Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.11.25 (
MEKK1
)
1,856
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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
.
...
PMID:Deltex regulates T-cell activation by targeted degradation of active MEKK1. 1568 88
