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Molecular and Cellular Biology, February 2005, p. 1367-1378, Vol. 25, No. 4
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.4.1367-1378.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Deltex Regulates T-Cell Activation by Targeted Degradation of Active MEKK1

Wen-Hsien Liu1,2 and Ming-Zong Lai1,2,3*

Graduate Institute of Microbiology and Immunology, National Yang-Ming University,1 Institute of Molecular Biology, Academia Sinica,2 Graduate Institute of Immunology, National Taiwan University, Taipei, Taiwan, Republic of China3

Received 20 July 2004/ Returned for modification 9 September 2004/ Accepted 16 November 2004

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.

* Corresponding author. Mailing address: Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan, Republic of China. Phone: (886) 2 2789 9236. Fax: (886) 2 2782 6085. E-mail: mblai{at}ccvax.sinica.edu.tw.

Molecular and Cellular Biology, February 2005, p. 1367-1378, Vol. 25, No. 4
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.4.1367-1378.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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