c-Myc mediates pre-TCR-induced proliferation but not developmental progression

Marei Dose, Irum Khan, Zhuyan Guo, Damian Kovalovsky, Andreas Krueger, Harald Von Boehmer, Khashayarsha Khazaie, Fotini Gounari

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Constitutive and cell-autonomous signals emanating from the pre-T-cell receptor (pre-TCR) promote proliferation, survival and differentiation of immature thymocytes. We show here that induction of pre-TCR signaling resulted in rapid elevation of c-Myc protein levels. Cre-mediated thymocyte-specific ablation of c-Myc in CD25+CD44- thymocytes reduced proliferation and cell growth at the pre-TCR checkpoint, resulting in thymic hypocellularity and a severe reduction in CD4+CD8+ thymocytes. In contrast, c-Myc deficiency did not inhibit pre-TCR-mediated differentiation or survival. Myc-/- double-negative (DN) 3 cells progressed to the double-positive (DP) stage and up-regulated TCRαβ surface expression in the absence of cell proliferation, in vivo as well as in vitro. These observations indicate that distinct signals downstream of the pre-TCR are responsible for proliferation versus differentiation, and demonstrate that c-Myc is only required for pre-TCR-induced proliferation but is dispensable for developmental progression from the DN to the DP stage.

Original languageEnglish (US)
Pages (from-to)2669-2677
Number of pages9
JournalBlood
Volume108
Issue number8
DOIs
StatePublished - Oct 15 2006

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Dose, M., Khan, I., Guo, Z., Kovalovsky, D., Krueger, A., Von Boehmer, H., Khazaie, K., & Gounari, F. (2006). c-Myc mediates pre-TCR-induced proliferation but not developmental progression. Blood, 108(8), 2669-2677. https://doi.org/10.1182/blood-2006-02-005900