Ask about this productRelated genes to: OTUD6A Blocking Peptide
- Gene:
- OTUD6A NIH gene
- Name:
- OTU deubiquitinase 6A
- Previous symbol:
- -
- Synonyms:
- FLJ25831, HSHIN6, DUBA2
- Chromosome:
- Xq13.1
- Locus Type:
- gene with protein product
- Date approved:
- 2005-09-28
- Date modifiied:
- 2015-09-03
Related products to: OTUD6A Blocking Peptide
Related articles to: OTUD6A Blocking Peptide
- PR domain zinc finger protein 1 (PRDM1) functions as a critical transcriptional repressor. The role of PRDM1 in various tumors is controversial, and its specific mechanism in bladder cancer (BCa) remains unclear. In the present study, we demonstrated that PRDM1 expression is downregulated in both human BCa tissues and BBN-induced mouse models of BCa. Gain- and loss-of-function experiments revealed that PRDM1 delays cell cycle progression, suppresses BCa cell proliferation, and enhances chemosensitivity, whereas PRDM1 knockdown promotes cell proliferation and induces chemoresistance. Ovarian tumor deubiquitinase 6 A (OTUD6A) is a deubiquitinating enzyme that prevents the proteasomal degradation of CDC6. PRDM1 directly binds to the OTUD6A promoter and suppresses its transcription, thereby reducing CDC6 deubiquitination and promoting its degradation. Knockdown of CDC6 or OTUD6A abrogates the protective effects of PRDM1 both in vitro and in vivo. Consistently, PRDM1 expression is negatively correlated with CDC6 and OTUD6A expression in BCa tissues. Collectively, these findings demonstrate that PRDM1 acts as a tumor suppressor in BCa by inhibiting OTUD6A transcription and promoting CDC6 degradation. We propose a PRDM1‒OTUD6A‒CDC6 axis model, providing novel insights into PRDM1 as a potential therapeutic target in BCa. - Source: PubMed
Publication date: 2026/02/23
Cui JianfengChen ShouzhenLiu XiaochenJiang XuewenCheng GuangzhouLiu ZhifengZhao HuiZhu YaofengShi BenkangZou Yongxin - Parkinson's disease (PD) is a severe neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons. Emerging evidence suggests that deubiquitinating enzymes (DUBs), which regulate protein homeostasis through the cleavage of ubiquitin chains, play critical roles in PD pathogenesis. In this study, we discovered that a DUB, ovarian tumor deubiquitinase 6A (OTUD6A), was significantly upregulated in both PD patients and PD mouse models. Notably, OTUD6A deficiency effectively protected dopaminergic neurons from degeneration and improved motor deficits in both acute and chronic PD mouse models. Through comprehensive mass spectrometry analysis and co-immunoprecipitation assays, we identified that actin gamma 1 (ACTG1) serves as a key substrate of OTUD6A. Mechanistically, OTUD6A specifically interacts with the 8-181 aa domain of ACTG1 and preferentially cleaves K48-linked polyubiquitin chains, thereby enhancing ACTG1 protein stability in neuronal cells. The stabilized ACTG1 subsequently binds to p53 and facilitates its nuclear translocation, leading to the transcriptional activation of pro-apoptotic genes and promoting neuronal apoptosis. Collectively, our findings demonstrate that OTUD6A promotes dopaminergic neuron degeneration and PD progression by deubiquitinating and stabilizing ACTG1, which in turn activates a p53-dependent apoptotic pathway. These findings identify OTUD6A as a potential therapeutic target for PD intervention. - Source: PubMed
Publication date: 2025/12/03
Zhao XiaChen FanXiong LiXu XiaoxiaMeng ZiyaoDeng YuAi QiLi LuyaoYu QinChen LinjieWang RuyaRen YiyuZheng WenhuaWei JuruiYu HoumingLiang Guang - Asthma is a prevalent chronic airway disorder characterized by airway hyperresponsiveness (AHR), persistent airway inflammation, and airway remodeling. Emerging evidence implicates ubiquitination-a critical post-translational modification-in asthma pathogenesis. The study identifies ovarian tumor deubiquitinase 6A (OTUD6A), a deubiquitinase with established oncogenic roles, as a novel regulator of airway inflammation and remodeling. The study finds a significantly upregulation of OTUD6A in asthma patients and murine lungs, with predominant localization in airway epithelial cells. Genetic ablation of Otud6a prevents house dust mite (HDM)-induced AHR, airway inflammation, mucin hypersecretion in both chronic and acute asthma models, as well as airway remodeling in chronic asthma model. Mechanistically, multi-omics analysis identifies the secreted cytokine human (h)Resistin/mouse resistin-like molecule α (mRELMα) as a substrate of OTUD6A. OTUD6A deubiquitinates and stabilizes hResistin by specifically removing its K48-linked polyubiquitin chains at lysines K2 and K19 via the catalytic residue C152, thereby blocking its proteasomal degradation and promoting its secretion. The consequent accumulation of hResistin potentiates epithelial alarms production and facilitates epithelial-mesenchymal transition, driving airway inflammation and airway remodeling. Furthermore, adeno-associated virus 6-mediated OTUD6A silencing in murine lungs markedly ameliorates asthma phenotypes. These findings establish a pathogenic OTUD6A-hResistin/mRELMα axis and nominating OTUD6A as a promising therapeutic target for asthma intervention. - Source: PubMed
Publication date: 2026/01/20
Pan WeitingXi XinruDai WeiXiao TingfangChen YeqingChen XuanyuGe XiangtingZhao ChengguangZhang HuiZhang YaliZhang Weixi - Ubiquitination regulates various physiological and pathological processes. However, the impact of atypical AKT ubiquitination and its potential role in tumorigenesis remain unclear. Here we show that AKT is modified by K27-linked ubiquitination by the E3 ubiquitin ligase TRIM21, a process antagonized by the deubiquitinase OTUD6A. As such, TRIM21 acts as a tumor suppressor by repressing AKT activity, whereas OTUD6A counteracts AKT suppression. Mechanistically, TRIM21-mediated AKT ubiquitination disrupts SKP2-mediated or TRAF6-mediated K63 ubiquitination, thereby blocking AKT membrane localization and its kinase activity. Upon activation in response to amino acids, S6K1 directly phosphorylates and inactivates OTUD6A, enabling a negative feedback loop regulating AKT activity in a deubiquitination-dependent manner. In agreement with this model, Otud6a deficiency reduces lung tumorigenesis in a Kras-driven lung cancer mouse model and TRIM21 induction alleviates hyperactive AKT-induced tumor growth in vivo. Thus, our findings unveil a fine-tuned regulation of AKT through atypical ubiquitination and suggest the strategy for combating AKT-driven cancers by targeting the TRIM21-OTUD6A axis. - Source: PubMed
Publication date: 2025/11/04
Jiang QiweiSong PeipeiZhang ShuishenRen QinZhu MeiyanGe JiaweiBu LangChen WeiWu XuejiHan ShiyaoSu YaqingWang LeiXie WeiCheng ChaoPeng ZhenweiGuo Jianping - Cattleyak is a hybrid between cattle and yak; the underlying mechanism for its spermatogenic arrest is still unclear, and it's a typical male sterile mammal. In this work, we cloned the OTUD6A gene of cattleyak and analyzed it by bioinformatics. The expression level of OTUD6A in testicular tissues and undifferentiated spermatogonia of cattleyak was significantly lower than that in yak (p < 0.05). Overexpression of OTUD6A in cattleyak promoted the viability and proliferation activity of cattleyak undifferentiated spermatogonia (p < 0.05). Furthermore, OTUD6A overexpression resulted in significant upregulation of genes associated with proliferation (p < 0.05). Therefore, the aberrant expression of OTUD6A in undifferentiated spermatogonia of cattleyak impaired its proliferation and decreased its growth potentiality, thereby affecting the development of undifferentiated spermatogonia. This study provided a new theoretical basis for further elucidation of the molecular mechanism of spermatogenesis arrest in cattleyak. - Source: PubMed
Dong WenjingZhang PengShen ZhenhuaGuo ShujunXiong XianrongLi JianCai Xin