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
- 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
Publication date: 2026/08/12
Edward AnnaPuttapaka Srinivas NVulli AravindKalivendi Shasi V - Various cellular stressors inhibit translation initiation and promote ribosome disassembly, thereby transiently inducing stress granules (SGs), dynamic ribonucleoprotein condensates that contain mRNAs and RNA-binding proteins. Although SG assembly is usually reversible, dysregulated SG dynamics can trigger the formation of persistent ubiquitin-positive protein inclusions. There is increasing evidence that this conversion of SGs into insoluble aggregates represents a central pathogenic mechanism in neurodegenerative proteinopathies, such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). TAR DNA-binding protein 43 (TDP-43) and Tau are causative factors in ALS and AD, respectively, and both localize to SGs under stress conditions. During disease progression, TDP-43 or Tau within SGs undergoes pathological changes that promote the formation of neurotoxic inclusions, which propagate neuronal dysfunction and death. This review summarizes recent advances in understanding the molecular factors that regulate SG assembly and disassembly, as well as the pathological processes that drive the conversion of SGs into aggregates associated with neurodegenerative diseases. Particular emphasis is placed on the role of the ubiquitin-specific protease 10 (USP10), which modulates SG dynamics and has been mechanistically implicated in both ALS and AD. Finally, we discuss the therapeutic potential of targeting these pathways to mitigate neurodegenerative disease progression. - Source: PubMed
Publication date: 2026/08/04
Takahashi MasahikoAbe TakayukiFujii Masahiro - Chronic exposure to ultraviolet A (UVA) radiation is the principal environmental driver of skin photoaging, yet the upstream molecular events that commit irradiated keratinocytes to senescence remain poorly understood. Here we show that SIRT6, an NAD-dependent protein deacetylase with established roles in genome maintenance and organismal longevity, functions as a central gatekeeper of keratinocyte homeostasis under photic stress. Using a chronic UVA irradiation model in mice together with cultured human keratinocytes, we demonstrate that UVA inflicts extensive DNA damage and G2/M cell-cycle arrest, accompanied by selective depletion of SIRT6 among all sirtuin family members. Mechanistically, UVA suppresses the deubiquitinase USP10 at both transcriptional and post-transcriptional levels, thereby licensing ubiquitin-dependent proteasomal degradation of SIRT6. The resulting SIRT6 deficiency unleashes hyperactivation of the DNA-damage sensor PARP1, amplifying genomic injury signaling and driving keratinocytes into irreversible senescence with concomitant elaboration of a broad pro-inflammatory secretory programme encompassing chemokines and cytokines. Pharmacological reactivation of SIRT6 with the selective agonist UBCS039 reverses epidermal hyperplasia, attenuates DNA damage and senescence marker accumulation, and suppresses inflammatory mediator induction both in vivo and in vitro, establishing SIRT6 loss as a causal rather than correlative event. Furthermore, molecular docking and functional validation identify osthole, a plant-derived coumarin from the medicinal herb Cnidium monnieri, as a candidate SIRT6-engaging compound that counteracts UVA-induced senescence and inflammation in keratinocytes. Collectively, these findings define a USP10-SIRT6-PARP1 signaling axis whose disruption underlies cutaneous photoaging and suggest that SIRT6-directed strategies may offer therapeutic benefit against UV-driven tissue degeneration. - Source: PubMed
Publication date: 2026/07/31
Zhang YuxiZuo XuleiHou XiaoyuZhang CongZhang Juan - Triple-negative breast cancer (TNBC) is an aggressive subtype lacking effective treatment options, and paclitaxel resistance remains a major clinical challenge. This study investigated the role of VASN in mediating paclitaxel resistance in TNBC by integrating transcriptomic and single-cell RNA sequencing data from public databases and clinical samples. Using paclitaxel-resistant TNBC cell lines (MDA-MB-231R and CAL-51R) and xenograft models, we revealed that VASN was significantly upregulated in resistant TNBC cells and tissues, correlating with poor prognosis. Mechanistically, CEBPB directly bound to the VASN promoter to activate its transcription, and VASN interacted with IGF2BP3 via its LRR domain, recruiting USP10 to deubiquitinate and stabilize IGF2BP3 by suppressing K48-linked polyubiquitination. Stabilized IGF2BP3 enhanced ABCB1 expression through mA-dependent mRNA stabilization, activating the PI3K/AKT pathway and driving paclitaxel resistance. Genetic or pharmacological inhibition of VASN resensitized resistant cells to paclitaxel, and computational drug screening identified Trametinib as a candidate to downregulate VASN. Trametinib synergized with paclitaxel to effectively suppress tumor growth without obvious toxicity in resistant models. In summary, we uncovered a new CEBPB-VASN/IGF2BP3/USP10-ABCB1 axis responsible for paclitaxel resistance in TNBC. Targeting VASN with Trametinib in combination with paclitaxel represents a promising therapeutic strategy to overcome chemoresistance, offering a rationale for precision medicine in resistant TNBC. - Source: PubMed
Publication date: 2026/07/13
Liu HaoLu ZexiuChen MaoshanLi ZhenghangChen JianYang XingyuWan XueyingTu GangLiu ManranTang Lingfeng