Ask about this productRelated genes to: USP14 antibody
- 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: USP14 antibody
Related articles to: USP14 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 - Androgen receptor splice variant 7 (AR-V7) is a principal driver of resistance to androgen receptor signaling inhibitors in castration-resistant prostate cancer. By virtue of its truncated ligand-binding domain, AR-V7 functions as a constitutively active transcription factor, sustaining oncogenic signaling independently of androgenic ligands. Its biogenesis is orchestrated by epigenetic regulators and splicing factors, including jumonji domain-containing 6 and eukaryotic translation initiation factor 4A3, which facilitate the production of stabilizing peptides such as that encoded by circSRCAP. AR-V7 establishes a distinct transcriptional programme, frequently cooperating with full-length AR and co-activators like YAP1/TAZ to activate proliferative genes (e.g., UBE2C) and repress tumor suppressors (e.g., SLC22A3). Protein stability is tightly controlled by deubiquitinases USP22 and USP14, while targeted degradation is mediated by the HSP70-STUB1 complex. Clinically, detection of AR-V7 in circulating tumor cells serves as an actionable biomarker, enabling selection of taxane chemotherapy over ineffective androgen receptor signaling inhibitors. Emerging therapeutic strategies include proteolysis-targeting chimaeras, N-terminal domain inhibitors, and agents targeting CDK9 or PRMT1. Overcoming AR-V7-mediated resistance will require deeper biological dissection using single-cell multi-omics and the development of rational combination therapies, representing a pivotal challenge in precision oncology for castration-resistant prostate cancer. - Source: PubMed
Publication date: 2026/05/11
Li JunWang XiongTang Xiaoshuang - Abnormal expression of adenosine A2B receptor (ADORA2B) may be involved in the development of osteoarthritis (OA). Therefore, it is necessary to explore its role and mechanism in OA progression to understand OA pathogenesis. - Source: PubMed
Li ZhiZhang PengOuyang ChuanweiShen ZhouGuo Genwei - Therapeutic resistance to chemotherapy or radiotherapy is a significant issue in several cancers, including head and neck squamous cell carcinoma (HNSCC). One pathway associated with therapeutic resistance is the NFκB pathway, which promotes survival in response to the cytokine TNFα, a key mediator of chemotherapy and radiotherapy-induced cytotoxicity. However, direct targeting of the NFκB pathway is associated with significant toxicity and thus targeting the regulation of this pathway is a promising therapeutic target. We recently demonstrated that the USP14/UCHL5 inhibitor b-AP15 inhibits NFκB activity, inhibiting proliferation and inducing apoptosis in HNSCC cells. Furthermore, b-AP15 treatment sensitised HNSCC cells to the cytotoxic effects of TNFα, as well as TNF-inducing radiation treatment. Here, we investigated if b-AP15 sensitised HNSCC cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a cancer selective member of the TNF family. b-AP15 treatment sensitised HNSCC cells to TRAIL treatment. Mechanistically, we show that b-AP15 induced expression of the TRAIL receptor Death Receptor 5 (DR5)/TRAIL Receptor 2 (TRAILR2), which was required for b-AP15-mediated TRAIL sensitisation. b-AP15 induced reactive oxygen species (ROS) and activated the JNK signalling pathway and both ROS and JNK signalling were required for the induction of DR5 expression and TRAIL sensitisation. We further show that b-AP15-mediated reduction of the NFκB-dependent gene XIAP induced DR5 expression and TRAIL sensitisation and that combination between b-AP15 and IAP antagonists was synergistic in HNSCC cells in vitro. Our data further define the mechanism of b-AP15-mediated cytotoxicity and highlight potential combination treatments that warrant further exploration in pre-clinical studies in HNSCC. - Source: PubMed
Publication date: 2026/05/02
Brown Fin T AQuesne LucyWootton Louisa MFoxell HollyErseven IpekEwen Benns EmiliaTate MollyMorgan Ethan L - Combining immunotherapy with other treatments improves survival in colorectal cancer (CRC), yet some patients remain unresponsive. Tumor-associated macrophages (TAMs) are a key immune cell population driving this immunotherapy resistance and fostering an immunosuppressive microenvironment. To overcome this, we screened a deubiquitinating enzyme (DUB) library targeting TAMs and identified USP14 as specifically upregulated in TAMs. Inhibiting USP14 reversed their pro-tumor functions, promoted M1 polarization, enhanced tumor cell killing, and activated effector T cells. USP14 inhibition also increased PD-L1 expression on tumor cells, alleviating T cell suppression. , combining a USP14 inhibitor with an anti-PD-1 antibody synergistically enhanced immunotherapy efficacy, suppressed tumor progression, and improved survival in a mouse colon cancer model. Thus, USP14 is a promising target to overcome immunotherapy resistance in CRC. - Source: PubMed
Publication date: 2026/03/13
Xiao DanFang JunJian HuiYu Yang