title: The PP2A-Aβ gene is regulated by multiple transcriptional factors including Ets-1, SP1/SP3, and RXRα/β.
abstract: Protein phosphatase-2A (PP-2A) is a major serine/threonine phosphatase abundantly expressed in eukaryotes. PP-2A is a heterotrimer that contains a 65 kD scaffold A subunit, a 36 kD catalytic C subunit, and a regulatory B subunit of variable isoforms ranging from 54-130 kDs. The scaffold subunits, PP2A-Aα/β, act as platforms for both the C and B subunits to bind, and thus are key structural components for PP-2A activity. Mutations in both genes encoding PP2A-Aα and PP2A-Aβ lead to carcinogenesis and likely other human diseases. Our previous work showed that the gene coding for PP2A-Aα is positively regulated by multiple transcription factors including Ets-1, CREB, and AP-2α but negatively regulated by SP-1/SP-3. In the present study, we have functionally dissected the promoter of the mouse PP2A-Aβ gene. Our results demonstrate that three major cis-elements, including the binding sites for Ets-1, SP1/SP3, and RXRα/β, are present in the proximal promoter of the mouse PP2A-Aβ gene. Gel mobility shifting assays reveal that Ets-1, SP1/SP3, and RXRα/β all bind to PP2A-Aβ gene promoter. In vitro mutagenesis and reporter gene activity assays demonstrate that while Ets-1 displays negative regulation, SP1/SP3 and RXRα/β positively regulate the promoter of the PP2A-Aβ gene. Co-expression of the cDNAs encoding Ets-1, SP1/SP3, or RXRα/β and the luciferase reporter gene driven by PP2A-Aβ promoter further confirm their control over the PP2A-Aβ promoter. Finally, ChIP assays demonstrate that Ets-1, SP1/SP3, and RXRα/β can all bind to the PP2A-Aβ gene promoter. Together, our results reveal that multiple transcription factors regulate the PP2A-Aβ gene. Moreover, our results provide important information explaining why PP2A-Aα and PP2A-Aβ display distinct expression levels.
authors: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA.
authors: J
authors: J
authors: Liu
authors: W
authors: W
authors: Ji
authors: S
authors: S
authors: Sun
authors: L
authors: L
authors: Zhang
authors: H-G
authors: HG
authors: Chen
authors: Y
authors: Y
authors: Mao
authors: L
authors: L
authors: Liu
authors: X
authors: X
authors: Zhang
authors: L
authors: L
authors: Gong
authors: M
authors: M
authors: Deng
authors: L
authors: L
authors: Chen
authors: W-J
authors: WJ
authors: Han
authors: P-C
authors: PC
authors: Chen
authors: W-F
authors: WF
authors: Hu
authors: X
authors: X
authors: Hu
authors: Z
authors: Z
authors: Woodward
authors: W-B
authors: WB
authors: Liu
authors: Y-M
authors: YM
authors: Xiao
authors: S-P
authors: SP
authors: Liang
authors: Y
authors: Y
authors: Liu
authors: S-J
authors: SJ
authors: Liu
authors: D W-C
authors: DW
authors: Li
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049410:Luciferases, Renilla / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D054648:Protein Phosphatase 2 / Q000235:genetics* / Q000378:metabolism; D050784:Proto-Oncogene Protein c-ets-1 / Q000502:physiology*; D047490:Retinoid X Receptor alpha / Q000502:physiology*; D049230:Retinoid X Receptor beta / Q000502:physiology*; D017422:Sequence Analysis, DNA; D016329:Sp1 Transcription Factor / Q000502:physiology*; D051705:Sp3 Transcription Factor / Q000502:physiology*; D015533:Transcriptional Activation
chemical_list: C494042:Ets1 protein, mouse; C086766:Ppp2r1b protein, mouse; D050784:Proto-Oncogene Protein c-ets-1; D047490:Retinoid X Receptor alpha; D049230:Retinoid X Receptor beta; D016329:Sp1 Transcription Factor; C497122:Sp3 protein, mouse; D051705:Sp3 Transcription Factor; D049410:Luciferases, Renilla; D054648:Protein Phosphatase 2