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Abraxas brother protein 1 (ABRO1) is a subunit of the deubiquitinating enzyme BRCC36-containing isopeptidase complex and plays important roles in cellular responses to stress by interacting with its binding partners, such as ubiquitin-specific peptidase 7, p53, activating transcription factor 4, THAP-domain containing 5, and serine hydroxymethyltransferase. However, the transcriptional regulation of ABRO1 remains unexplored. In this study, we identified and characterized the core regulatory elements of the human ABRO1 gene and mapped them to the ABRO1 promoter region. Additionally, 5' rapid amplification of cDNA ends revealed that the transcriptional start site (TSS) was located -13 bp upstream from the start codon. Reporter gene, chromatin immunoprecipitation, and electrophoretic mobility shift assays demonstrated that ABRO1 transcription was regulated through cis-acting elements located in the region -89 to -59 bp upstream of the ABRO1 TSS and that these elements were targeted by yin yang 1 transcription factor (YY1). Moreover, YY1 overexpression increased human ABRO1 mRNA and protein expression, and small-interfering RNA-mediated downregulation of YY1 attenuated ABRO1 expression. These results suggested that YY1 positively regulated human ABRO1 expression by binding to cis-acting elements located in the ABRO1 TSS. Key words: abraxas brother protein 1, BRCC36-containing isopeptidase complex, DNA damage repair, transcriptional regulation, yin yang 1 transcription factor. La proteine ABRO1 (abraxas brother protein 1) est une sous-unite du complexe de desubiquitination BRISC et elle joue un role important dans les reponses cellulaires au stress en interagissant avec ses partenaires de liaison tels que USP7, p53, ATF4, THAP5 et SHMT. Cependant, la regulation transcriptionnelle dABRO1 reste inexploree. Dans cette etude, les auteurs ont identifie et caracterise les principaux elements regulateurs du gene humain ABRO1 et les ont cartographies dans la region du promoteur dABRO1. De plus, l'amplification rapide des extremites 5' (RACE) de lADNc a revele que le site d'initiation de la transcription etait situe a -13 pb en amont du codon d'initiation. Des mesures de l'activite de genes rapporteurs, des immunoprecipitations de chromatine et des retards sur gel ont demontre que la transcription d'ABRO1 etait regulee par des elements en cis situes dans la region -89 a -59 pb en amont du site d'initiation de la transcription dABRO1 et que ces elements etaient cibles par le facteur de transcription yin yang 1 (YY1). Par ailleurs, la surexpression de YY1 augmentait l'expression de l'ARNm et de la proteine ABRO1 humaine, et la regulation a la baisse de YY1 mediee par un petit ARN interferent attenuait l'expression d'ABRO1. Ces resultats suggerent que YY1 a regule positivement l'expression d'ABRO1 humain en se liant aux elements en cis situes au site d'initiation de la transcription d'ABRO1. [Traduit par la Redaction] Mots-cles : ABRO1, BRISC, reparation des dommages a l'ADN, regulation transcriptionnelle, facteur de transcription yin yang 1., Introduction Abraxas brother protein 1 (ABRO1) encodes a 415-amino acid component of the breast cancer (BRCA) 1/BRCA2-containing complex subunit 3-Lys-63-specific deubiquitinase (BRCC36)-containing isopeptidase complex (BRISC); a deubiquitinating (DUB) enzyme (Cooper [...]

Glycerol kinase (GYK) plays a critical role in hepatic metabolism by converting glycerol to glycerol 3-phosphate in an ATP-dependent reaction. GYK isoform bis the only glycerol kinase presentinwhole cells, and has a non-enzymatic moonlighting function in the nucleus. GYK isoform b acts as a co-regulator of nuclear receptor subfamily 4 group A1 (NR4A1) and participates in the regulation of hepatic glucose metabolism by protein--protein interaction with NR4A1. Herein, GYK expression was found to upregulate the expression of NR4A1-mediated lipid metabolism-related genes (SREBP1C, FASN, ACACA, and GPAM) in HEK293T and L02 cells, and in mouse in vivo studies. GYK expression increased blood levels of cholesterol, triglyceride, and high-density lipoprotein cholesterol, but not low-density lipoprotein cholesterol levels. It enhanced the transcriptional activity of Nr4a1 target genes by negatively cooperating with NR4A1 and its enzymatic activity or by other undefined moonlighting functions. This enhancement was observed in both normal and diabetic mice. We also found a feed-forward regulation loop between GYK and NR4A1, servingas partof aGYK-NR4A1 regulatory mechanismin hepatic metabolism. Thus, GYK regulates the effect ofNR4A1 on hepatic lipid metabolism in normal and diabetic mice, partially through the cooperation of GYK and NR4A1. Key words: glycerol kinase, NR4A1, lipid metabolism, feed-forward regulation, diabetes. La glycerol kinase (GYK) joue un role cle dans le metabolisme hepatique en convertissant le glycerol en glycerol-3-phosphate par une reaction dependante de l'ATP. L'isoforme b de la GYK est la seule kinase presente dans toutes les cellules et elle exerce une fonction non enzymatique dans le noyau. L'isoforme b de la GYK agit comme co-regulateur de NR4A1 (nuclear receptor subfamily 4 group A1) et participe a la regulation du metabolisme du glucose hepatique par des interactions proteine-proteine avec NR4A1. Ici, l'expression de GYK s'est averee reguler a la hausse l'expression de genes lies au metabolisme des lipides medie par NR4A1 (SREBP1C, FASN, ACACA et GPAM) chez les cellules HEK293T et L02, ainsi que lors d'etudes in vivo chez la souris. L'expression de GYK augmentait les niveaux de cholesterol, de triglycerides et de cholesterol HDL dans le sang, mais pas les niveaux de cholesterol LDL. Elle accroissait l'activite transcriptionnelle des genes cibles de Nr4a1 en interagissant negativement avec NR4A1 et son activite enzymatique ou par d'autres fonctions mal definies. Cet accroissement etait observe tant chez les souris normales que chez les souris diabetiques. Les auteurs ont aussi trouve une boucle de regulation ouverte entre GYK et NR4A1, servant en partie comme un mecanisme regulateur GYK-NR4A1 dans le metabolisme hepatique. Ainsi, GYK regule l'effet de NR4A1 dans le metabolisme hepatique des lipides chez les souris normales et diabetiques, partiellement par l'interaction entre GYK et NR4A1. [Traduit par la Redaction] Mots-cles : glycerol kinase, NR4A1, metabolisme des lipides, regulation ouverte, diabete., Introduction Nuclear receptor subfamily 4 group A1 (NR4A1/Nur77) belongs to the NR4A subfamily of nuclear receptors that function as ligand-independent transcription factors and immediate early response genes (Pearen and Muscat [...]

Flexible electronic materials with high‐dielectric constant (ɛ) and breakdown strength (Eb) but low loss is pursued. Encapsulation of conductive fillers with various insulating shells represents a promising strategy to inhibit dielectric loss or leakage current. In this work, aluminum oxide (Al2O3) encapsulated silicon (Si) core‐shell structured particles were prepared through a sol–gel approach, and then were incorporated with poly(vinylidene fluoride) (PVDF). The dielectric properties of PVDF composites with various fillers are investigated under varying frequencies. The findings demonstrate that a Al2O3 shell was formed outside the original Si, and that the Si@Al2O3/PVDF exhibit a high ɛ and elevated Eb but signally suppressive loss and restrained conductivity when compared with raw Si. The Al2O3 interlayer not only enhances the interface compatibility between the filler and the matrix and promotes interface polarizations, but also suppresses the loss and leakage current through preventing adjacent Si from directly contacting. The optimized dielectric performances can be achieved via tailoring the Al2O3 shell thickness. Furthermore, the theoretic fitting of experimental results by the Havriliak‐Negami equation deciphers the Al2O3 interlayer' impact on the polarization mechanism. The resulting Si@Al2O3/PVDF composites with high ε but low loss, as well as boosted Eb, reveal potential applications in electrical systems. [ABSTRACT FROM AUTHOR]

Selective inhibition of the endogenous coagulation pathway is a promising strategy for developing new anticoagulants. Fucosylated glycosaminoglycan (FG), a structurally complex glycosaminoglycan, has distinct anticoagulant properties, especially the strong intrinsic factor Xase inhibitory activity that is recognized as a new target with potential physiological and therapeutic applications. Detailed knowledge of FG structures is necessary for developing a clinically effective intrinsic FXase inhibitor. However, challenges remain to elucidate FG structures as a basis for pharmaceutical development. Herein, using the highly selective β-elimination method, oligosaccharides with regular structures were prepared from the depolymerization products. Analysis of oligosaccharides further confirmed the precise structural sequence of the FG. Furthermore, biological activity assay suggested that these pure homogeneous oligosaccharides, particularly an octasaccharide, exhibit strong inhibition of the intrinsic coagulation pathway by inhibiting human intrinsic factor Xase. Our finding is significant for discovery of a new class of anticoagulant agents as intrinsic factor Xase inhibitors. [ABSTRACT FROM AUTHOR]