Reduction of Runx1 transcription factor activity up-regulates Fas and Bim expression and enhances the apoptotic sensitivity of double positive thymocytes

Natsumi Abe, Kazuyoshi Kohu, Hidetaka Ohmori, Keitaro Hayashi, Toshio Watanabe, Katsuto Hozumi, Takehito Sato, Sonoko Habu, Masanobu Satake

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

The death or survival of double positive (DP) thymocytes is determined by the strength of their TCR signaling. Of the three Runx family proteins, the DP cells only express the Runx1 transcription factor. We introduced and expressed in murine thymocytes the Runt domain of Runx1, which antagonizes the activity of endogenous Runx1. The Runt transgenic DP thymocytes expressed higher levels of the proapoptotic molecules Fas and Bim compared with the wild-type cells. Furthermore, the Runt transgenic cells were more susceptible to apoptosis induced by the artificial cross-linking of the TCR by the anti-CD3 Ab. TMs susceptibility was partially abrogated by the lpr/lpr background. In addition, Runx1:HY-TCR-double transgenic DP thymocytes were resistant to the apoptosis induced by the endogenously presented HY Ag. We propose that Runx1 functions to suppress the apoptotic sensitivity of DP thymocytes in the context of TCR signaling.

Original languageEnglish
Pages (from-to)4475-4482
Number of pages8
JournalJournal of Immunology
Volume175
Issue number7
DOIs
Publication statusPublished - 2005 Oct 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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