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

Dong Jun Peng, Minghui Zeng, Ryuta Muromoto, Tadashi Matsuda, Kazuya Shimoda, Malayannan Subramaniam, Thomas C. Spelsberg, Wei Zen Wei, K. Venuprasad

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

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-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.

Original languageEnglish (US)
Pages (from-to)5638-5647
Number of pages10
JournalJournal of Immunology
Volume186
Issue number10
DOIs
StatePublished - May 15 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Peng, D. J., Zeng, M., Muromoto, R., Matsuda, T., Shimoda, K., Subramaniam, M., Spelsberg, T. C., Wei, W. Z., & Venuprasad, K. (2011). Noncanonical K27-linked polyubiquitination of TIEG1 regulates Foxp3 expression and tumor growth. Journal of Immunology, 186(10), 5638-5647. https://doi.org/10.4049/jimmunol.1003801