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A Convenient and General Expression Platform for the Production of Secreted Proteins from Human Cells
Published on: July 31, 2012
The basis for IL-2-induced IL-2 receptor alpha chain gene regulation: importance of two widely separated IL-2
H P Kim1, J Kelly, W J Leonard
1Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
The interleukin-2 receptor alpha (IL-2Ralpha) chain is an essential component of high-affinity IL-2 receptors. Accordingly, IL-2Ralpha expression helps to regulate T cell growth and other lymphoid functions. Lineage-restricted and activation-dependent IL-2Ralpha transcription is controlled by three upstream positive regulatory regions (PRRs). We now describe an additional IL-2 response element, PRRIV, within intron 1, in humans and mice. PRRIV activity requires GAS motifs that bind Stat5 proteins and additional upstream HMG-I(Y) binding sites. Moreover, IL-2 induces the binding of HMG-I(Y), Stat5a, and Stat5b in vivo to PRRIV and PRRIII, which also functions as an IL-2 response element. Thus, the IL-2 inducibility of the IL-2Ralpha gene is unexpectedly mediated by two widely separated regulatory Stat5-dependent elements, located both upstream and downstream of the transcription initiation sites.
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