| First Author | Zhao Y | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 47 | Pages | 40520-30 |
| PubMed ID | 21931165 | Mgi Jnum | J:178157 |
| Mgi Id | MGI:5297627 | Doi | 10.1074/jbc.M111.292961 |
| Citation | Zhao Y, et al. (2011) The Deubiquitinase CYLD Targets Smad7 Protein to Regulate Transforming Growth Factor beta (TGF-beta) Signaling and the Development of Regulatory T Cells. J Biol Chem 286(47):40520-30 |
| abstractText | CYLD is a lysine 63-deubiquitinating enzyme that inhibits NF-kappaB and JNK signaling. Here, we show that CYLD knock-out mice have markedly increased numbers of regulatory T cells (Tregs) in peripheral lymphoid organs but not in the thymus. In vitro stimulation of CYLD-deficient naive T cells with anti-CD3/28 in the presence of TGF-beta led to a marked increase in the number of Foxp3-expressing T cells when compared with stimulated naive control CD4(+) cells. Under endogenous conditions, CYLD formed a complex with Smad7 that facilitated CYLD deubiquitination of Smad7 at lysine 360 and 374 residues. Moreover, this site-specific ubiquitination of Smad7 was required for activation of TAK1 and p38 kinases. Finally, knockdown of Smad7 or inhibition of p38 activity in primary T cells impaired Treg differentiation. Together, our results show that CYLD regulates TGF-beta signaling function in T cells and the development of Tregs through deubiquitination of Smad7. |
