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 journalArticle

47 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 - Jan 1 2002
Externally publishedYes

Fingerprint

Thymocytes
Basic Helix-Loop-Helix Transcription Factors
Proteins
Transcription Factors
Down-Regulation
Apoptosis
T-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Helix-loop-helix proteins regulate pre-TCR and TCR signaling through modulation of Rel/NF-κB activities. / Kim, Dongsoo; Xu, Min; Nie, Lei; Peng, Xiao Cong; Jimi, Eijiro; Voll, Reinhard E.; Nguyen, Thuan; Ghosh, Sankar; Sun, Xiao Hong.

In: Immunity, Vol. 16, No. 1, 01.01.2002, p. 9-21.

Research output: Contribution to journalArticle

Kim, D, Xu, M, Nie, L, Peng, XC, Jimi, E, Voll, RE, Nguyen, T, Ghosh, S & Sun, XH 2002, 'Helix-loop-helix proteins regulate pre-TCR and TCR signaling through modulation of Rel/NF-κB activities', Immunity, vol. 16, no. 1, pp. 9-21. https://doi.org/10.1016/S1074-7613(02)00264-9
Kim, Dongsoo ; Xu, Min ; Nie, Lei ; Peng, Xiao Cong ; Jimi, Eijiro ; Voll, Reinhard E. ; Nguyen, Thuan ; Ghosh, Sankar ; Sun, Xiao Hong. / Helix-loop-helix proteins regulate pre-TCR and TCR signaling through modulation of Rel/NF-κB activities. In: Immunity. 2002 ; Vol. 16, No. 1. pp. 9-21.
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