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Early growth response 1 and NF-ATc1 act in concert to promote thymocyte development beyond the beta-selection checkpoint.

Publication ,  Journal Article
Koltsova, EK; Ciofani, M; Benezra, R; Miyazaki, T; Clipstone, N; Zúñiga-Pflücker, JC; Wiest, DL
Published in: J Immunol
October 1, 2007

Development of immature T cell precursors beyond the beta-selection checkpoint is regulated by signals transduced by the pre-TCR complex. The pre-TCR-induced differentiation program is orchestrated by a network of transcription factors that serve to integrate this signaling information. Among these transcription factors are those of the early growth response (Egr) and NF-AT families. In this study, we demonstrate that Egr1 and NF-ATc1 act together to promote development of T cell precursors beyond the beta-selection checkpoint to the CD8 immature single-positive and CD4+ CD8+ double-positive stages. Moreover, we find that Egr1 and NF-AT cooperatively induce the expression of inhibitor of DNA binding 3 (Id3), a regulatory factor known to play an important role in positive selection of thymocytes, but not previously demonstrated to be required for beta-selection. Importantly, we show in this study that Id3 deficiency abrogates the ability of ectopically expressed Egr1 to promote traversal of the beta-selection checkpoint. Id3 is presumably essential for traversal of the beta-selection checkpoint in this context because of the inability of other inhibitor of DNA binding family members to compensate, since transgenic Egr1 does not induce expression of inhibitor of DNA binding 1 (Id1) or 2 (Id2). Taken together, these data demonstrate that Id3 is a cooperatively induced target that is important for Egr-mediated promotion of development beyond the beta-selection checkpoint. Moreover, these data indicate that the ERK and calcium signaling pathways may converge during beta-selection through the concerted action of Egr1 and NF-ATc1, respectively.

Duke Scholars

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

October 1, 2007

Volume

179

Issue

7

Start / End Page

4694 / 4703

Location

United States

Related Subject Headings

  • Thymus Gland
  • T-Lymphocytes
  • Signal Transduction
  • NFATC Transcription Factors
  • Mice, Transgenic
  • Mice
  • Inhibitor of Differentiation Proteins
  • Immunology
  • Humans
  • Gene Expression Regulation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Koltsova, E. K., Ciofani, M., Benezra, R., Miyazaki, T., Clipstone, N., Zúñiga-Pflücker, J. C., & Wiest, D. L. (2007). Early growth response 1 and NF-ATc1 act in concert to promote thymocyte development beyond the beta-selection checkpoint. J Immunol, 179(7), 4694–4703. https://doi.org/10.4049/jimmunol.179.7.4694
Koltsova, Ekaterina K., Maria Ciofani, Robert Benezra, Toru Miyazaki, Neil Clipstone, Juan Carlos Zúñiga-Pflücker, and David L. Wiest. “Early growth response 1 and NF-ATc1 act in concert to promote thymocyte development beyond the beta-selection checkpoint.J Immunol 179, no. 7 (October 1, 2007): 4694–4703. https://doi.org/10.4049/jimmunol.179.7.4694.
Koltsova EK, Ciofani M, Benezra R, Miyazaki T, Clipstone N, Zúñiga-Pflücker JC, et al. Early growth response 1 and NF-ATc1 act in concert to promote thymocyte development beyond the beta-selection checkpoint. J Immunol. 2007 Oct 1;179(7):4694–703.
Koltsova, Ekaterina K., et al. “Early growth response 1 and NF-ATc1 act in concert to promote thymocyte development beyond the beta-selection checkpoint.J Immunol, vol. 179, no. 7, Oct. 2007, pp. 4694–703. Pubmed, doi:10.4049/jimmunol.179.7.4694.
Koltsova EK, Ciofani M, Benezra R, Miyazaki T, Clipstone N, Zúñiga-Pflücker JC, Wiest DL. Early growth response 1 and NF-ATc1 act in concert to promote thymocyte development beyond the beta-selection checkpoint. J Immunol. 2007 Oct 1;179(7):4694–4703.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

October 1, 2007

Volume

179

Issue

7

Start / End Page

4694 / 4703

Location

United States

Related Subject Headings

  • Thymus Gland
  • T-Lymphocytes
  • Signal Transduction
  • NFATC Transcription Factors
  • Mice, Transgenic
  • Mice
  • Inhibitor of Differentiation Proteins
  • Immunology
  • Humans
  • Gene Expression Regulation