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
- Inflammatory diseases impose a significant global healthcare burden, necessitating the development of effective anti-inflammatory agents. Many clinically used drugs are isolated from plants or derived from natural products via semi-synthetic procedures. Among natural products, coumarins have demonstrated broad-spectrum pharmacological activities. This study investigates the anti-inflammatory mechanisms of an uncommon natural coumarin, 7-methoxy-8-isopentenyloxycoumarin (7MI), isolated from the seed of the higher Mediterranean plant Magydaris pastinacea. 7MI's effects were assessed in LPS-stimulated Raw264.7 macrophages using immunoblotting, RT-qPCR, ChIP assay, chase assay, reporter assay, ELISA, phosphatase activity assay, and transfection. 7MI significantly reduced the release of pro-inflammatory cytokines, including IL-6 and MCP-1, and suppressed cyclooxygenase-2 (COX-2) expression. Mechanistically, 7MI attenuated canonical LPS-induced TLR4 signaling by inhibiting the parallel activation of the NF-κB and MAPK/AP-1 pathways. 7MI blocked NF-κB p65 nuclear translocation and its transcriptional activity. Concurrently, 7MI enhanced MAPK phosphatase-1 (MKP-1) activity, which deactivated p38MAPK, thereby dampening activation of AP-1 and the synergistic transcription factor CCAAT/enhancer-binding protein (C/EBP)β. Beyond transcriptional suppression, 7MI exerted a distinct post-translational effect by accelerating COX-2 proteasomal degradation through inhibition of the deubiquitinases USP7 and USP22, leading to enhanced K48-linked polyubiquitination of the COX-2 protein. Crucially, in vivo administration of 7MI dramatically improved survival rate and mitigated multi-organ damage in a murine model of fatal sepsis. These findings suggest that 7MI exerts broad-spectrum anti-inflammatory effects by simultaneously suppressing canonical TLR4-driven transcriptional cascades to halt de novo inflammatory mediator synthesis and by promoting pro-inflammatory protein clearance, highlighting its potential as a lead compound for LPS-associated inflammatory disorders. - Source: PubMed
Publication date: 2026/08/21
Huang Shiu-WenChen Hsiu-ChenLupia AntonioMeleddu RitaDistinto SimonaMaccioni EliasChuang Chin-HuiCottiglia FilippoHsu Ming-Jen - Myeloproliferative neoplasms (MPN) are shaped by epigenetic rewiring that extends beyond canonical JAK2V617F-driven signaling. This review argues that context-dependent chromatin states, not merely genetic lesions, determine disease trajectory, fibrotic transformation, and leukemic progression. We synthesize recent evidence indicating that PRC2 deficiency is supported by the strongest MPN-specific evidence for BRD4 dependency, whereas PARP/BCL-2 vulnerabilities associated with TET2/IDH mutations and USP7 dependency associated with ASXL1 remain supported primarily by related myeloid malignancies or preclinical studies. Introducing the concept of an "epigenetic clock" of clonal evolution, we propose that MPN cells acquire progressively pathological chromatin states that can be quantified through composite methylation and accessibility scores. Importantly, temporal synthetic lethality, using short epigenetic pulses to remodel chromatin before applying targeted agents, offers a rational scheduling strategy to expose non-redundant dependencies while sparing normal hematopoiesis. We outline a translational roadmap incorporating cfDNA methylome biomarkers, ongoing BET inhibitor trials, and emerging single-cell perturbation approaches. Finally, we highlight the "dark epigenome" of repetitive elements as an unexplored therapeutic frontier. Collectively, these findings suggest that context-restricted chromatin vulnerabilities may offer therapeutic opportunities for disease-modifying intervention in progression-prone MPN clones. - Source: PubMed
Abdelgawwad El-Sehrawy Amr Ali MohamedAl-Khreisat Mutaz JamalKubaev AzizRajapov AdilbekIsmael Sajida HusseinAlhasso BahjatKaur IrwanjotBainsal Neeraj - FLT3-ITD mutations in acute myeloid leukemias (AMLs) cause ligand-independent signaling. One way signaling pathways potently and immediately influence cell fates is by phosphorylating key fate-determining proteins to trigger their proteolysis. We investigated the master transcription factor (MTF) driver of granulo-monocytic lineage-fates, CEBPA, for regulation by this mechanism because we found high CEBPA mRNA but little CEBPA protein in versus -wildtype AML cells, and inhibiting FLT3-ITD signaling with tyrosine kinase inhibitors (TKI) rapidly rescued CEBPA protein. Mass spectrometry revealed that CEBPA interacts with major ubiquitin-proteasome pathway (UPP) components: the ubiquitin-ligase UHRF1 and the deubiquitinase USP7. TKI treatment decreased the phosphorylation of CEBPA (Ser21) and USP7 (Ser18) alongside shifts in CEBPA interactions from degradative UHRF1 to protective USP7, stabilizing CEBPA and activating differentiation. Similarly, TKIs and UPP inhibitors stabilized the USP7 client p53, triggering apoptosis specifically in FLT3-ITD cells. Notably, UPP inhibitors (such as bortezomib) successfully stabilized CEBPA and p53 even in TKI-resistant cells. Because FLT3-ITD signaling functionally suppresses CEBPA and p53, genetic mutations in or were mutually exclusive with FLT3-ITD in clinical series. In summary, FLT3-ITD drives the UPP-mediated destruction of CEBPA and p53, positioning UPP inhibitors as promising therapeutic candidates acting downstream of TKIs. - Source: PubMed
Publication date: 2026/07/30
Saunthararajah YogenGu XiaorongBiswas SudiptaZahran ZeinabBae SongaBalusu RameshJha BabalMaciejewski Jaroslaw - Neuroblastoma (NB) is a common pediatric malignancy in which activating mutations of anaplastic lymphoma kinase (ALK) drive tumor progression, yet the underlying mechanisms remain incompletely understood. Here, we demonstrate that ALK signaling promotes glycolysis and M2 macrophage polarization through the USP7-SOX9-MFAP2 axis. Using qRT-PCR, western blot, and co-culture systems, we found that ALK inhibition with lorlatinib reduces lactate production, downregulates M2 markers, and upregulates M1 markers in NB cells and NB mouse models. Mechanistically, Co-IP and ubiquitination assays revealed that ALK recruits and activates the deubiquitinase USP7, which deubiquitinates and stabilizes SOX9. Dual-luciferase reporter and ChIP-qPCR analyses further demonstrated that SOX9 directly binds to the MFAP2 promoter to activate its transcription. Functional assays showed that elevated MFAP2 enhances glycolysis, leading to increased lactate and immunosuppressive factor secretion, which in turn polarizes tumor-associated macrophages toward the pro-tumor M2 phenotype. Importantly, in vivo experiments confirmed that MFAP2 overexpression partially reverses the anti-tumor effects of lorlatinib. These findings identify the ALK/USP7/SOX9/MFAP2 cascade as a critical regulator of metabolic reprogramming and immune evasion in NB, and suggest that targeting this axis may represent a promising therapeutic strategy for high-risk NB. - Source: PubMed
Publication date: 2026/08/15
Lai CaiminXu KuntingLi RenfuChen JianxingZheng ZiyiZhong MinWang YangShen ZhiyongChen Feng - - Source: PubMed
Publication date: 2026/08/12
Ma Cong-CongJin Cheng-YunGuo Nin-JieLiu Hong-MinYin Qian-GeWang Yu-BingLiu Yu-FeiZhang YuWang NingLu Guo-LiangLi YanNan-Zhang Zheng Yi-Chao