Ask about this productRelated genes to: OTUB2 antibody
- Gene:
- OTUB2 NIH gene
- Name:
- OTU deubiquitinase, ubiquitin aldehyde binding 2
- Previous symbol:
- C14orf137
- Synonyms:
- FLJ21916, MGC3102
- Chromosome:
- 14q32.12
- Locus Type:
- gene with protein product
- Date approved:
- 2003-01-28
- Date modifiied:
- 2015-01-28
Related products to: OTUB2 antibody
Related articles to: OTUB2 antibody
- The ubiquitin-proteasome system (UPS) plays a central role in antiviral defense but is also frequently hijacked by viruses to facilitate their replication. Here, we demonstrate that the host deubiquitinase OTUB2 stabilizes the viral replication factor NSP8 of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through a dual-track mechanism. OTUB2 directly removes polyubiquitin chains from NSP8 to prevent its degradation. In parallel, OTUB2 stabilizes the viral papain-like protease (PLpro), which further promotes NSP8 stability through deubiquitination. Together, these effects preserve the functional integrity of the viral replication-transcription complex. Mechanistically, OTUB2-mediated stabilization of NSP8 potentiates NSP8-dependent suppression of type I interferon signaling, thereby promoting viral replication and immune evasion. Importantly, inhibition of OTUB2 disrupts OTUB2-mediated stabilization of NSP8 and PLpro, resulting in a marked reduction in viral replication and disease severity in cell culture systems and a hamster infection model. Collectively, our findings reveal a previously unrecognized mechanism by which SARS-CoV-2 utilizes the host deubiquitination system to stabilize its replication machinery and identify OTUB2 as a potential target for host-directed antiviral intervention. - Source: PubMed
Publication date: 2026/07/27
Gao WenyingWang HongfeiXin JingguoGu ChenjiaQiu LuZhang XueWang ChunleiZhang QingxiangLi ShuaiLi GuangquanZhang Wenyan - Argininosuccinate synthetase 1 (ASS1) is a rate-limiting enzyme in arginine biosynthesis, and its stability is regulated by TRAF2-mediated ubiquitination. Here, we report OTUB2 as a major deubiquitinase to stabilize ASS1, resulting increased arginine biosynthesis in colorectal cancer (CRC) cells; OTUB2 expression is elevated in CRC tissue, and patients with high OTUB2 expression exhibit shorter overall survival. As such, ectopic expression of OTUB2 promotes growth of CRC cells and xenograted tumors and accelerates cell migration and lung metastasis. Moreover, arginine deprivation induces marked expression of OTUB2 in CRC cells; mechanistically, arginine deprivation can activate AMPK, which in turn phosphorylates DDIT3, resulting its disassociation from C/EBPα and subsequent translocation into the cytoplasm and leading to increased binding of C/EBPα to the proximal promoter region of OTUB2 gene. Together, these data uncover a signaling pathway constituted of AMPK- DDIT3-C/EBPα-OTUB2-ASS1 to sense arginine deficiency and stimulate a metabolic compensatory pathway to sustain arginine homeostasis in CRC cells. - Source: PubMed
Publication date: 2026/07/10
Li MengyingZhang JieZhang HuiChen XiaolinZou XiuqunWang JiaminHuang WenyanPeng HaixiaJia HaoHou Zhaoyuan - This study aimed to clarify how cancer-associated fibroblast-derived exosomal circ_0067557 (CAF-exo circ_0067557) promotes epithelial-mesenchymal transition (EMT) in colorectal cancer (CRC) through BHLHE40-mediated transcriptional activation of OTUB2. - Source: PubMed
Publication date: 2026/05/11
Zhang DaoxuZhang JiaqiYang ChengWang YanWang MuhongYu Zhiwei - Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. Ferroptosis, an iron-dependent form of programmed cell death, has emerged as a potential therapeutic target. However, the regulatory mechanisms that allow CRC cells to evade ferroptosis are not fully understood. This study focuses on OTUB2, a deubiquitinating enzyme, and its role in stabilizing U2AF2, which allows CRC cells to resist ferroptosis and autophagy. We analyzed CRC cells and clinical samples to evaluate the effects of OTUB2 on U2AF2 deubiquitination. OTUB2 knockdown and overexpression models were established in CRC cell lines (LoVo, RKO, SW480, HT115) to assess ferroptosis and autophagy activity. Various assays, including western blotting, immunoprecipitation, colony formation, and transwell migration assays, were used to evaluate cell proliferation, migration, and iron metabolism markers. In vivo xenograft models were also employed to assess tumor growth under OTUB2-U2AF2 axis disruption. OTUB2 was highly expressed in CRC tissues compared to normal controls. Knockdown of OTUB2 significantly increased ferroptosis, while enhancing autophagy. Conversely, OTUB2 overexpression reduced ferroptosis and autophagy, maintaining CRC cell survival and proliferation. In vivo studies confirmed that disrupting the OTUB2-U2AF2 axis impaired tumor growth by activating both ferroptosis and autophagy. Importantly, a reciprocal activation relationship between ferroptosis and autophagy was observed under OTUB2-U2AF2 axis deficiency. OTUB2 stabilizes U2AF2 in CRC cells, enabling them to evade ferroptosis and autophagy. Disruption of the OTUB2-U2AF2 axis activates both processes, suppressing tumor growth. Targeting this axis presents a promising therapeutic strategy for CRC treatment. - Source: PubMed
Publication date: 2026/05/07
Chen XiQi YanxinNie QigangZhou KaiMo Ao - Docetaxel (DTX) is a standard chemotherapy agent for castration-resistant prostate cancer (CRPC); however, DTX resistance remains a major clinical challenge, and the underlying molecular mechanisms are not fully understood. In our study, it was found that OTUB2 was highly expressed in DTX-resistant CRPC and could be served as a key driver of DTX resistance. Mechanistically, OTUB2 stabilizes the m5C reader ALYREF by removing its K48-linked polyubiquitin chains, leading to increased ALYREF protein levels. And then, ALYREF enhances the mRNA stability and expression of ABCG4, thereby promoting ATP-dependent efflux of DTX. Moreover, the expression of OTUB2 mRNA and protein could be regulated by FOXD3-AS1 derived from cancer-associated fibroblasts (CAFs). More importantly, treatment with OTUB2 inhibitor (OTUB2-IN-1) resensitized resistant CRPC to DTX. Together, our findings establish OTUB2 as a novel driver of DTX resistance in CRPC and highlight the role of CAFs-derived FOXD3-AS1 and OTUB2/ALYREF/ABCG4 axis in modulating DTX resistance of CRPC. - Source: PubMed
Publication date: 2026/03/17
Ke Zhi-BinChen Jia-YinLin BinChen Chao-RanXue Yu-TingSun Jiang-BoYan Zi-HengZhao Yu-XuanLiu Meng-XinWang ZhenXue Xue-YiZheng Qing-ShuiWei YongXu Ning