A dominant-negative mutant of c-Jun inhibits cell cycle progression during the transition of CD4(-)CD8(-) to

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Updated: Aug 3, 2026

Analysis of Cell Cycle Position in Mammalian Cells
12:19

Analysis of Cell Cycle Position in Mammalian Cells

Published on: January 21, 2012

L B King1, E Tolosa, J M Lenczowski

  • 1Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda MD 20892, USA.

International Immunology
|July 28, 1999
PubMed

Insights

Jun/Fos transcription factors are crucial for T cell development. Inhibiting c-Jun in thymocytes reduced T cell numbers by hindering proliferation during development.

Area of Science:

  • Immunology
  • Developmental Biology
  • Molecular Biology

Background:

  • Jun/Fos transcription factors are vital for T cell receptor (TCR)-mediated events in mature T cells.
  • Their specific roles in thymocyte development remain largely uncharacterized.

Purpose of the Study:

  • To investigate the function of Jun/Fos-containing transcription factors during thymocyte development.
  • To elucidate the impact of inhibiting c-Jun activity on T cell maturation in vivo.

Main Methods:

  • Generation of transgenic mice expressing a trans-dominant-negative mutant of c-Jun (TAM-67) specifically in thymocytes.
  • Analysis of AP-1-responsive gene expression (c-jun, IL-2) in stimulated thymocytes.
  • Assessment of thymocyte cellularity, subset distribution (CD4, CD8, CD25), apoptosis rates, and cell cycle progression.

Main Results:

  • Expression of TAM-67 in thymocytes inhibited the upregulation of AP-1-responsive genes upon stimulation.
  • TAM-67 transgenic mice exhibited a significant decrease (approx. 50%) in thymic cellularity, mainly due to reduced CD4(+)CD8(+) thymocyte numbers.
  • The reduction in CD4(+)CD8(+) thymocytes was attributed to decreased proliferation of CD4(-)CD8(-)CD25(-) cells, not increased apoptosis.

Conclusions:

  • Jun/Fos-containing transcription factors are essential regulators of thymocyte proliferation.
  • These factors promote the proliferative expansion necessary for the transition from CD4(-)CD8(-) to CD4(+)CD8(+) stages during T cell development.

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