Defective activation and survival of T cells lacking the Ets-1 transcription factor
Abstract
The Ets-1 proto-oncogene is a member of the Ets family of eukaryotic transcription factors. Members of this family play important roles in regulating gene expression in response to multiple developmental and mitogenic signals. Ets-1 is preferentially expressed at high levels in B and T cells of adult mice and is regulated during both thymocyte development and T-cell activation. To study the role of Ets-1 in T-cell development and function we have used the RAG-2-/- complementation system and murine embryonic stem (ES) cells containing homozygous deletions in the Ets-1 gene (Ets-1-/-). Ets-1-/(-)-RAG-2-/- chimaeric mice displayed markedly decreased numbers of mature thymocytes and peripheral T cells. Ets-1-/- T cells expressed normal levels of CD3 and T-cell antigen receptor (TCR)-alpha/beta. However, they displayed a severe proliferative defect in response to multiple activational signals and demonstrated increased rates of spontaneous apoptosis in vitro. These findings demonstrate that Ets-1 is required for the normal survival and activation of murine T cells.
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The three regulons active in all subsets were governed by TFs Bclaf1, Elf1, and Ets1, previously shown as key regulators of T cell homeostasis and activation.
“The three regulons that were active in all subsets were governed by the TFs Bclaf1, Elf1, and Ets1, previously shown as key regulators of T cell homeostasis and activation [fig. S6A; (44, 45)].”
From Aging promotes reorganization of the CD4 T cell landscape toward extreme regulatory and effector phenotypes (2019) · cites this paper as [45]
Genomic studies are consistent with genetics experiments in which ETS1-deleted mice have T-cell activation defects.
“These genomic studies are consistent with genetics experiments in which mice with a deletion of ETS1 have defects in T-cell activation (159).”
From Genomic and biochemical insights into the specificity of ETS transcription factors (2011) · cites this paper as [159]
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- Authors
- Muthusamy, N., Barton, K., & Leiden, J. M.
- Affiliations
- University of Chicago (US)
- ORCID
- Muthusamy, Natarajan
- Venue
- Nature
- Published
- 1995-10
- Volume
- 377
- Issue
- 6550
- Pages
- 639-642
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2077452186
- Cited by
- 330
- References
- 24
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 14 · 2023: 5 · 2022: 9 · 2021: 7 · 2020: 8 · 2019: 10 · 2018: 3 · 2017: 9 · 2016: 6 · 2015: 9 · 2014: 4 · 2013: 5 · 2012: 7
- FWCI
- 7.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- ETS1, T cell activation, T cell survival, T cell development, T cell proliferation, apoptosis, transcription factors, T cell receptor, embryonic stem cells
- MeSH terms
- Proto-Oncogene Mas, Animals, Cell Division, Cell Line, Cell Survival, Chimera, DNA-Binding Proteins, Lymphocyte Activation, Proteins, Proto-Oncogene Proteins, Spleen, Stem Cells, T-Lymphocytes, Transcription Factors, CD4 Antigens, Receptors, Antigen, T-Cell, alpha-beta, CD8 Antigens, Apoptosis, CD3 Complex, Sequence Deletion, Proto-Oncogene Proteins c-ets, Proto-Oncogene Protein c-ets-1, Mice
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