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The F-box-only protein 44 regulates pregnane X receptor protein level by ubiquitination and degradation

Acta Pharmaceutica Sinica B 2023年第11期13卷 4523-4534页

作者： rebecca r.florke gee Andrew D.Huber Jing Wu richa Bajpai Allister J.Loughran Shondra M.Pruett-Miller Taosheng Chen Department of Chemical Biology and Therapeutics St.Jude Children's Research HospitalMemphisTN 38105USA Graduate School of Biomedical Sciences St.Jude Children's Research HospitalMemphisTN 38105USA Center for Advanced Genome Engineering and Department of Cell and Molecular Biology St.Jude Children's Research HospitalMemphisTN 38105USA

Pregnane X receptor(PXr)is a ligand-activated nuclear receptor that transcriptionally upregulates drug-metabolizing enzymes[e.g.,cytochrome P4503A4(CYP3A4)]and *** the regulation of PXr target genes is well-characterized,less is known about the regulation of PXr protein *** screening an rNAi library,we identified the F-box-only protein 44(FBXO44)as a novel E3ligase for *** abundance increases upon knockdown of FBXO44,and,inversely,decreases upon overexpression of *** analysis revealed that FBXO44 interacts with PXr,leading to its ubiquitination and proteasomal degradation,and we determined that the F-box associated domain of FBXO44 and the ligand binding domain of PXr are required for the functional *** summary,FBXO44 regulates PXr protein abundance,which has downstream consequences for CYP3A4 levels and drug-drug *** results of this study provide new insight into the molecular mechanisms that regulate PXr protein level and activity and suggest the importance of considering how modulating E3ubiquitin ligase activities will affect PXr-mediated drug metabolism.

关键词： PXr FBXO44 Ubiquitination Proteasomal degradation CYP3A4 Drug-drug interactions E3 ligase Nuclear receptor

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Mineral concentrations of chickpea and lentil cultivars and breeding lines grown in the *** Northwest

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The Crop Journal 2018年第3期6卷 253-262页

作者： George J.VANDemark Michael A.Grusak rebecca J.Mc gee USDA-ArS Grain Legume Genetics and Physiology Research Unit USDA-ArS Red River Valley Agricultural Research Center

Diseases and health complications caused by mineral deficiencies afflict billions of people globally. Developing pulse crops with elevated seed mineral concentrations can contribute to reducing the incidence of these deficiencies. The objectives of this study were to estimate variance components conditioning seed mineral concentrations of chickpea and lentil grown in Washington and Idaho, determine correlations between different mineral concentrations and between mineral concentrations and yield, 100-seed weight, and days to flowering, and compare seed mineral concentrations between chickpeas and lentils grown in adjacent plots. Genotype effects, although significant in chickpea and lentil for all minerals except selenium, tended to be minimal compared to location, year, and their interaction effects. In both chickpeas and lentils high positive correlations were observed between seed concentrations of phosphorus and potassium, phosphorus and zinc, and potassium and zinc. Correlations between mineral concentration and yield, and mineral concentration and days to 50% flowering were similar for chickpeas and lentils across the majority of minerals. These results may reflect similarities between the two crops in physiological processes for mineral uptake and partitioning. Lentils had higher concentrations of iron and zinc than chickpea when the two crops were grown in adjacent plots,whereas chickpeas had higher concentrations of calcium and manganese. Plant genotypes that are more efficient at obtaining minerals from growing environments will be useful as parental materials to develop improved chickpea and lentil cultivars that have good yield potential coupled with high seed mineral concentrations.

关键词： Chickpea Lentil Mineral Nutrition Pulse

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