Ask about this productRelated genes to: JOSD2 antibody
- Gene:
- JOSD2 NIH gene
- Name:
- Josephin domain containing 2
- Previous symbol:
- -
- Synonyms:
- SBBI54
- Chromosome:
- 19q13.33
- Locus Type:
- gene with protein product
- Date approved:
- 2005-11-10
- Date modifiied:
- 2014-11-19
Related products to: JOSD2 antibody
Related articles to: JOSD2 antibody
- Ubiquitination, a central post-translational mechanism, shapes the amplitude and duration of cellular signalling. Josephin domain-containing 2 (JOSD2), a Machado-Joseph disease (MJD) family deubiquitinase, eliminates ubiquitin moieties from ubiquitin-conjugated substrates and tunes proteostasis and signalling outputs. Emerging evidence links aberrant JOSD2 activity to diverse pathological states. - Source: PubMed
Publication date: 2026/04/30
Li ZefenHu JialiWang LingLiu YanTeng JiahuiWei ShufeiWang Liangliang - Atrial fibrillation (AF) is the most common sustained arrhythmia, and its initiation and progression involve multiple mechanisms, including electrical remodeling, structural remodeling, inflammatory responses, and oxidative stress. In recent years, the ubiquitin-proteasome system (UPS), a central pathway for maintaining intracellular protein homeostasis, has attracted increasing attention in the pathogenesis of AF. By regulating the degradation and expression of ion channel proteins, Ca-handling molecules, and pro-fibrotic signaling factors, the UPS plays a pivotal role in key pathological processes such as electrical and structural remodeling. Several E3 ubiquitin ligases (e.g., NEDD4-1/2, MuRF1, WWP1/2, TRAF6), deubiquitinating enzymes (e.g., JOSD2), and immunoproteasome subunits (e.g., β5i) have been shown to exert critical regulatory effects on atrial electrophysiological disturbances, interstitial remodeling, and inflammation. This review provides a comprehensive summary of the regulatory mechanisms of the UPS in AF-associated pathological processes, outlines potential therapeutic targets, and highlights current intervention strategies, including proteasome inhibitors, selective E3 ligase modulators, and natural compounds. Moreover, we discuss the latest advances and future perspectives regarding the application of UPS-based interventions in AF, aiming to provide theoretical foundations and research insights for the mechanistic exploration and innovative therapeutic development of AF. - Source: PubMed
Publication date: 2025/12/29
Huang RunzePu ZhipengChen Zhangrong - Hypertensive renal disease (HRD) is a significant driver of end-stage renal disease. Discovering novel therapeutic targets for HRD is essential for its prevention and treatment. Deubiquitinating enzymes (DUBs) have shown increasing significance in renal diseases. Here, we investigated the role and mechanism of the DUB, Josephin domain-containing protein 2 (JOSD2), in HRD. HRD was induced in wild-type or Josd2 knockout mice via a 4-week chronic infusion of angiotensin II (Ang II). We found that deficiency of JOSD2 aggravated renal injury, epithelial-mesenchymal transition (EMT), and fibrosis in HRD mice. Single-cell RNA-seq analysis indicated that JOSD2 is mainly expressed in tubular epithelial cells (TECs) of proximal tubules. Notably, the specific overexpression of JOSD2 in renal TECs alleviated the detrimental effects in Ang II-induced HRD mice. Mechanistically, through mass spectrometry combined with co-immunoprecipitation analysis, we considered protein kinase B (AKT) as a potential substrate of JOSD2. JOSD2 deubiquitinated the K63-linked ubiquitin chain of AKT via its active site H125 and then enhanced p62-mediated autophagic degradation of AKT. This process reduced the AKT level in TECs, thereby ultimately reducing renal EMT and fibrosis. Our study elucidates the role of the JOSD2-AKT axis in HRD and suggests that JOSD2 may serve as a promising therapeutic target for HRD. - Source: PubMed
Publication date: 2025/12/16
Fan ShijieZhao YingLi LuyaoZhao QingqingFang ZimingXu DiyunShao JingjingZhao YunjieLiang GuangHe XuelinZhu HongWang Yi - Colorectal cancer (CRC) remains a formidable clinical challenge, many patients exhibit limited responses to conventional chemotherapy and targeted therapies. Although immunotherapy has demonstrated potential, its efficacy is largely restricted to a subset of patients with high microsatellite instability (MSI-H), highlighting the critical need to identify key molecular drivers of immune evasion in CRC. Through comprehensive bioinformatic analysis, we identified the deubiquitinating enzyme JOSD2 as a key player in CRC progression, with elevated expression correlating with poor prognosis in MSI-H patients (HR = 4.79, 95% CI: 3.6-7.96) and dysregulation of multiple immune-related pathways. Mechanistically, we discovered that JOSD2 suppresses cGAS enzymatic activity by removing K27-linked ubiquitination, thereby promoting M2 polarization of macrophages, a process critical for immunosuppression in the tumor microenvironment. Furthermore, using the JOSD2 catalytic inhibitor HY041004, we demonstrated both and that the inhibition of JOSD2 activated the cGAS-STING signaling pathway, leading to robust anti-tumor effects in CRC. These findings not only uncover a novel immunomodulatory mechanism in colorectal cancer but also provide a therapeutic rationale for the development of JOSD2-targeted anticancer strategies. - Source: PubMed
Publication date: 2025/12/05
Du JiaminFan YiqunFu JunweiGe FujingZhu HongdaoYang ShuyuDai JingyuYuan TaoHe QiaojunYang BoZhu HongDong Xin - Glioblastoma Multiforme(GBM) is the most common primary malignant tumor of the central nervous system and the most prevalent primary malignant brain tumor in adults, accounting for over 50% of adult malignant primary brain tumors. Adult patients with GBM have a median age at onset ranging from 45.5 to 56 years, with no significant gender difference, and the 5-year survival rate is only 5%-10%. Despite the advancements in surgery and chemoradiotherapy, prognosis remains poor. There is an urgent need to identify novel therapeutic targets and prognostic biomarkers for GBM. Ubiquitin-specific protease 30 (USP30), a member of the deubiquitinating enzyme family, has been implicated in tumor progression. This study investigates the potential mechanisms of USP30 in GBM using proteomic analysis and functional validation. It further explores USP30's potential as a prognostic marker and therapeutic target in GBM, focusing on its downregulation and possible role in tumor suppression. - Source: PubMed
Publication date: 2026/11/05
Wu ChaoYang YanfeiChang XiaotingShang Wei