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IL-7R-dependent survival and differentiation of early T-lineage progenitors is regulated by the BTB/POZ domain transcription factor Miz-1.

T cells originate from early T lineage precursors that have entered the thymus and differentiate through well-defined steps. Mice deficient for the BTB/POZ domain of zinc finger protein-1 (Miz-1) almost entirely lack early T lineage precursors and have a CD4(-)CD8(-) to CD4(+)CD8(+) block causing a strong reduction in thymic cellularity. Miz-1(ΔPOZ) pro-T cells cannot differentiate in vitro and are unable to relay signals from the interleukin-7R (IL-7R). Both STAT5 phosphorylation and Bcl-2 up-regulation are perturbed. The high expression levels of SOCS1 found in Miz-1(ΔPOZ) cells probably cause these alterations. Moreover, Miz-1 can bind to the SOCS1 promoter, suggesting that Miz-1 deficiency causes a deregulation of SOCS1. Transgenic overexpression of Bcl-2 or inhibition of SOCS1 restored pro-T cell numbers and their ability to differentiate, supporting the hypothesis that Miz-1 is required for the regulation of the IL-7/IL-7R/STAT5/Bcl-2 signaling pathway by monitoring the expression levels of SOCS1.

Pubmed ID: 21258009

Authors

  • Saba I
  • Kosan C
  • Vassen L
  • Möröy T

Journal

Blood

Publication Data

March 24, 2011

Associated Grants

  • Agency: Canadian Institutes of Health Research, Id: 84526

Mesh Terms

  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Cell Survival
  • Cells, Cultured
  • Gene Expression Regulation
  • Kruppel-Like Transcription Factors
  • Lymphoid Progenitor Cells
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Protein Structure, Tertiary
  • Receptors, Interleukin-7
  • Suppressor of Cytokine Signaling Proteins
  • T-Lymphocytes
  • Transcription Factors
  • Zinc Fingers