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
- Neurodevelopmental disorders are increasingly associated with immune phenotypes, including autoinflammation, immunodeficiency, and increased susceptibility to severe infection. To determine whether neurodevelopmental disorders-associated genes exert immune functions, we performed an arrayed siRNA screen targeting 28 genes with nonredundant cellular roles and assessed their effects on Zika virus (ZIKV) infection and innate immune pathways. We identified hits that intrinsically restrict ZIKV infection and modulate inflammatory pathways following infection. We further characterized the antiviral activity of the Hao-Fountain syndrome gene USP7, which potently restricts selected neurotropic orthoflaviviruses. USP7 inhibits ZIKV internalization before viral membrane fusion and genome release into the cytoplasm. Because USP7 plays a role in endosomal tubulation and recycling, we investigated whether endosomal recycling pathways restrict ZIKV infection. We identified the USP7-regulated E3 ubiquitin ligase TRIM27, as well as the recycling-associated Rab GTPases RAB11 and RAB35, as potent regulators of ZIKV infection. Infection assays using cell lines expressing pathogenic USP7 variants and primary fibroblasts from individuals with Hao-Fountain syndrome demonstrated that disease-associated USP7 mutations impair its antiviral activity and increase permissivity to ZIKV infection. These findings are consistent with recent case reports of severe viral infection during early life in individuals with Hao-Fountain syndrome. Collectively, our study identifies endosomal recycling pathways as important intrinsic restriction mechanisms against neurotropic orthoflaviviruses and nominates pathogenic USP7 variation as a candidate inborn error of immunity. - Source: PubMed
Publication date: 2026/09/10
Bonaventure BorisReyes KynaMartin Marie-FrancePan HengRichardson R BlakeBednarski EvaAshbrook Alison WSowa AllisonJanssen WilliamDanzinger OdedCupic AnastasijaMiorin LisaRice Charles MLim Jean KRosenberg Brad REvans Matthew JJohnson Jeffrey R - Radiotherapy is a fundamental modality in cancer treatment, used in the management of more than half of cancer patients. Beyond direct cytotoxicity, ionizing radiation activates innate immune pathways and inflammatory cytokines required for local tumor control and systemic (abscopal) responses. Yet in human tumors, DNA damage-induced immune activation is attenuated compared with the robust responses observed in mice, suggesting a human-biased checkpoint that constrains radioimmunity. Here, we identify a tumor-intrinsic, human-biased farnesoid X receptor (FXR)-tripartite motif containing 22 (TRIM22)-STAT1 proteostatic checkpoint that suppresses radiation-induced type I interferon signaling. Ionizing radiation stabilizes FXR, a nuclear receptor, through ubiquitin-specific peptidase 7 (USP7)-dependent deubiquitination, enabling FXR to transcriptionally induce the E3 ligase TRIM22. TRIM22 selectively binds STAT1 and catalyzes its K48-linked ubiquitination and degradation, extinguishing interferon-stimulated gene (ISG) programs downstream of cGAS-STING signaling. This regulatory circuit is absent in murine tumor cells, which lack a TRIM22 family member capable of destabilizing STAT1, providing a mechanistic explanation for the stronger radiation-induced immune responses observed in mice. Genetic disruption of FXR or TRIM22 preserves STAT1, amplifies type I interferon signaling, and enhances CD8⁺ T-cell activation and abscopal tumor control in peripheral blood mononuclear cell-humanized mice. Pharmacologic modulation of this pathway with ursodeoxycholic acid, a bile acid used clinically with reported FXR-antagonistic activity, suppresses radiation-induced TRIM22, restores STAT1-ISG signaling, and potentiates radiotherapy alone or with anti-PD-1 without overt toxicity in humanized models. Collectively, these findings define a human-biased checkpoint that limits radiotherapy-induced immunity and is absent in murine tumor cells, and highlight the FXR-TRIM22-STAT1 axis as an actionable target to enhance cancer radioimmunotherapy. - Source: PubMed
Publication date: 2026/09/30
Li XinyanJiang PeichengYin HuanHuo ZhenyuXu XinNowsheen SomairaAziz KhaledZheng SufeiSun NanChen BinLou ZhenkunDeng Min - Protein -sulfinylation is a reversible oxidative cysteine modification, but its contribution to acute liver injury such as those induced by acetaminophen (APAP) overdose has not been reported. Sulfiredoxin-1 (SRXN1) is the only oxidoreductase known to reduce the sulfinylated proteins, yet the substrates and mechanisms through which it protects against acute liver injury are unclear. Here, we show that hepatic protein -sulfinylation was markedly upregulated in APAP-overdose patients and mice. Hepatocyte-specific knockout or pharmacological inhibition of sensitized mice to APAP-induced acute liver injury. In contrast, overexpression of SRXN1, but not its oxidoreductase-dead C99S mutant, protected mice from APAP-induced liver injury. Mechanistically, we identified the deubiquitinase ubiquitin-specific protease 7 (USP7) as an SRXN1 substrate required for hepatoprotection. USP7 inhibition worsened APAP-induced liver injury, whereas its overexpression alleviated injury by stabilizing its deubiquitinase substrate heme oxygenase-1 (HO-1). Loss of SRXN1 enhanced -sulfinylation of USP7 at Cys315, promoting its ubiquitination and degradation. SRXN1 expression correlated with USP7 levels in human liver samples. Delayed lipid nanoparticle (LNP) delivery of SRXN1 messenger RNA (mRNA) mitigated established APAP-induced liver injury beyond the therapeutic window of -acetylcysteine. These findings define an SRXN1-USP7-HO-1 axis as a promising therapeutic target for oxidative liver injury and highlight LNP-mediated SRXN1 mRNA delivery as a potential treatment approach. - Source: PubMed
Publication date: 2026/09/29
Ke MengyunKim Jong-WonXu MeishuWang JingyuanLiu LingyiN P SyamprasadYang BinWang XiaofeiLi HuatianRen SongrongCarroll Kate SLi SongXie Wen - Ubiquitination is a crucial post-translational modification of proteins in eukaryotic cells. Deubiquitinating enzymes (DUBs) remove ubiquitin molecules from substrate proteins, thereby reversing ubiquitination and maintaining intracellular ubiquitin homeostasis. Dysregulation or dysfunction of DUBs is closely associated with various diseases. Among them, the ubiquitin-specific protease (USP) family, the largest subfamily of DUBs, plays a key regulatory role in tumor initiation and progression. This article systematically reviews the research progress on five representative USP family members closely linked to tumors, including USP7, USP22, USP10, USP35, and USP4, with a focus on their functional mechanisms in regulating major tumor-related signaling molecules and pathways, including p53, PTEN, c-Myc, and PD-L1. It also highlights their dual regulatory roles in tumor proliferation, resistance to apoptosis, metastasis, and immune evasion. Furthermore, this review summarizes the structural basis of USP catalysis and selectivity, the determinants of context-dependent USP functions, and the emerging roles of DUBs in tumor microenvironment remodeling and therapy resistance. We also discuss the latest advances in the development of selective inhibitors and new therapeutic modalities targeting these USPs, including PROTAC-mediated degradation, DUBTAC-mediated tumor suppressor stabilization, and molecular glue strategies. Although targeting DUBs for cancer therapy faces challenges such as substrate diversity, context-dependent functions, and functional redundancy within the family, it remains a promising strategy for tumor treatment. This review provides a theoretical foundation and research directions for further understanding the roles and mechanisms of the USP family in cancer and for developing targeted DUB-based anti-tumor therapies. - Source: PubMed
Publication date: 2026/09/10
Wang YananShi Jing - Precise and rapid control over cellular protein levels is essential to dissect complex biological systems. Chemical genetic approaches such as dTAG, in which a target is fused to a degron tag (FKBP12) and degraded upon small molecule-mediated recruitment of E3 ligases, have enabled rapid and tunable control over protein abundance. However, no analogous tool exists to precisely increase protein levels and actively reverse dTAG-mediated degradation. Here, we developed heterobifunctional small molecules (dubTAGs) that stabilize FKBP12-tagged proteins by recruiting endogenous deubiquitinases. Utilizing stem cell-derived cranial neural crest cells (CNCCs) in which the transcription factors SOX9 or TWIST1 are endogenously tagged with FKBP12, we identified OTUB1- or USP7-recruiting heterobifunctional molecules that demonstrated effective target stabilization and ternary complex formation. We demonstrate that dubTAG-mediated protein stabilization is dependent on deubiquitinase recruitment, target-specific, and can tunably and rapidly reverse dTAG-mediated degradation. We applied dubTAGs to assess how stabilizing endogenous SOX9 impacts chromatin accessibility in CNCCs, finding both monotonic and non-monotonic regulatory element responses that are driven by distinct sequence features. dubTAGs are readily applicable tools for investigating the effects of elevated protein levels and tunably reversing targeted degradation, enabling new approaches to study protein dosage effects in development, disease, and therapeutic discovery. - Source: PubMed
Publication date: 2026/09/18
Guharajan SunilSong XiangyangSengupta SachiWu QiongWei WenyiXiong YanJin JianNaqvi Sahin