In this study, we investigated the role of ubiquitin-specific proteases (USPs), key regulators of protein stability, in modulating cuproptosis in CRC. Through integrative analysis of publicly available CRC transcriptomic datasets, we identified oncogenic USPs potentially involved in cuproptosis regulation. Among them, USP11 emerged as significantly overexpressed in CRC tissues, and its elevated expression was correlated with poorer patient survival. We next examined the functional role of USP11 in two CRC cell lines and patient-derived CRC organoids. Cells were treated with elesclomol and CuCl, a combination known to induce cuproptosis. Functional assays revealed that USP11 promotes cell viability, colony formation, survival, and migration/invasion and suppresses cuproptosis in response to treatment. Mechanistic studies showed that USP11 directly binds to and deubiquitinates ISCU, a scaffold protein essential for iron-sulfur cluster assembly and known to bind Cu. This deubiquitination stabilizes ISCU, thereby preventing its proteasomal degradation. Rescue experiments further confirmed that ISCU is a key downstream effector mediating USP11's cuproptosis resistance effect. Finally, in patient-derived CRC organoid models, knockdown of USP11 significantly enhanced cuproptosis upon elesclomol/CuCl treatment, validating our in vitro findings. Collectively, our work identifies USP11 as a novel inhibitor of cuproptosis in CRC, acting through the stabilization of ISCU. This newly uncovered USP11-ISCU axis contributes to tumor resistance against cuproptotic stress and highlights a potential therapeutic target for sensitizing CRC to copper-induced cell death. - Source: PubMed
Publication date: 2026/05/08
Ke HailinZhang GuoweiLin WeiliJiang YuecuiWu MeinaZhang YueyiSong WeiyangWang FuhaiYan Songling - Chronic kidney disease is a worldwide health problem, and its incidence is on the rise. It has previously been shown that ubiquitin-specific protease 11 (USP11) promotes partial epithelial-to-mesenchymal transition in uric acid-stimulated tubular epithelial cells during renal fibrosis. However, its specific function and mechanism in renal interstitial fibroblasts is still unknown. In this study, we found that uric acid could also upregulate the USP11 levels in cultured fibroblasts (NRK-49F) under dose gradient and time gradient, with an approximately 3-4 fold increase. Genetic and pharmacological depletion of USP11 blocked activation of renal interstitial fibroblasts leading to an approximately 70-90% reduction in α-SMA and collagen I expressions. USP11 increased the phosphorylation level of epidermal growth factor receptor, thereby activating its downstream signaling pathways, including phosphatidylinositol 3-kinase (PI3K)/protein kinase B and mitogen-activated protein kinase /extracellular regulated protein kinases, which further activated nuclear transcription factors, Snail and Slug. Moreover, USP11 could also affect the proliferation and migration of NRK49F, by upregulating the expression levels of proliferating cell nuclear antigen and cyclin E. Thus, our study offers comprehensive evidence that USP11 is a promising target for kidney fibrosis and that inhibiting USP11 could be an effective strategy for treating chronic kideny disease. - Source: PubMed
Publication date: 2026/05/06
Ma XiaoyanJiang DaofangLi XialinLi JinqingHu YanWang PeixinMo QingyiZhu JiayuZhang ShashaZhuang ShougangShi YingfengLiu Na - Major depressive disorder (MDD) is a highly disabling psychiatric condition characterized by profound synaptic dysfunction-particularly in the prefrontal cortex-which constitutes a core neuropathological hallmark of the disease. Nevertheless, the molecular mechanisms linking ubiquitination dynamics to stress-associated synaptic structural deficits remain poorly defined. In this study, we identified USP11, an X-linked deubiquitinating enzyme, as a key upstream regulator of the GSK3β/mTOR signaling cascade and the resultant synaptic structural impairments induced by chronic stress. In mice exposed to chronic unpredictable mild stress (CUMS), USP11 expression in the prefrontal cortex was markedly elevated, accompanied by aberrant phosphorylation of GSK3β and mTOR. Immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation analyses verified a specific interaction between USP11 and GSK3β. Subsequent biochemical and cellular assays demonstrated that USP11 directly deubiquitinates GSK3β, modulates its Ser9 phosphorylation level, and consequently alters its enzymatic activity. Functional investigations using transgenic mice and primary neuronal cultures revealed that USP11 acts as a negative regulator of synaptic integrity. Strikingly, USP11 deficiency conferred robust protection against stress-induced synaptic injury and behavioral impairments by restoring synaptic protein expression, preserving neuronal ultrastructure, and ameliorating depressive-like behaviors. Collectively, these findings delineate a critical USP11-GSK3β/mTOR-synaptic plasticity axis underlying depression-related neuropathology and underscore USP11 as a promising therapeutic target for synaptic preservation and neuroprotection in MDD. - Source: PubMed
Publication date: 2026/03/09
Li NingyuanFeng YuqiGong QianDuan HaoYan HanchunZhang HonghanWang ChaoLiu Zhongchun - Peroxiredogenase 2 (PRDX2) has been confirmed to be downregulated in patients with intervertebral disc degeneration (IDD). However, the role and mechanism of PRDX2 in the progression of IDD are still unclear. - Source: PubMed
Publication date: 2026/03/24
Kong FanguoLuan JiyaoPan QipengQiao YangWang Wenju