| First Author | Liu WH | Year | 2005 |
| Journal | Mol Cell Biol | Volume | 25 |
| Issue | 4 | Pages | 1367-78 |
| PubMed ID | 15684388 | Mgi Jnum | J:95987 |
| Mgi Id | MGI:3528526 | Doi | 10.1128/MCB.25.4.1367-1378.2005 |
| Citation | Liu WH, et al. (2005) Deltex regulates T-cell activation by targeted degradation of active MEKK1. Mol Cell Biol 25(4):1367-78 |
| abstractText | Deltex is known as a Notch signal mediator, but its physiological action mechanism is poorly understood. Here we identified a new regulatory role of Deltex in T-cell activation. Deltex expression was constitutive in resting T cells and was reduced upon T-cell receptor (TCR)-stimulated activation. The biological role of Deltex is supported by the enhanced T-cell activation when Deltex1 was down-regulated by small interfering RNA. Overexpression of Deltex1 suppressed T-cell activation but not the proximal TCR activation events. The impaired activation of mitogen-activated protein kinase by Deltex could be partly attributed to a selective down-regulation of MEKK1 protein in T cells. We further found that Deltex promoted degradation of the C-terminal catalytic fragment of MEKK1 [MEKK1(C)]. Deltex1 interacted directly with MEKK1(C) and stimulated the ubiquitination of MEKK1(C) as shown by in vivo and in vitro ubiquitination analysis. Therefore, MEKK1(C), the dominant form of MEKK1 in T cells, is a target of Deltex E3 ubiquitin ligase. Our results reveal a novel mechanism as to how Deltex selectively suppresses T-cell activation through degradation of a key signaling molecule, MEKK1. |
