Ask about this productRelated genes to: USP28 antibody
- Gene:
- USP28 NIH gene
- Name:
- ubiquitin specific peptidase 28
- Previous symbol:
- -
- Synonyms:
- KIAA1515
- Chromosome:
- 11q23.2
- Locus Type:
- gene with protein product
- Date approved:
- 2000-05-26
- Date modifiied:
- 2016-10-05
Related products to: USP28 antibody
Related articles to: USP28 antibody
- USP25 and USP28 are critical deubiquitylases (DUBs) that have been implicated in various diseases, particularly cancer and cardiac dysfunction. Several small-molecule inhibitors have been reported, exhibiting dual inhibitory activity in the low micromolar range. In this study, we present a strategy that merges structural features of the previously identified inhibitors AZ1 and vismodegib to develop a new class of potent dual inhibitors. Several of these newly synthesized compounds exhibit high potency across multiple orthogonal assays and demonstrate excellent selectivity over other ubiquitin-specific proteases. Moreover, a suitable negative control has also been identified, supporting the validity of the observed effects in cellular assays. These results highlight the potential of these compounds to serve as advanced chemical probes for dual USP25/USP28 inhibition and as candidates for further therapeutic development. - Source: PubMed
Publication date: 2026/04/22
Hernandez-Olmos VictorPatzke Jonathan VincentStone Caroline ENair Radhika KaralWeller KathrinSauer FlorianEndres ErikJamai OumaimaRachor LeaWarmutz Cornelia HSchwalm Martin PMitrovic MarkoGrenier VincentEhrler Johanna H MProschak AnnaHeering JanSotriffer ChristophMulder Monique P CKnapp StefanKisker CarolineProschak Ewgenij - Mitosis is monitored by and mechanically coupled to the spindle assembly checkpoint (SAC), which halts mitotic progression until fidelity is met, disregarding time efficiency. Conversely, there exists SAC-independent, efficiency-promoting surveillance mechanically uncoupled from mitosis. This external mitotic surveillance (EMS), comprising 53BP1, USP28, and p53, induces post-mitotic arrest following prolonged, inefficient mitosis. To explore additional EMS inputs, we performed comparative CRISPR-Cas9 screens for genes functionally safeguarded by EMS, identifying, among others, two components of the RZZ kinetochore complex-KNTC1 and ZWILCH. Depleting KNTC1, which impairs fidelity-ensuring activities of mitosis, including SAC, triggered population-level post-mitotic arrests without widespread, characteristic mitotic delay or catastrophe. Instead, KNTC1 depletion produced mostly viable mitosis and yet activated EMS via ectopic accumulation of 53BP1-USP28-p53 complexes over normal mitotic duration. These results suggest that when the fidelity-ensuring control within mitosis is itself compromised, mitosis is rendered invalid from without by EMS, echoing Gödel's incompleteness theorems. - Source: PubMed
Publication date: 2026/03/17
Shulman AvitalOzaki KanakoChang Lukas RHoong EdenBryan Tsou Meng-Fu - Gossypol is a polyphenolic compound recognized for its role as a Bcl-2 family protein inhibitor, attracting considerable interest mainly due to its antitumor properties. However, its development as a therapeutic agent has faced hurdles from off-target side effects, partially stemming from an incomplete understanding of its target profile. In this study, we identified Gossypol as a multi-deubiquitinating enzyme (DUB) inhibitor, exhibiting preference for the ubiquitin-specific protease (USP) subfamily members. Gossypol demonstrated IC values ranging from 0.30 μM to 4.97 μM against USP2 CD, USP7 CD, USP8 CD, USP28 CD and USP9X CD. Mechanistic studies, including 1D NMR, IC shift assays, fluorescence quenching experiments, and enzymatic reversibility tests revealed that Gossypol mainly acts as non-covalent inhibitor against multiple DUBs, with binding affinities towards representative USPs between 10 and 30 μM. Cell-based assays confirmed Gossypol's efficacy in inhibiting intracellular DUB activity, leading to increased ubiquitination levels. Moreover, Gossypol exhibited cytotoxic effects on human breast, prostate, and colorectal cancer cell lines, at least partially through downregulating the oncogenic substrates of targeted DUBs such as c-Myc, Mcl-1, MDM2, and Cyclin D1. Collectively, our findings position Gossypol as a promising small-molecule inhibitor targeting DUBs, especially USPs, and provide a rationale for further exploring its therapeutic potential in USP-driven cancers. - Source: PubMed
Publication date: 2026/03/15
Gui LinChen ChunyingGao JingZhu MengyingXu ZhuoZhou HuZhang NaixiaShi Li - Esophageal squamous cell carcinoma (ESCC) remains a lethal malignancy with limited therapeutic options. The deubiquitinase USP28 has emerged as a key stabilizer of the oncogenic transcription factor ΔNp63 in squamous cancers, yet its functional significance and therapeutic potential in ESCC are unexplored. Here, we elucidate that USP28 is essential for ESCC proliferation. Genetic ablation of USP28 induced profound G2/M cell cycle arrest and apoptosis, phenotypes mechanistically linked to the destabilization of ΔNp63. We further establish that USP28 directly binds to and deubiquitinates ΔNp63, thereby controlling its protein stability. Crucially, targeting this axis with CT1113, a novel and potent USP28 inhibitor, recapitulated the anti-tumor effects of genetic knockdown, triggering ΔNp63 degradation, cell cycle arrest, and apoptosis in ESCC cells. Importantly, CT1113 administration significantly suppressed tumor growth in ESCC xenograft models. Our study not only defines the USP28/ΔNp63 axis as a critical driver of ESCC but also validates the therapeutic strategy of pharmacologically inhibiting USP28 for the treatment of this aggressive cancer. - Source: PubMed
Publication date: 2026/03/13
Cai ChangzhouCheng NuoLuo HangqiGuan HuiyuanPeng JinZhang PuminChen XiaoliFang Yanfei - Parkinson's disease (PD) is a neurodegenerative disorder characterized by neuroinflammation and the aggregation of α-synuclein (α-syn), which lead to progressive neuronal loss, yet regulatory mechanisms remain elusive. Zinc finger and BTB domain-containing protein 16 (ZBTB16) has been implicated as a critical nexus integrating proteostatic dysregulation with neuroimmune axis activation in neuropathogenesis. However, its specific role and molecular mechanisms in PD remain poorly understood. Building upon the initial RNA sequencing analysis showing ZBTB16 upregulation in peripheral blood mononuclear cells (PBMCs) of PD patients, we further analyzed its expression in PBMCs from 57 PD patients and postmortem striatal tissues, revealing significant upregulation relative to controls. In rotenone (ROT)-induced PD models, elevated ZBTB16 correlated with increased apoptotic activity. Mechanistic investigations in SH-SY5Y dopaminergic neurons and BV2 microglia-like cells (BV2 cells) showed that ZBTB16 overexpression enhanced α-syn expression through transcriptional activation and post-translational modifications, promoting aggregation independent of mutation status. Confocal microscopy confirmed α-syn/SUMO1 colocalization in PD striatal tissues, with microglial models demonstrating ZBTB16-dependent UBC9 upregulation that increased SUMO1+/α-syn+ cells; knockdown reversed this effect. Additionally, in BV2 cells co-expressing mutant LRRK2 and α-syn, ZBTB16 amplified pathogenicity by boosting NLRP3 inflammasome activation, Gasdermin D (GSDMD) expression, and IL-1β/IL-18 secretion, with significant GSDMD/α-syn co-localization in PD tissues. Based on initial RNA sequencing analysis indicating that lnc-USP28-6 regulates ZBTB16 expression, systematic analysis of the ZBTB16 promoter identified lnc-USP28-6. Clinical data identified elevated lnc-USP28-6 in PD peripheral blood, which transcriptionally upregulated ZBTB16 and α-syn in SH-SY5Y cells independently of ROT. These findings unveil a novel lnc-USP28-6/ZBTB16 axis driving PD pathogenesis via dual mechanisms: exacerbating neuroinflammation through inflammasome activation and promoting α-syn aggregation via SUMOylation, indicating promising therapeutic targets. - Source: PubMed
Publication date: 2026/03/01
Wang NanWang ManYou YifeiAn JiajiaJia RuiZhao BinCao ZhangWang XianzhiGe RuliLi ChenWang Hongcai