title: Id1 potentiates NF-kappaB activation upon T cell receptor signaling.
abstract: E2A and HEB are basic helix-loop-helix transcription factors that play important roles in T cell development. Expression of Id1, one of their inhibitors, severely impairs T cell development in transgenic mice. Aberrant activation of NF-kappaB transcription factors has been shown to contribute to the developmental defects, but it is not clear whether NF-kappaB activation is directly due to Id1 expression or is secondary to an abnormal thymic environment in Id1 transgenic mice. Here, by using a T cell line model, we demonstrate that Id1 expression stimulates basal levels of NF-kappaB activity and further enhances NF-kappaB activation upon T cell receptor (TCR) signaling achieved by anti-CD3 and anti-CD28 stimulation. Activation of NF-kappaB is partially mediated by the classical pathway involving the interaction between the regulatory subunit, NF-kappaB essential modulator (NEMO), and the catalytic subunit, IkappaB kinase beta. However, a NEMO-independent pathway also appears to be at play. Id1-potentiated activation of NF-kappaB leads to overproduction of cytokines such as tumor necrosis factor alpha and interferon-gamma in a T cell line as well as in thymocytes. Among members of the NF-kappaB family, c-Rel appears to be preferentially activated by Id1, especially during TCR stimulation. Consistently, c-rel deficiency diminishes tumor necrosis factor alpha and interferon-gamma expression induced by Id1 and TCR signaling.
authors.affiliation: Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
authors.forename: Yuanzheng
authors.initials: Y
authors.lastname: Yang
authors.forename: Hsiou-Chi
authors.initials: HC
authors.lastname: Liou
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Sun
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D005786:Gene Expression Regulation; D020573:Genes, rel / Q000502:physiology; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism; D051820:TCF Transcription Factors / Q000378:metabolism; D058125:Transcription Factor 7-Like 1 Protein; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D018106:CD28 Antigens; D017252:CD3 Complex; D020672:I-kappa B Proteins; C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; D051820:TCF Transcription Factors; C544912:TCF7L1 protein, human; C544913:Tcf7l1 protein, mouse; D058125:Transcription Factor 7-Like 1 Protein; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D051550:I-kappa B Kinase