Proteins USP14 , Human
- Known as:
- Proteins USP14 , Human
- Catalog number:
- C191
- Product Quantity:
- 10μg
- Category:
- -
- Supplier:
- Novoprotein
- Gene target:
- Proteins USP14 Human
Related genes to: Proteins USP14 , Human
- Gene:
- USP14 NIH gene
- Name:
- ubiquitin specific peptidase 14
- Previous symbol:
- -
- Synonyms:
- TGT
- Chromosome:
- 18p11.32
- Locus Type:
- gene with protein product
- Date approved:
- 1999-02-01
- Date modifiied:
- 2016-02-23
Related products to: Proteins USP14 , Human
Related articles to: Proteins USP14 , Human
- Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by epidermal barrier dysfunction and persistent pruritus. However, the molecular mechanisms linking non-coding RNA regulation to ferroptosis and inflammatory signaling in AD remain poorly understood. - Source: PubMed
Publication date: 2026/08/24
Du YueJin ShanXu KexinBao YutingFeng MengLi LiYan GuanghaiZhu LianhuaLi Liangchang - The development of metastasis marks an aggressive stage of head and neck squamous cell carcinoma (HNSCC) and is closely linked to unfavorable survival outcomes. While metadherin (MTDH) drives tumorigenesis, metastasis, and chemoresistance in HNSCC, its dysregulation mechanisms remain unclear. Here, we identify USP14 as a specific deubiquitinase that stabilizes MTDH. USP14-dependent deubiquitination of MTDH activates NF-κB signaling, which drives epithelial-mesenchymal transition and supports cancer stem cells maintenance, ultimately strengthening HNSCC metastasis and chemoresistance. Mechanistically, we uncovered a competitive interaction: USP14 competes with the ubiquitin ligase FBXW7 for MTDH binding, preventing FBXW7-mediated degradation. Consequently, USP14 inhibition significantly mitigates aggressive phenotypes, an effect reversed by MTDH reintroduction. Clinical analysis confirms that MTDH and USP14 are overexpressed and positively correlated in metastatic HNSCC tissues. In conclusion, our study reveals a regulatory axis where USP14 competitively counteracts FBXW7 to stabilize MTDH, driving HNSCC progression. These findings provide preclinical evidence that targeting USP14 is a promising therapeutic strategy to overcome metastasis and chemoresistance in HNSCC. - Source: PubMed
Publication date: 2026/08/19
Wang XueyingZhou YangTan JiaqiZhang DiekuoLiu ChaoWang JunchengZhang XinZhu GangcaiLiu Yong - Innate immunity serves as the host's primary defense against viral infection. Aberrant immune activation can trigger tissue damage and autoinflammatory disorders, which requires precise negative regulation to sustain immune homeostasis. RIG-I is a vital pattern recognition receptor that governs antiviral innate immune responses, and its function is tightly controlled by post-translational modifications. Ubiquitination directly modulates RIG-I activity, yet the regulatory mechanism underlying RIG-I inactivation in teleost fish remains poorly understood. Ubiquitin specific peptidase 14 (USP14) is an important deubiquitinating enzyme that regulates proteasome function and eliminates intracellular toxic proteins. In this study, we systematically explored the regulatory role and molecular mechanism of zebrafish USP14 in RIG-I-mediated antiviral innate immunity. Our results demonstrated that spring viremia of carp virus (SVCV) stimulation markedly upregulated USP14 expression in zebrafish. USP14 overexpression decreased the phosphorylation levels of TBK1 and IRF3, thereby repressing type I interferon (IFN1) production. USP14 is primarily localized to mitochondria, and partially localized to the Golgi apparatus and the endoplasmic reticulum. In addition, protein interaction assays and molecular docking verified the direct binding between USP14 and RIG-I. Mechanistically, USP14 removes K63-linked and K29-linked ubiquitin chains from RIG-I, and this deubiquitination suppresses RIG-I-mediated immune activation. Functional validation showed that USP14 overexpression enhances SVCV replication and induces cell death. Conversely, USP14 knockdown or treatment with its specific inhibitor IU1 abolishes these pro-viral effects. In conclusion, zebrafish USP14 functions as a deubiquitinase that interacts with RIG-I and removes its K63-linked ubiquitination. This modification inhibits RIG-I-dependent IFN signaling, impairs host antiviral immunity, and consequently promotes SVCV proliferation. - Source: PubMed
Publication date: 2026/08/17
Zhang HongyingHu JihuanWu ChuxinYin ZijiaXu XiaowenHu ChengyuLi DongmingJiang Zeyin - Cerebral ischemia-reperfusion injury (CIRI) is a complex pathological process characterized by metabolic dysfunction, oxidative stress, neuroinflammation, and structural and functional alterations of the neurovascular unit (NVU). Across different studies, CIRI has been reported to be associated, to varying degrees, with neuronal injury and neurological dysfunction. Increasing evidence suggests that exosomes (EXOs) derived from glial cells, particularly microglia and astrocytes, play critical roles in mediating intercellular communication and regulating injury progression in CIRI. This review systematically summarizes the context-dependent and heterogeneous functions of glia-derived EXOs in CIRI. Microglia-derived EXOs exhibit diverse and context-dependent functions depending on the activation state of donor cells and the surrounding microenvironmental conditions. Under pro-inflammatory conditions, EXOs released from microglia may exacerbate inflammation by carrying cargo components such as circular RNAs (circRNAs) and pro-inflammatory proteins, whereas EXOs associated with reparative states may support tissue recovery through the delivery of functional non-coding RNAs. These cargo components may participate in pathological regulation through multiple signaling pathways. Among them, the nuclear receptor coactivator 4 (NCOA4) axis is associated with ferroptosis, ubiquitin-specific protease 14 (USP14) with proteostasis/apoptosis, and thioredoxin-interacting protein (TXNIP) with inflammasome activity, all of which have been linked to reduced neuronal injury and functional recovery. In addition, M2-type-derived EXOs may participate in the regulation of synaptic plasticity and axonal regeneration by modulating the plexin A2 (PLXNA2)/RhoA/ROCK2 signaling pathway. Astrocyte-derived EXOs (ATC-EXOs) further contribute to NVU regulation. A2-type-derived EXOs have been reported in multiple experimental models to be associated with reduced NLR family pyrin domain containing 3 (NLRP3) inflammasome activity and alterations in the PI3K/Akt and MAPK signaling pathways, accompanied by attenuated inflammatory responses and improved blood-brain barrier (BBB) integrity in these models. Some studies suggest that these effects may be related to the transition of microglial phenotypes toward reparative states; however, sufficient in vivo mechanistic evidence supporting their direct regulatory effects remains lacking. In contrast, neurotoxic astrocytes (A1)-derived EXOs exhibit limited or context-dependent effects. Importantly, exosome function is highly state-dependent and cannot be fully explained by simplified pro-inflammatory microglia anti-inflammatory microglia (M1/M2) or A1/A2 paradigms. Moreover, extracellular vesicle heterogeneity and methodological limitations remain major challenges. Despite promising therapeutic potential, including the ability to cross the BBB and enable multi-target regulation, significant barriers to clinical translation persist, such as delivery efficiency, biodistribution, and standardization. Overall, glia-derived EXOs represent a dynamic and multi-level regulatory system in CIRI and a promising platform for precision therapeutic strategies. - Source: PubMed
Publication date: 2026/08/04
Yang ZhengyuhanChen HuilinZhang ZhenwangWei XiaomingHan WantingPeng TieZhu DanLiu Chao - Despite intensive multimodal therapy, high-risk neuroblastoma remains associated with poor clinical outcomes because of treatment resistance, recurrence, and progressive disease, underscoring the need for new therapeutic strategies. We investigated whether proteasome-associated deubiquitinating enzymes are therapeutically relevant in neuroblastoma by assessing ubiquitin C-terminal hydrolase L5 (UCHL5) and ubiquitin-specific protease 14 (USP14) expression in neuroblastoma tissues and evaluating the antitumor activity of VLX1570 in preclinical models. Immunohistochemical (IHC) analysis showed stronger UCHL5 and USP14 immunoreactivity in neuroblastoma tissues than in normal peripheral nerve tissue. In human neuroblastoma cell lines IMR-32, SK-N-SH, and SH-SY5Y, VLX1570 reduced cell viability in a dose- and time-dependent manner, induced apoptosis, and triggered G2/M arrest. These effects were accompanied by induction of CCAAT/enhancer-binding protein homologous protein (CHOP) and suppression of proliferating cell nuclear antigen (PCNA)-associated proliferative signaling, as reflected by reduced expression of PCNA, phospho-histone H3, and Bcl-2 together with increased p21 and p53 expression. PCNA knockdown experiments further supported inhibition of PCNA-associated proliferative signaling as a functionally relevant component of VLX1570-induced cytotoxicity. In addition, VLX1570 enhanced cisplatin-induced apoptosis and potentiated cisplatin antitumor activity in neuroblastoma xenograft models. Together, these findings support proteasome-associated deubiquitinating enzyme inhibition as a pharmacologic strategy in neuroblastoma and provide a rationale for further evaluation of VLX1570, particularly in combination with cisplatin. - Source: PubMed
Publication date: 2026/07/15
Yang Wei-HsunKhoi Chong-SunKuo Kuan-LinChow Po-MingHsu Chen-HsunKao Yi-JuLin Wei-ChouChang Shang-JenLiao Shih-MingTai FeliciaShi Chung-ShengLiu Shing-HwaChang Pey-JiumWang Chung-ChengHuang Kuo-How