Noncanonical K27-linked polyubiquitination of TIEG1 regulates Foxp3 expression and tumor growth.
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.
Mesh Terms:
Active Transport, Cell Nucleus, Adoptive Transfer, Animals, Blotting, Western, Cell Nucleus, Cell Proliferation, DNA-Binding Proteins, Flow Cytometry, Forkhead Transcription Factors, Immunoprecipitation, Interleukin-6, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neoplasms, Experimental, Phosphorylation, Polymerase Chain Reaction, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocytes, Regulatory, TYK2 Kinase, Th17 Cells, Transcription Factors, Transforming Growth Factor beta, Ubiquitination
Active Transport, Cell Nucleus, Adoptive Transfer, Animals, Blotting, Western, Cell Nucleus, Cell Proliferation, DNA-Binding Proteins, Flow Cytometry, Forkhead Transcription Factors, Immunoprecipitation, Interleukin-6, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neoplasms, Experimental, Phosphorylation, Polymerase Chain Reaction, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocytes, Regulatory, TYK2 Kinase, Th17 Cells, Transcription Factors, Transforming Growth Factor beta, Ubiquitination
J. Immunol.
Date: May. 15, 2011
PubMed ID: 21471442
View in: Pubmed Google Scholar
Download Curated Data For This Publication
127721
Switch View:
- Interactions 2