| First Author | Peng DJ | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 10 | Pages | 5638-47 |
| PubMed ID | 21471442 | Mgi Jnum | J:173100 |
| Mgi Id | MGI:5009733 | Doi | 10.4049/jimmunol.1003801 |
| Citation | Peng DJ, et al. (2011) Noncanonical K27-linked polyubiquitination of TIEG1 regulates Foxp3 expression and tumor growth. J Immunol 186(10):5638-47 |
| abstractText | Earlier, we demonstrated the essential role of Kruppel-like transcription factor, TIEG1, in TGF-beta-induced regulatory T cell (Treg) development. In this article, we demonstrate that IL-6, which promotes Th17 development, abrogated TIEG1 nuclear translocation and inhibited TGF-beta-induced Treg development. Tyrosine kinase Tyk2-mediated phosphorylation of TIEG1 at Tyr179 promoted noncanonical K-27-linked polyubiquitination, which inhibited TIEG1 nuclear translocation. To test the role of TIEG1-regulated Treg/Th17 development in antitumor immunity, we analyzed TRAMP-C2 tumor growth in TIEG1(-/-) mice. The defective Treg development and elevated Th17 response resulted in enhanced immune reactivity in the tumor and inhibition of TRAMP-C2 tumor growth in TIEG1(-/-) mice. Thus, our results uncovered a novel regulatory mechanism that modulates Tregs and may regulate tumor progression. |
