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• W2080474420 endingPage "75" @default.
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• W2080474420 abstract "The serine–threonine protein phosphatase 2A (PP2A) is a heterotrimeric enzyme family that plays an essential regulatory role in cell growth, differentiation, and apoptosis. Mutations in the genes encoding PP2A-Aα/β subunits are associated with tumorigenesis and other human diseases. To explore whether genetic variations in the promoter region of the PP2A-Aα gene (PPP2R1A) and their frequent haplotypes in the Han Chinese population have an impact on transcriptional activity, we collected DNA samples from 63 healthy Chinese donors and searched for genetic variations in the 5′-flanking promoter region of PPP2R1A (PPP2R1Ap). Haplotypes were characterized by Haploview analysis and individual subcloning. A set of molecular and functional experiments was performed using reporter genes and electrophoretic mobility shifting assay (EMSA). Seven genetic variations were identified within the promoter locus (2038 bp) of PPP2R1A. Linkage disequilibrium (LD) patterns and haplotype profiles were analyzed using the identified genetic variants. Using serially truncated human PPP2R1A promoter luciferase constructs, we found that a 685 bp (−448 nt to +237 nt) fragment around the transcription start site (TSS) was the core promoter region. Individual subcloning revealed the existence of six haplotypes in this proximal promoter region of PPP2R1Ap. Using luciferase reporter assays, we found that different haplotypes bearing different variant alleles exhibit distinct promoter activities. The EMSA revealed that the −241 −/G variant influences DNA–protein interactions involving the transcription factor NF-κB, which may regulate the activity of the PPP2R1A proximal promoter. Our findings suggest that functional genetic variants in the proximal promoter of the PP2A-Aα gene and their haplotypes are critical in the regulation of transcriptional activation." @default.
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• W2080474420 date "2011-11-01" @default.
• W2080474420 modified "2023-09-29" @default.
• W2080474420 title "Identification and functional analyses of polymorphism haplotypes of protein phosphatase 2A-Aα gene promoter" @default.
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• W2080474420 doi "https://doi.org/10.1016/j.mrfmmm.2011.08.004" @default.
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