Ask about this productRelated genes to: KEAP1 Blocking Peptide
- Gene:
- KEAP1 NIH gene
- Name:
- kelch like ECH associated protein 1
- Previous symbol:
- -
- Synonyms:
- KIAA0132, MGC10630, MGC1114, MGC20887, MGC4407, MGC9454, INrf2, KLHL19
- Chromosome:
- 19p13.2
- Locus Type:
- gene with protein product
- Date approved:
- 2003-09-30
- Date modifiied:
- 2015-11-23
Related products to: KEAP1 Blocking Peptide
Related articles to: KEAP1 Blocking Peptide
- Biomolecular condensates in the cytoplasm and nucleus contribute to carcinogenesis through aberrant signaling by assorted transcription factors and fusion oncoproteins. Oral cancer, which is highly prevalent worldwide, frequently occurs in a U-shaped "high-risk" zone (floor of mouth, side of tongue, and anterior fauces) which forms the path of liquid transit through the mouth. We previously reported that environmental stresses of saliva-like hypotonicity and beverage-like temperature changes triggered cycles of disassembly/reassembly of biomolecular condensates of GFP-tagged human myxovirus resistance protein (MxA; alias Mx1) in oral cancer cells. In the present study, we identified some of the constituents of GFP-MxA cytoplasmic condensates in oral cells. These condensates were isolated from interferon (IFN)-λ1-treated GFP-MxA expressing OECM1 human oral cancer cells using magnetic bead-based immunoisolation. Unbiased peptide identification confirmed the presence of MxA/Mx1 peptides; however, the strongest intensity was for the BACH1 transcription factor family. Immunofluorescence analyses confirmed the association of BACH1 and the family member Nrf2 with cytoplasmic human GFP-MxA condensates. Moreover, GFP-BACH1 and GFP-Nrf2 colocalized with cytoplasmic human HA-MxA condensates in transiently transfected OECM1 cells. Western blot assays confirmed the presence of BACH1 and Nrf2 proteins in complexes isolated using anti-MxA pAb. As much as BACH1 and Nrf2 regulate oxidative stress response genes, it was remarkable that immunofluorescence assays revealed the presence of heme oxygenase 1 (HO1)-a downstream redox regulator-in GFP-MxA condensates. However, these condensates were devoid of p62, KEAP1 and Cul3. In terms of aberrant function, in live cells, the Nrf2 transcription factor underwent rapid disassembly and reassembly cycles driven by saliva-like hypotonicity, and was also disassembled by sulforaphane. The data highlight the unexpected intersections in oral cells between MxA condensates and BACH1, Nrf2 and HO1-proteins well known to be involved in pathways regulating cellular responses to environmental and oxidative stresses, antiviral defense, oral epithelial dysplasia, and cancer progression and metastases. - Source: PubMed
Publication date: 2026/05/26
Sehgal Pravin BYuan Huijuan - This research aimed to examine the clinical relevance and biological function of the tight junction protein claudin-2 (CLDN2) in gastric cancer, along with its regulatory interactions with lymphoid enhancer-binding factor 1 (LEF1) and the Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway. Analysis of CLDN2 expression and its prognostic implications in gastric cancer was conducted using data from the Cancer Genome Atlas (TCGA) database. The effects of CLDN2 or LEF1 on gastric cancer (GC) cells were detected by RT-qPCR, Western blot, cell-counting kit-8 (CCK-8), transwell assay, flow cytometry, CO-IP and immunofluorescence assays. The interactions between CLDN2 and LEF1 was predicted and validated using Gene MANIA and GEPIA. The functional association between CLDN2 and LEF1 was analyzed by rescue experiments. In GC tissues, CLDN2 was significantly upregulated and correlated with tumor stage, lymph node metastasis, and poor prognosis, showing elevated levels in young patients (21-40 years old) and individuals infected with Helicobater pylori (H. pylori). CLDN2 silencing inhibited GC cell proliferation, migration and invasion, induced G1-phase cycle block and apoptosis, and decreased cyclin D1 expression. CLDN2 and LEF1 were positively correlated and directly interacted, and suppressing LEF1 hindered the progression of GC. CLDN2 reduced KEAP1 expression and promoted NRF2 protein stability through post-transcriptional regulation. Silencing CLDN2 or LEF1 activated the KEAP1/NRF2 pathway and inhibited downstream p65, IkappaB kinase (IKK) and IκB protein expression. Reducing LEF1 levels counteracted the effects of CLDN2 on GC cell growth and KEAP1/NRF2 pathway. Increased levels of CLDN2, which modulate the LEF1 and KEAP1/NRF2 pathways, are correlated with GC progression and may be used as a marker for poor prognosis. - Source: PubMed
Publication date: 2026/06/10
Yao JZhang Y HLing Y XShi X - The bioactive constituents of ginger ( Roscoe) display well-documented immunomodulatory and antimicrobial effects; however, the role of these components in combating dengue virus (DENV) and other flaviviruses infection remains unknown. Here, activity-guided molecular networking and antiviral screening identified 10-shogaol as the primary antiviral phytochemical in ginger, with a half-maximal inhibitory concentration (IC) value of 2.502 μM. Mechanistically, 10-shogaol bound the -octyl-β-d-glucopyranoside (β-OG) pocket of viral envelope protein (E), interfering with viral attachment and conferring broad antiviral properties against DENV and Zika virus (ZIKV). Additionally, 10-shogaol suppressed proinflammatory cytokines and mitigated tissue damage in mice by acting as a novel Nrf2 activator by inhibiting Keap1-mediated ubiquitination and proteasome degradation. Activation of Nrf2 by 10-shogaol induced antioxidant gene expression and inhibited inflammatory NF-κB signaling. Collectively, our study suggests that 10-shogaol acts as a broad-spectrum entry inhibitor against DENV and ZIKV as well as confers anti-inflammatory benefits for mitigating virus-induced inflammatory tissue damage. - Source: PubMed
Publication date: 2026/06/10
Li MengxueZhou RenyuGuo LeiLiu YifengLu DaiqiangChen HaoXu WeiPeng JiaojiaoWu WenjiaoYu JianhaiHe LiangliangGao FengZhang Qiao - Novel antioxidant peptides from silver carp bone collagen (SCBC) and their antioxidation mechanism were unlocked by integrating HPLC-MS/MS-based label-free peptidomics, bioinformatics-aided structure-function analysis, and cytoprotective validation against oxidative damage. Results showed that the ultrafiltrated ≤1 kDa fraction contributed the highest in vitro antioxidant activities to SCBC hydrolysates by α-chymotrypsin and ficin, from which 349 peptides were identified through peptidomics. Nine antioxidant peptide candidates with high abundances were further selected by computer-aided screening and bioinformatic characterization, among which GSRGETGPAGR, GRVGPSGPAGAR, and AGEPGLVGAR exhibited both good DPPH•-scavenging (IC = 775.37, 977.54, and 59.10 μM, respectively) and Fe-chelating (IC = 47.22, 91.51, and 767.01 μM, respectively) capacities with IC < 1 mM. The quantum chemical analysis suggested that peptide linkage acylamino or N-terminal amino groups were their redox-active sites. Moreover, the molecular docking analysis revealed that they may majorly form strong hydrogen bonds with core Arg415 within the Kelch domain of Keap1, thereby potentially disrupting the Keap1-Nrf2 interaction and activating the Keap1-Nrf2-ARE pathway. Consequently, the production of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase was facilitated, leading to the degradation of reactive oxygen species and reduction of malondialdehyde content, which significantly enhanced the viability of HepG2 cells against HO-induced oxidative damage. These findings offered insights into the high-value utilization of fish by-product bones and multi-dimensional mechanisms for food-derived antioxidant peptides. - Source: PubMed
Publication date: 2026/05/27
Zhang JinLin FengMei YimengXie RuoyuChen JiaxinHu JunDu HongyingHao GuijieLi ShuangxiChen Wenxuan - Psoriasis is a chronic autoimmune inflammatory dermatosis with a global prevalence exceeding 3%. Available therapeutic approaches for psoriasis, encompassing topical formulations, monoclonal antibodies, and phototherapy, seldom elicit full clinical remission in practice, yet are plagued by exorbitant costs or impractical administration protocols. To enhance the therapeutic efficacy of ferulic acid (FA), a widely used naturally occurring antioxidant, a series of short-chain fatty acids (SCFAs) were selected for the structural modification of FA, thereby endowing the covalent conjugate with enhanced antioxidant activity, as well as potent immunomodulatory and cell cycle regulatory properties. Using an imiquimod (IMQ)-induced psoriasis-like mouse model, pentanoylated ferulic acid methyl ester (PentFAMe) was identified as the most potent candidate compound, exhibiting the highest efficacy. Its therapeutic effects and underlying mechanism were further elucidated through in vivo and in vitro approaches. Compared with the parent compounds, the conjugate PentFAMe exhibits superior and more comprehensive pharmacological activity. The activity of PentFAMe is substantially higher than the individual component likely to be formed in vivo upon hydrolysis. Pentanoic acid alone displays potent anti-proliferative and anti-inflammatory activities via suppression of HDAC3/6 expression. PentFAMe exerts superior effects by inhibiting HDAC3/6 expression, thereby restoring acetylation levels of H3K27 and NF-κB p65. Meanwhile, PentFAMe surpassed ferulic acid in its ability to activate the antioxidant Nrf2 pathway. Furthermore, effective Nrf2 activation inhibited NF-κB phosphorylation, resulting in a notable decrease in proinflammatory cytokine and chemokine expression. PentFAMe, as a component in an oral formulation, is both cost-effective and convenient, offering a novel potential lead compound against psoriasis. - Source: PubMed
Publication date: 2026/06/10
Li ChenxiYang YuanyuanZhang AoHan HangLi XiandengZhang GuojiangChu LongXu BiaoZhang XiaoZhao Qinjian