1989
DOI: 10.1126/science.2497518
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Kappa B-Specific DNA Binding Proteins: Role in the Regulation of Human Interleukin-2 Gene Expression

Abstract: Transcriptional activation of the human interleukin-2 (IL-2) gene, like induction of the IL-2 receptor alpha (IL-2R alpha) gene and the type 1 human immunodeficiency virus (HIV-1), is shown to be modulated by a kappa B-like enhancer element. Mutation of a kappa B core sequence identified in the IL-2 promoter (-206 to -195) partially inhibits both mitogen- and HTLV-I Tax-mediated activation of this transcription unit and blocks the specific binding of two inducible cellular factors. These kappa B-specific prote… Show more

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Cited by 313 publications
(189 citation statements)
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“…NF-‹ B was first described as necessary for inducible activation of the Th1 cytokine genes IL-2 [25][26][27] and IFN-+ [28,29]. Subsequently, NF-‹ B was found to participate in activation of many inflammatory cytokine genes and also other genes [20].…”
Section: Discussionmentioning
confidence: 99%
“…NF-‹ B was first described as necessary for inducible activation of the Th1 cytokine genes IL-2 [25][26][27] and IFN-+ [28,29]. Subsequently, NF-‹ B was found to participate in activation of many inflammatory cytokine genes and also other genes [20].…”
Section: Discussionmentioning
confidence: 99%
“…This transcription factor plays an important role in activating the IL-2 promoter in T cells (Hoyos et al, 1989;Shibuya et al, 1989;Baumann et al, 1991;Briegel et al, 1991) (and Figure 3) as well as numerous other promoters, in many cell types (Baeuerle, 1991). Therefore understanding how calcineurin activates NF-xB might provide generalizable insights into the mechanisms by which this transcription factor is controlled.…”
Section: Discussionmentioning
confidence: 99%
“…DNA sequences recognized by these factors are found within the 300 base pairs preceding the IL-2 gene transcription start site. There are minimally five factors, uniquely defined by nucleotide sequence recognition, essential for (ionomycin+PMA)-induced transcription from the IL-2 gene promoter: NF-AT, which binds the IL-2E element (Durand et al, 1988), NF-xB, which binds the IL-2C element (Baumann et al, 1991;Briegel et al, 1991;Hoyos et al, 1989;Shibuya et al, 1989), which recognizes a sequence within the IL-2B element (Jain et al, 1992a,b;Northrop et al, 1992), and OAP (Ullman et al, 1991) and Oct-I (Kamps et al, 1990), which function together, each recognizing an independent sequence within the IL-2A element (Durand et al, 1988 (Mattila et al, 1990). (ii) An NF-xB-dependent enhancer is responsive to PMA, unresponsive to ionomycin, but very responsive to ionomycin in the presence of PMA.…”
Section: Introductionmentioning
confidence: 99%
“…Together with b-and a common g-chain, IL-2Ra forms the high-affinity IL-2 receptor, which permits signaling at low IL-2 concentrations. A complementary observation that the promoter for the IL-2 gene is also activated by Tax (Hoyos et al, 1989;McGuire et al, 1993;Good et al, 1996) led to an unifying hypothesis of T-cell proliferation through an autocrine IL-2/IL-2R loop. Actually, this hypothesis insufficiently explains ATL biology and transformed growth in culture since most Tax or HTLV-1-immortalized T-cells still require exogenous IL-2 and do not detectably express either IL-2 mRNA or protein (Akagi and Shimotohno, 1993;Schmitt et al, 1998;Chung et al, 2003).…”
Section: Il-2 and Il-15mentioning
confidence: 99%