Functionally Distinct NF-κB Binding Sites in the Immunoglobulin κ and IL-2 Receptor α Chain Genes

Abstract

The interleukin-2 receptor alpha (IL-2R alpha) chain gene contains a sequence similar to the immunoglobulin (Ig) kappa (kappa) enhancer NF-kappa B binding site. This site, which is bound by the nuclear protein, NF-kappa B, is critical for Ig kappa gene expression. The major T cell nuclear factor that binds to the IL-2R alpha site in vitro appears indistinguishable from NF-kappa B. NF-kappa B binds to IL-2R alpha and kappa sequences with similar affinities; however, only the kappa site potently activates transcription from heterologous promoters. Thus, high-affinity NF-kappa B binding in vitro cannot be equated with transcriptional activation in vivo. Mutation of the NF-kappa B binding site in the context of an IL-2 R alpha promoter construct markedly diminished promoter activity in human T cell lymphotropic virus type I (HTLV-I)-transformed MT-2 cells but not in phorbol myristate acetate-stimulated Jurkat T cells.

Transcriptional regulation via the NF-κB signaling module

“…Although the Ig kB site (5 0 -GGGACTTTCC-3 0 ) and the IL-2Ra kB site are both high-affinity NF-kB-binding sites, they are not functionally equivalent, as determined by swap experiments (Cross et al, 1989). These observations suggested that the NF-kB dimer specificity of promoters may be context-and stimulus-dependent, making it unlikely that NF-kB-DNA interactions alone determine specificity of NF-kB-responsive promoters.…”

The role of Stat5a and Stat5b in signaling by IL-2 family cytokines

“…As illustrated in Figure 5, the human IL-2Ra promoter contains three well-characterized positive regulatory regions (PRRs). PRRI is located at 7299 to 7228 relative to the major transcription initiation site and binds to NF-kB serum response factor (SRF) and Sp1 (Ballard et al, 1989;Bohnlein et al, 1988;Cross et al, 1989;Leung and Nabel, 1988;Roman et al, 1990;Toledano et al, 1990). PRRII spans the region between 7137 to 764 and binds to an Ets family protein, Elf-1, and the high mobility group proteins, HMG-I/Y Lecine et al, 1996).…”

Essential Role of Human Leukocyte Antigen-encoded Proteasome Subunits in NF-κB Activation and Prevention of Tumor Necrosis Factor-α-induced Apoptosis

“…Nuclear factor-B (NF-B) 1 /Rel superfamily is a transcription factor that contributes to the ability of the immune system to respond rapidly to foreign antigens (1)(2)(3)(4)(5)(6). NF-B is activated in response to various extracellular stimuli, including interleukin 1 (IL-1), tumor necrosis factor-␣ (TNF-␣), lipopolysaccharide, and phorbol esters (2,(7)(8)(9)(10)(11)(12).…”

“…NF-B is activated in response to various extracellular stimuli, including interleukin 1 (IL-1), tumor necrosis factor-␣ (TNF-␣), lipopolysaccharide, and phorbol esters (2,(7)(8)(9)(10)(11)(12). NF-B is implicated in the regulation of genes that contribute to cytokine generation, expression of cell surface adhesion molecules, and processing and presentation of major histocompatibility complex (MHC) or human leukocyte antigen (HLA) class I-restricted antigens (1)(2)(3)(4)(5)(6). NF-B also plays an important role in preventing apoptosis and in activating signaling pathways that contribute to cellular transformation and development (12)(13)(14)(15)(16)(17)(18)(19)(20).…”