Ras-ERK MAPK cascade regulates GATA3 stability and Th2 differentiation through ubiquitin-proteasome pathway

Masakatsu Yamashita, Ryo Shinnakasu, Hikari Asou, Motoko Kimura, Akihiro Hasegawa, Kahoko Hashimoto, Naoya Hatano, Masato Ogata, Toshinori Nakayama

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

Differentiation of naive CD4 T cells into Th2 cells requires protein expression of GATA3. Interleukin-4 induces STAT6 activation and subsequent GATA3 transcription. Little is known, however, on how T cell receptor-mediated signaling regulates GATA3 and Th2 cell differentiation. Here we demonstrated that T cell receptor-mediated activation of the Ras-ERK MAPK cascade stabilizes GATA3 protein in developing Th2 cells through the inhibition of the ubiquitin-proteasome pathway. Mdm2 was associated with GATA3 and induced ubiquitination on GATA3, suggesting its role as a ubiquitin-protein isopeptide ligase for GATA3 ubiquitination. Thus, the Ras-ERK MAPK cascade controls GATA3 protein stability by a post-transcriptional mechanism and facilitates GATA3-mediated chromatin remodeling at Th2 cytokine gene loci leading to successful Th2 cell differentiation.

Original languageEnglish
Pages (from-to)29409-29419
Number of pages11
JournalJournal of Biological Chemistry
Volume280
Issue number33
DOIs
Publication statusPublished - Aug 19 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Yamashita, M., Shinnakasu, R., Asou, H., Kimura, M., Hasegawa, A., Hashimoto, K., Hatano, N., Ogata, M., & Nakayama, T. (2005). Ras-ERK MAPK cascade regulates GATA3 stability and Th2 differentiation through ubiquitin-proteasome pathway. Journal of Biological Chemistry, 280(33), 29409-29419. https://doi.org/10.1074/jbc.M502333200