Helix-loop-helix proteins regulate pre-TCR and TCR signaling through modulation of Rel/NF-κB activities

Dongsoo Kim, Min Xu, Lei Nie, Xiao Cong Peng, Eijiro Jimi, Reinhard E. Voll, Thuan Nguyen, Sankar Ghosh, Xiao Hong Sun

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

E2A and HEB are basic helix-loop-helix transcription factors essential for T cell development. Complete inhibition of their activities through transgenic overexpression of their inhibitors Id1 and Tal1 leads to a dramatic loss of thymocytes. Here, we suggest that bHLH proteins play important roles in establishing thresholds for pre-TCR and TCR signaling. Inhibition of their function allows double-negative cells to differentiate without a functional pre-TCR, while anti-CD3 stimulation downregulates bHLH activities. We also find that the transcription factor NF-κB becomes activated in transgenic thymocytes. Further activation of NF-κB exacerbates the loss of thymocytes, whereas inhibition of NF-κB leads to the rescue of double-positive thymocytes. Therefore, we propose that E2A and HEB negatively regulate pre-TCR and TCR signaling and their removal causes hyperactivation and apoptosis of thymocytes.

Original languageEnglish
Pages (from-to)9-21
Number of pages13
JournalImmunity
Volume16
Issue number1
DOIs
Publication statusPublished - 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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