Ask about this productRelated genes to: KEAP1 antibody
- 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 antibody
Related articles to: KEAP1 antibody
- Mechanical and structural cues of the extracellular matrix (ECM) regulate tumor cell metabolism and drug response, yet the molecular mediators that link these biophysical signals are unclear. We present an elastically supported surface platform bioengineered with varying stiffness and collagen fiber anisotropy to replicate the fibrotic and mechanically inhomogeneous liver cancer microenvironment. Using this system, we identify Kelch-like ECH-associated protein 1 (KEAP1) as a mechanoresponsive mediator linking ECM stiffness to mitochondrial dynamics, redox adaptation, and chemoresistance in hepatocellular carcinoma (HCC). In substrate stiffness increase, biphasic KEAP1 expression, time-dependent mitochondrial remodeling via a KEAP1-BCL-2-DRP1 cascade, suppression of reactive oxygen species, and activation of antioxidant and glycolytic transcriptional programs were triggered. RNA sequencing revealed stiffness-dependent repression of mitochondrial fission genes and induction of AGE-RAGE signaling. At a functional level, cells grown in stiffer matrix demonstrated augmented proliferation and chemoresistance to cisplatin and sorafenib with nuclear translocation of NRF2. Multiplex imaging of human HCC tissues confirmed that collagen-rich regions co-localize with high KEAP1 and TOM20 expression, confirming the in vitro findings. This study demonstrates ECM stiffness to be a bioactive material property that guides mitochondrial and redox networks through KEAP1 signaling, and the mechanically tunable collagen platforms to be of a utility for dissection and manipulation of tumor adaptation mechanisms. - Source: PubMed
Publication date: 2026/05/12
Elblová PetraCalé AliciaAndělová HanaMorán LauraDe Bonis AdrianaHionides AlejandroNevzorova Yulia AKubovciak JanJirsa MilanKvětoň MartinStraník JaroslavLunova MariiaCubero Francisco JavierLunov Oleg - Avian cholera is a bacterial disease caused by infection with Pasteurella multocida (P. multocida), which seriously threatens the poultry industry. Liver injury is a key factor in the acute death of infected chickens. This study sought to clarify how P. multocida causes liver injury in broilers, specifically examining liver pyroptosis and the involvement of oxidative stress and inflammation. Experiments with 28-day-old broilers infected with P. multocida showed that post-infection serum indicators were significantly higher for ALT, AST, and T-Bil, but lower for ALB. Histopathological evaluation revealed localized areas of necrosis and structural disruption within liver tissue. Oxidative stress analysis showed that P. multocida infection decreased activities of SOD, GSH-PX, CAT, and T-AOC, while raising MDA and H₂O₂ levels. Liver ELISA results showed notably higher levels of TNF-α, IL-1β, IL-6, IL-18, and IFN-γ in infected liver tissue. Immunofluorescence showed higher levels of 8-OHdG, NLRP3, Caspase-1, and GSDMD in infected tissues versus controls. Transcriptome analysis identified 3392 differentially expressed genes after infection, notably enriched in MAPK signaling pathways. Further analysis at the gene and protein levels confirmed that P. multocida infection activated pathways related to oxidative stress (Keap1, Nrf2, HO-1), inflammation (NF-κB, JNK, p38), and pyroptosis (NLRP3, ASC, Caspase-1, GSDMD, GSDME, IL-1β, IL-18), causing severe liver damage and death in broilers. This study revealed the key role of the MAPK-NLRP3-GSDMD pathway in P. multocida infection, offering new targets and a basis for strategies to prevent and control avian cholera. - Source: PubMed
Publication date: 2026/05/13
Yan DeqiangXu GuangqingCheng YuanWang ZekaiSun YamingWang LonghaoMa FeiyangYan KangHe Shaojun - [This corrects the article DOI: 10.3389/fphar.2021.801048.]. - Source: PubMed
Publication date: 2026/04/29
Gong PinWang PeipeiPi SihuiGuo YuxiPei ShuyaYang WenjuanChang XiangnaWang LanChen Fuxin - In non-small cell lung cancer (NSCLC), mutations in TP53, STK11, and KEAP1 are common in tumors lacking actionable oncogenic drivers and have been associated with poor outcomes, though their prognostic impact remains context-dependent. We evaluated the incidence and prognostic significance of these mutations in actionable mutation-negative NSCLC, stratified by versus recurrent disease. - Source: PubMed
Publication date: 2026/05/08
Vazquez-Urrutia Jorge RaulVenugopal NatashaZhu JunjiaKomiya Takefumi - Isothiocyanates (ITCs), naturally derived from glucosinolates in cruciferous vegetables, represent a versatile class of electrophilic compounds with diverse biological activities. Their characteristic -N=C=S moiety mediates covalent interactions with nucleophiles, and subtle modifications in side-chain structure critically influence their physicochemical properties, reactivity, and biological efficacy. This review aims to annotate the structure-activity relationships (SAR) of ITCs by integrating evidence from mechanistic and pharmacological studies to establish how functional group variations govern bioactivity. An extensive literature was explored, encompassing data on alkyl, aromatic, halogenated, oxidized-sulfur, and chiral ITCs, and electrophilicity index analyses. Comparative evaluation of biological assays, proteomic data, and Nrf2-Keap1 signaling studies enabled a mechanistic mapping of substituent effects. Key findings reveal that electron-withdrawing and oxidized substituents enhance electrophilicity and biological potency; conversely, chain length and lipophilicity exhibit optimal, non-linear correlations with activity. Aromatic and π-conjugated systems confer stability and sustained cellular presence, while stereochemistry contributes to enantioselective differences, as exemplified by sulforaphane enantiomers. Additionally, para-substitution and bifunctional linkers heighten activity through synergistic electronic and steric interactions. Collectively, these insights underscore that ITC bioefficacy arises from a finely balanced interplay between electronic effects and molecular geometry. The review concludes by emphasizing the translational potential of SAR-guided ITC design, covalent proteomics, and in vivo validation to accelerate the rational development of ITC-based therapeutics. - Source: PubMed
Publication date: 2026/05/08
Longkumer PenlisolaSingha BasantaGogoi Partha PratimBoruah NichanSinha Upasana Bora