| First Author | Yang Y | Year | 2006 |
| Journal | J Biol Chem | Volume | 281 |
| Issue | 46 | Pages | 34989-96 |
| PubMed ID | 17012234 | Mgi Jnum | J:117232 |
| Mgi Id | MGI:3695843 | Doi | 10.1074/jbc.M608078200 |
| Citation | Yang Y, et al. (2006) Id1 potentiates NF-kappaB activation upon T cell receptor signaling. J Biol Chem 281(46):34989-96 |
| abstractText | 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. |
