The E3 ubiquitin ligase Itch regulates expression of transcription factor Foxp3 and airway inflammation by enhancing the function of transcription factor TIEG1

  • Venuprasad K
  • Huang H
  • Harada Y
 et al. 
  • 70


    Mendeley users who have this article in their library.
  • 116


    Citations of this article.


Transforming growth factor-beta (TGF-beta) signaling in naive T cells induces expression of the transcription factor Foxp3, a 'master' regulator of regulatory T cells (T(reg) cells). However, the molecular mechanisms leading to Foxp3 induction remain unclear. Here we show that Itch-/- T cells were resistant to TGF-beta 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-beta-converted' T(reg) 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.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free