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Noncanonical K27-linked polyubiquitination of TIEG1 regulates Foxp3 expression and tumor growth.


ABSTRACT: Earlier, we demonstrated the essential role of Kruppel-like transcription factor, TIEG1, in TGF-?-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-?-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.

SUBMITTER: Peng DJ 

PROVIDER: S-EPMC3914214 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Noncanonical K27-linked polyubiquitination of TIEG1 regulates Foxp3 expression and tumor growth.

Peng Dong-Jun DJ   Zeng Minghui M   Muromoto Ryuta R   Matsuda Tadashi T   Shimoda Kazuya K   Subramaniam Malayannan M   Spelsberg Thomas C TC   Wei Wei-Zen WZ   Venuprasad K K  

Journal of immunology (Baltimore, Md. : 1950) 20110406 10


Earlier, we demonstrated the essential role of Kruppel-like transcription factor, TIEG1, in TGF-β-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-β-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-regula  ...[more]

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