a. The mouseKeap1gene targeting vector (top line), the wild typeKeap1locus (middle line) and the mutant allele generated by homologous integration of the targeting vector (bottom line) are depicted.NLS-LacZ, NeoandDTAgene cassettes are shown along with restriction enzyme sites. The middle line...
4c), whereas overexpression of the deubiquitinase (but not the deubiquitinase-dead mutant) extended the half-life (Fig. 4d). In line with this, KEAP1 was found more ubiquitinated in HepG2 cells depleted of USP25 than in the control cells (Fig. 4e). In addition, there was much less ...
The transfection of V12Rac1, the constitutively active Rac1 mutant, into Keap1-overexpressed cells promoted the basal GST A1 expression, suggesting that Keap1 regulated the basal GST A1 expression during Caco-2 differentiation via Rac1 activation on the formation of E-cadherin-mediated cell-cell ...
Furthermore, in primary macrophage cells expressing C151S mutant KEAP1, at low concentrations, the tricyclic cyanoenone TBE-31 is inactive as an activator of NRF2 as well as an inhibitor of lipopolysaccharide-stimulated gene expression of the pro-inflammatory cytokines IL6 and IL1β. However, ...
KEAP1-Mutant NSCLC: The Catastrophic Failure of a Cell-Protecting Hub 2022, Journal of Thoracic Oncology Citation Excerpt : The KEAP1-NRF2 system represents the major defensive mechanism against oxidative and electrophilic stresses.1,2 Show abstract KEAP1 and TP53 Frame Genomic, Evolutionary, and Im...
Chemical and genetic SHMT suppression increased cellular sensitivity to oxidative stress and cell death. Further, the SHMT inhibitor enhanced the in vivo therapeutic efficacy of paclitaxel (first-line NSCLC therapy inducing oxidative stress) in KEAP1-mutant KL tumours. The data reveal how this highly...
5、 to a significant reduction in NRF2 and downstream targetgene expression selectively in KEAP1 mutant H460 cells. ML385 selectively affects the colony forming abilityor growth of lung cancer cells with gain of NRF2 function 1.体内研究 ML385 in combination with carboplatin leads to a significant...
reductioninNRF2anddownstreamtargetgeneexpressionselectivelyinKEAP1mutantH460cells.ML385selectivelyaffectsthecolonyformingabilityorgrowthoflungcancercellswithgainofNRF2function[1].体内研究ML385incombinationwithcarboplatinleadstoasignificantreductionintumorcellproliferation,demonstratedbyfewerKi-67positivecells.Tumorsamples...
Mutant Magnetospirillum gryphiswaldense cereblon isoform 4 (MSCI4) for two surface tryptophan residues was prepared by molecular cloning as previously described [37]. The DNA fragment harboring residues 1 to 124 of MSCI4 and the PreScission cleavage site in front of the MSCI4 gene was synthesized...
Regarding our previous publication and the established cohort with enrichment for KEAP1/NFE2L2 mutant cases, we intended to systematically assess the value of NQO1 IHC to predict KEAP1/NFE2L2 mutations and the pathway status. In the present study, we used the previously published Cologne cohort ...