The same 50-kDa cellular protein binds to the negative regulatory elements of the interleukin 2 receptor alpha-chain gene and the human immunodeficiency virus type 1 long terminal repeat.
- 1 November 1989
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 86 (21), 8526-8530
- https://doi.org/10.1073/pnas.86.21.8526
Abstract
We have investigated the biochemical basis for negative regulation of interleukin 2 receptor .alpha.-chain (IL-2R.alpha.) gene expression. Transient transfection studies employing internally deleted forms of the IL-2R.alpha. promoter localized a negative regulatory element (NRE) between nucleotides-400 and -368 relative to the major distal transcription start (cap) site. This 31-base-pair (bp) element is involved in the attenuation of both basal and inducible IL-2R.alpha. promoter activity. Comparison of this IL-2R.alpha. NRE with other known regulatory motifs revealed an 11-bp core element (TTCATCCCAGG) that was strikingly similar to a protein-binding domain within the long terminal repeat of the type 1 human immunodeficiency virus (HIV-1). This viral domain has been previously implicated in the negative control of HIV-1 gene expression. In vitro protein-DNA binding studies demonstrated that the same constitutively expressed .apprxeq. 50-kDa protein (SP-50) specifically bound to both the IL-2R.alpha. and HIV-1 NRE core elements. Mutation of the 11-bp IL-2R.alpha. NRE core element, which disrupted protein binding, significantly augmented basal as well as Tax protein-or phorbol ester-induced IL-2R.alpha. promoter activity in vivo, suggesting that SP-50 functions as a transcriptional silencer.This publication has 29 references indexed in Scilit:
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