RESUMO
Histone methyl transferase EZH2 (Enhancer of Zeste Homolog 2) is generally associated with H3K27 methylation and gene silencing, as a member of the polycomb repressor 2 (PRC2) complex. Immunoprecipitation and mass spectrometry of the EZH2-protein interactome in estrogen receptor positive, breast cancer-derived MCF7 cells revealed EZH2 interactions with subunits of chromatin remodeler SWI/SNF complex and TRIM28, which formed a complex with EZH2 distinct from PRC2. Unexpectedly, transcriptome profiling showed that EZH2 primarily activates, rather than represses, transcription in MCF7 cells and with TRIM28 co-regulates a set of genes associated with stem cell maintenance and poor survival of breast cancer patients. TRIM28 depletion repressed EZH2 recruitment to chromatin and expression of this gene set, in parallel with decreased CD44hi/CD24lo mammosphere formation. Mammosphere formation, inhibited by EZH2 depletion, was rescued by ectopic expression of EZH2 but not by TRIM28 expression or by EZH2 mutated at the region (pre-SET domain) of TRIM28 interaction. These results support PRC2-independent functions of EZH2 and TRIM28 in activation of gene expression that promotes mammary stem cell enrichment and maintenance.
Assuntos
Neoplasias da Mama/patologia , Proteínas Cromossômicas não Histona/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Células-Tronco Neoplásicas/fisiologia , Proteínas Repressoras/metabolismo , Esferoides Celulares/fisiologia , Fatores de Transcrição/metabolismo , Neoplasias da Mama/genética , Adesão Celular/genética , Diferenciação Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Células MCF-7 , Células-Tronco Neoplásicas/patologia , Ligação Proteica , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Proteína 28 com Motivo Tripartido , Células Tumorais CultivadasRESUMO
We report an analysis of the nuclear dependence of the yield of Drell-Yan dimuons from the 800 GeV/c proton bombardment of 2H, C, Ca, Fe, and W targets. Employing a new formulation of the Drell-Yan process in the rest frame of the nucleus, this analysis examines the effect of initial-state energy loss and shadowing on the nuclear-dependence ratios versus the incident proton's momentum fraction and dimuon effective mass. The resulting energy loss per unit path length is -dE/dz = 2.32+/-0.52+/-0.5 GeV/fm. This is the first observation of a nonzero energy loss of partons traveling in a nuclear environment.
RESUMO
Bis(trifluoromethyl)disulfide (TFD), used as an industrial fumigant, was found to generate a thiyl free radical as seen by EPR/spin trapping. Oxygen appears to be an absolute requirement for radical production. The results obtained in this investigation implicate the production of thiyl and reactive oxygen species (ROS), superoxide radical anion and hydroxyl radicals, during TFD autoxidation. The rate of production of these free radical intermediates was found to increase in the presence of iron(III) and copper(II). In addition, the metal ion chelator DETAPAC and ROS scavengers ethanol, mannitol, and PEG-SOD/catalase were found to inhibit free radical production. Reactive oxygen species were not formed when a high-potency zinc plus antioxidant, ZE caps, was present. These results provide support for the pro-oxidation of TFD and a protective role for zinc.
