Ask about this productRelated genes to: OTUB1 antibody
- Gene:
- OTUB1 NIH gene
- Name:
- OTU deubiquitinase, ubiquitin aldehyde binding 1
- Previous symbol:
- -
- Synonyms:
- FLJ20113, FLJ40710
- Chromosome:
- 11q13.1
- Locus Type:
- gene with protein product
- Date approved:
- 2003-12-12
- Date modifiied:
- 2014-11-19
Related products to: OTUB1 antibody
Related articles to: OTUB1 antibody
- Ferroptosis is an iron-dependent form of regulated cell death driven by lethal lipid peroxidation and has emerged as a promising therapeutic vulnerability in cancer. Increasing evidence highlights its critical role in controlling tumor progression, overcoming therapeutic resistance, and enhancing antitumor immunity. Recent studies have identified the ubiquitin-proteasome system (UPS), particularly deubiquitinases (DUBs), as key regulatory nodes that determine ferroptotic susceptibility and represent attractive therapeutic targets. DUBs promote cancer cell survival and drug resistance by modulating the ubiquitination, stability, and functional activity of central ferroptosis regulators, thereby enabling tumor cells to evade oxidative stress and treatment-induced cytotoxicity. Several DUBs, such as OTUD5, OTUB1, USP7, USP14, USP22, and USP35, have been recognized as potent suppressors of ferroptosis that contribute to resistance against chemotherapy, radiotherapy, and targeted therapies. Importantly, pharmacological inhibitors or genetic silencing of these DUBs can reactivate ferroptotic cell death, resensitize resistant tumors to conventional and targeted therapies, and improve overall therapeutic outcomes. These findings position DUBs as highly actionable drug targets and support the development of DUB-directed inhibitors as ferroptosis-sensitizing agents in cancer treatment. Beyond regulating intrinsic tumor cell survival, DUB-mediated ferroptosis control also influences tumor-immune interactions and the tumor microenvironment, thereby affecting immune evasion and responsiveness to immunotherapy. This review comprehensively summarizes current progress in targeting DUB-mediated ferroptosis regulation, highlights emerging pharmacological strategies against UPS components, and discusses their translational potential for overcoming therapeutic resistance and improving cancer treatment efficacy. - Source: PubMed
Publication date: 2026/05/22
El-Sehrawy Amr Ali Mohamed AbdelgawwadMohammed Sumaya NadhimAbdulhadi Haitham LVora Manoj ABasunduwah Tina SaeedSingh GunjanArora VimalNayak Priya PriyadarshiniIqbal Muhammad ShahidMuslem Wessam T - Liver cancer is one of the most common malignant tumors worldwide. Pyroptosis, a novel form of programmed cell death, plays an important role in the occurrence and development of liver cancer. The deubiquitinase OTUB1 is associated with various types of programmed cell death, but its relationship with pyroptosis is unclear. To study the role and mechanism of OTUB1 in pyroptosis in liver cancer, we conducted this study. - Source: PubMed
Publication date: 2026/04/28
Chu Wen-QiXu Rui-LingLiu Ming-NaHu ChenGeng Xin-YuLiu JingLv ChengqianLi YanWang JingWang Xin-Hong - Hepatocellular carcinoma (HCC) treatment faces dual challenges: resistance to targeted therapy and low response rates to immunotherapy. These issues are rooted in the immunosuppressive tumor microenvironment (TME). Ferroptosis and autophagy, two critical cellular processes, play complex and paradoxical roles in HCC drug resistance and immunoregulation, and they interact closely. This review explores how the OTU deubiquitinase family, especially OTUB1, acts as a central hub coordinating the autophagy-ferroptosis balance. Additionally, other OTU family members, such as OTUD3, OTULIN, and OTUD6B, contribute to HCC progression by modulating similar pathways, highlighting the need for a broader therapeutic approach. Specifically, OTUD3 suppresses HIF-1α-driven angiogenesis, OTULIN inhibits NF-κB-mediated inflammation, and OTUD6B stabilizes pVHL to impede metastasis, collectively demonstrating their synergistic or antagonistic interactions with OTUB1 in reshaping the TME. This coordination drives HCC drug resistance and remodels the immune microenvironment. OTUB1 suppresses ferroptosis and maintains tumor cell survival by deubiquitinating and stabilizing key proteins like SLC7A11, GPX4, and p62. It also promotes immune escape by modulating PD-L1 stability and immune cell function. Consequently, therapeutic strategies targeting the OTU family-such as developing selective inhibitors for multiple members, using intelligent nanodelivery systems, and combining them with ferroptosis inducers or immune checkpoint inhibitors-show significant potential for reversing drug resistance and improving immunotherapy efficacy. Expanding these strategies to include other OTU members could enhance efficacy and reduce resistance. Addressing how the OTU family precisely modulates the intersection of autophagy and ferroptosis, and how it reshapes immune cell metabolism and function within the TME, is critical for developing novel combination therapies. This article provides a crucial theoretical foundation for developing novel combination strategies targeting metabolism-immune crosstalk. - Source: PubMed
Publication date: 2026/05/05
Zhao PengchengZhang Ping - Deubiquitinase-targeting chimera (DUBTAC) has recently emerged as a promising technology for inducing targeted protein stabilization (TPS). DUBTACs are heterobifunctional molecules that recruit deubiquitinases (DUBs) to induce deubiquitination and stabilization of target proteins. However, DUBTAC development has been hindered by the scarcity of DUB ligands. In this study, we report the discovery of novel covalent ligands of the OTUB1 DUB through structure-activity relationship (SAR) studies of the previously reported OTUB1 ligand EN523. Our lead compound (MS8572), which features a new heterocyclic core, covalently modified OTUB1 faster and more effectively, while also displaying enhanced stability and aqueous solubility compared to EN523. Furthermore, was selective for OTUB1 over several cysteine-containing proteins and did not inhibit the OTUB1 deubiquitinase activity. Lastly, by utilizing , we developed an effective CFTR DUBTAC. Overall, we developed new and improved OTUB1 covalent ligands, expanding the limited number of DUB ligands that can be harnessed for TPS. - Source: PubMed
Publication date: 2026/05/04
Song XiangyangWu QiongChen LiInuzuka HiroyukiZhong YueQi YihangLin YindanKabir MdXiong YanWei WenyiJin Jian - Restoring CD8⁺T cell infiltration and potentiating anti-tumor immune responses in the tumor microenvironment (TME) is critical for developing effective immunotherapies against triple-negative breast cancer(TNBC), while the regulatory role of N⁶-methyladenosine (m⁶A)-modified circular RNAs (circRNAs) in TNBC immune escape remains largely unelucidated. Whole-transcriptome microarray analysis combined with bioinformatics mining was conducted on TNBC tissues to screen circRNAs associated with immune evasion. RNA immunoprecipitation (RIP), RNA pulldown, and methylated RNA immunoprecipitation (MeRIP) assays were performed to verify the m⁶A modification of circFOXA1 and its interaction with gasdermin C (GSDMC). In vitro T cell-mediated tumor cytotoxicity assays and in vivo xenograft models in C57BL/6 mice were used to investigate the functional roles of the circFOXA1/GSDMC axis in TNBC anti-tumor immunity. Luciferase reporter and actinomycin D assays were further applied to clarify the regulatory mechanism of GSDMC on OTUB1 and programmed cell death-ligand 1 (PD-L1) expression. CircFOXA1 was identified as an m⁶A-modified circRNA with high stability and upregulation in TNBC, and its expression was significantly negatively correlated with CD8⁺T cell infiltration in TNBC tissues. Functionally, circFOXA1 induced immunosuppression in a CD8⁺T cell-dependent manner both in vitro and in vivo. Mechanistically, the m⁶A writer METTL14 mediated the m⁶A modification of circFOXA1, and the m⁶A reader YTHDF2 promoted circFOXA1 circularization. CircFOXA1 impaired immune cell-dependent tumor killing by upregulating GSDMC expression, which further enhanced OTUB1 mRNA stability at the post-transcriptional level. OTUB1-mediated deubiquitination subsequently stabilized PD-L1 protein, ultimately inhibiting CD8⁺T cell infiltration and driving TNBC immune escape. This study identifies a novel regulatory axis of m⁶A-modified circFOXA1/GSDMC/OTUB1/PD-L1 in mediating TNBC immune escape, where GSDMC enhances PD-L1 protein stability via OTUB1-dependent deubiquitination. These findings reveal a new molecular mechanism underlying TNBC immune evasion and identify circFOXA1 as a potential therapeutic target to improve the efficacy of anti-PD-1/PD-L1 immunotherapy in TNBC. - Source: PubMed
Publication date: 2026/04/22
Shen HonghongLi BoyuWen XiaoqianZhao ChangqingWang Chen