Ask about this productRelated genes to: USP7 antibody
- Gene:
- USP7 NIH gene
- Name:
- ubiquitin specific peptidase 7
- Previous symbol:
- HAUSP
- Synonyms:
- -
- Chromosome:
- 16p13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1998-10-12
- Date modifiied:
- 2017-01-04
Related products to: USP7 antibody
Related articles to: USP7 antibody
- The deubiquitinase USP7 is a critical regulator of tumorigenesis, known for stabilizing the MDM2-p53 pathway. Emerging evidence highlights USP7's p53-independent roles in proliferation and tumorigenesis. Our study reveals that USP7 is broadly upregulated in breast cancer, including triple-negative breast cancer (TNBC), a subtype characterized by near-universal TP53 loss. This provides a model to investigate p53-independent functions of USP7. Using TNBC models, we define p53-independent roles of USP7 in regulating proteostasis and tumorigenesis. Importantly, genetic and pharmacologic USP7 inactivation impaired tumor progression in TNBC models. To explore USP7's role in p53-mutant TNBCs, we performed deep quantitative proteomics across TNBC cell lines, identifying shared USP7 targets involved in cell proliferation, genome stability, and proteostasis. Acute USP7 inactivation allowed us to infer proximally controlled proteins that are likely direct targets. Surprisingly, many of the proteins downregulated by USP7 inhibition are E3 ubiquitin ligases. Thus, a key USP7 function in TNBC is to antagonize the degradation of ubiquitinating enzymes, since these enzymes are often susceptible to auto-ubiquitination and degradation. Notably, we identified TOPORS, a dual ubiquitin- and SUMO-ligase, among novel USP7 substrates. TOPORS interacts with the BRCA1-A DNA damage repair complex, suggesting a USP7-TOPORS-BRCA1-A axis that might further explain the continued proliferation of genomically unstable TNBCs. Collectively, these data nominate USP7 as a potential therapeutic vulnerability in TNBC. - Source: PubMed
Publication date: 2026/05/23
Kim AhhyunGopalakrishnan PriyaSuárez-Pizarro MarinaChen Claire CWang XianxiMcCoy Sydney MUmesh NikitaMordant AngieBarker Natalie KHerring Laura EKakati Rasha TSpanheimer Philip MEmanuele Michael JBenavente Claudia A - Ferroptosis is an iron-dependent form of regulated cell death driven by lethal lipid peroxidation and has emerged as a promising therapeutic vulnerability in cancer. Increasing evidence highlights its critical role in controlling tumor progression, overcoming therapeutic resistance, and enhancing antitumor immunity. Recent studies have identified the ubiquitin-proteasome system (UPS), particularly deubiquitinases (DUBs), as key regulatory nodes that determine ferroptotic susceptibility and represent attractive therapeutic targets. DUBs promote cancer cell survival and drug resistance by modulating the ubiquitination, stability, and functional activity of central ferroptosis regulators, thereby enabling tumor cells to evade oxidative stress and treatment-induced cytotoxicity. Several DUBs, such as OTUD5, OTUB1, USP7, USP14, USP22, and USP35, have been recognized as potent suppressors of ferroptosis that contribute to resistance against chemotherapy, radiotherapy, and targeted therapies. Importantly, pharmacological inhibitors or genetic silencing of these DUBs can reactivate ferroptotic cell death, resensitize resistant tumors to conventional and targeted therapies, and improve overall therapeutic outcomes. These findings position DUBs as highly actionable drug targets and support the development of DUB-directed inhibitors as ferroptosis-sensitizing agents in cancer treatment. Beyond regulating intrinsic tumor cell survival, DUB-mediated ferroptosis control also influences tumor-immune interactions and the tumor microenvironment, thereby affecting immune evasion and responsiveness to immunotherapy. This review comprehensively summarizes current progress in targeting DUB-mediated ferroptosis regulation, highlights emerging pharmacological strategies against UPS components, and discusses their translational potential for overcoming therapeutic resistance and improving cancer treatment efficacy. - Source: PubMed
Publication date: 2026/05/22
El-Sehrawy Amr Ali Mohamed AbdelgawwadMohammed Sumaya NadhimAbdulhadi Haitham LVora Manoj ABasunduwah Tina SaeedSingh GunjanArora VimalNayak Priya PriyadarshiniIqbal Muhammad ShahidMuslem Wessam T - The tumor suppressor p53 is a pivotal guardian against tumorigenesis, with its activity primarily constrained by the ubiquitin E3 ligase Mdm2. However, the full complexity of the Mdm2-p53 regulatory network remains elusive. Here we report that the deubiquitinating enzyme USP21 physically interacts with and stabilizes Mdm2 in a deubiquitinase activity-independent manner. Mechanistically, USP21 acts as a scaffold to facilitate the USP7-Mdm2 interaction, enhancing Mdm2 stability and consequently promoting p53 ubiquitination and degradation. Functionally, USP21-mediated p53 suppression attenuates its tumor suppressive activity and accelerates colorectal cancer progression. Clinically, USP21 is upregulated in colorectal cancer tissues, and its elevated expression correlates with poor overall survival in patients with wild-type p53 tumors, but not in those with p53 mutations. These findings establish USP21 as an important regulator of the Mdm2-p53 axis and reveal its critical role in promoting colorectal carcinogenesis via p53 inhibition. - Source: PubMed
Publication date: 2026/05/22
Wang ZhongyuYao BoHe WeiranGuo XiaoruiYu NingTang SuyunLuo LinzhuWang FangZhao KailiangMei Yide - Glioblastoma (GBM) remains a highly lethal malignancy for which current treatments offer only a limited therapeutic benefit. Although vimentin (VIM) is classically regarded as a cytoskeletal protein, its role in tumour immune regulation is poorly understood. Here, we showed that extracellular tumour-derived VIM was associated with impaired CD8 T-cell antitumour immunity and altered metabolic fitness. Single-cell RNA sequencing revealed that CD8 T cells within VIM-high tumour microenvironments exhibited dysfunctional transcription in GBM. Functional assays revealed that VIM knockdown (VIM-KD) increased the antitumour activity of CD8 T cells. Notably, under in vitro monoculture conditions, the modulation of VIM expression did not induce significant changes in GBM cell proliferation or apoptosis, indicating that VIM did not exert direct cytotoxic or growth-promoting effects on tumour cells. In contrast, in vivo tumour growth was strongly correlated with VIM expression levels, which was subsequently demonstrated to be mediated by CD8 T-cell-dependent immune suppression. Metabolic analyses indicated that exposure to VIM-overexpressing (VIM-OE) tumour cells correlated with reduced triglyceride levels and decreased mitochondrial oxidative phosphorylation in CD8 T cells. In vivo, VIM-KD mice exhibited decreased intracranial tumour growth and prolonged survival. Mechanistically, VIM stability is subject to posttranslational regulation, and we identified the deubiquitinase USP7 as a key regulator associated with maintaining VIM protein levels by limiting its proteasomal degradation. Collectively, these findings reveal a previously unrecognized USP7-VIM axis that mediates metabolic dysfunction and immune suppression in GBM, providing a mechanistic foundation for future therapeutic investigations. - Source: PubMed
Publication date: 2026/05/19
Tang LiyanWang HaoChen JinmingZhang YangHuang YulunLi Xuetao - Renal fibrosis is a pathological feature of advanced-stage diabetic kidney disease (DKD). Here, we investigated the effect of Pirfenidone (PFD) on renal fibrosis under diabetic conditions and its molecular mechanism. Sirius red staining and immunohistochemistry were used for histological analysis in rat kidney. Levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were detected by kits. Lipid hydroperoxide, malondialdehyde (MDA), glutathione peroxidase (GPX), and superoxide dismutase (SOD) were measured by commercial kits. Immunofluorescence staining was used to evaluate the expression and colocalization of USP7 and DNMT1. Mitochondrial and cytoplasmic reactive oxygen species (ROS) levels were detected. GLIS1, DNMT1, and USP7 mRNA were measured by RT-qPCR. Protein levels of DNMT1, USP7, fibronectin, p-Smad2, Smad2, p-Smad3, and Smad3 were detected by Western blot. Methylation of the GLIS1 promoter was assessed utilizing methylation-specific polymerase chain reaction (MSP). Chromatin immunoprecipitation (ChIP) and co-immunoprecipitation (Co-IP) verified molecular interactions. PFD alleviated renal injury and fibrosis in DKD rats by suppressing TGF-β1/Smad signaling. PFD attenuated renal oxidative stress and mitochondrial dysfunction in DKD rats. GLIS1 knockdown reversed PFD's protective effects in high glucose (HG)-exposed HK-2 cells, abolishing its improvements in oxidative stress, mitochondrial function, and fibrosis. PFD attenuated HG-induced GLIS1 promoter hypermethylation by suppressing DNMT1 binding and activity, thereby restoring GLIS1 expression. PFD suppressed DNMT1 activity by disrupting USP7/DNMT1 complex. Importantly, the USP7/DNMT1 axis mediated the regulatory effect on GLIS1, which subsequently counteracted PFD's protective effects on HG-stimulated HK-2 cells. PFD upregulates GLIS1 by disrupting the USP7/DNMT1 complex, which subsequently suppresses the ROS/TGF-β1/Smad pathway to alleviate renal fibrosis in DKD. This study identifies the USP7/DNMT1/GLIS1 epigenetic axis as a critical upstream mechanism driving the protective effects of PFD, providing new therapeutic targets for DKD treatment. - Source: PubMed
Tu WeiHu LeiWu LitingZhou HongtaoYang RongChen Yanxia