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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

The PP2A-Aβ Gene is Regulated by Multiple Transcriptional Factors Including Ets-1, SP1/SP3, and RXRα/β.

Protein phosphatase-2A (PP-2A) is a major serine/threonine phosphatase abundantly expressed in eukaryotes. PP-2A is a heterotrimer that contains a 65kD scaffold A subunit, a 36kD catalytic C subunit, and a regulatory B subunit of variable isoforms ranging from 54-130kDs. 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.[1]

References

  1. The PP2A-Aβ Gene is Regulated by Multiple Transcriptional Factors Including Ets-1, SP1/SP3, and RXRα/β. Liu, J., Ji, W., Sun, S., Zhang, L., Chen, H.G., Mao, Y., Liu, L., Zhang, X., Gong, L., Deng, M., Chen, L., Han, W.J., Chen, P.C., Hu, W.F., Hu, X., Woodward, Z., Liu, W.B., Xiao, Y.M., Liang, S.P., Liu, Y., Liu, S.J., Li, D.W. Curr. Mol. Med. (2012) [Pubmed]
 
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