Article abstract
Nature Immunology 9, 245 - 253 (2008)
Published online: 17 February 2008 | doi:10.1038/ni1564
The E3 ubiquitin ligase Itch regulates expression of transcription factor Foxp3 and airway inflammation by enhancing the function of transcription factor TIEG1
K Venuprasad1, Haining Huang1, Yousuke Harada1, Chris Elly1, Malayannan Subramaniam2, Thomas Spelsberg2, Jin Su1 & Yun-Cai Liu1
Abstract
Transforming growth factor-
(TGF-) signaling in naive T cells induces expression of the transcription factor Foxp3, a 'master' regulator of regulatory T cells (Treg cells). However, the molecular mechanisms leading to Foxp3 induction remain unclear. Here we show that Itch-/- T cells were resistant to TGF- treatment and had less Foxp3 expression. The E3 ubiquitin ligase Itch associated with and promoted conjugation of ubiquitin to the transcription factor TIEG1. Itch cooperated with TIEG1 to induce Foxp3 expression, which was reversed by TIEG1 deficiency. Functionally, 'TGF--converted' Treg cells generated from TIEG1-deficient mice were unable to suppress airway inflammation in vivo. These results suggest TIEG and Itch contribute to a ubiquitin-dependent nonproteolytic pathway that regulates inducible Foxp3 expression and the control of allergic responses.
- Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
- Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Correspondence to: Yun-Cai Liu1 e-mail: yuncail@liai.org
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