ArticlePloS one2013
Zfat-deficiency results in a loss of CD3ζ phosphorylation with dysregulation of ERK and Egr activities leading to impaired positive selection.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 14 citations in OpenAlex.
- p97-mediated proteostasis is a checkpoint for late-stage thymocyte positive selection.Cellular & molecular immunology · 2026Article
- The transcriptional regulator Zfat is essential for maintenance and differentiation of the adipocytes.Journal of cellular biochemistry · 2021Article
- Genetic Factors in Antiphospholipid Syndrome: Preliminary Experience with Whole Exome Sequencing.International journal of molecular sciences · 2020Review
- ZFAT binds to centromeres to control noncoding RNA transcription through the KAT2B-H4K8ac-BRD4 axis.Nucleic acids research · 2020Article
- Zfat expression in ZsGreen reporter gene knock‑in mice: Implications for a novel function of Zfat in definitive erythropoiesis.International journal of molecular medicine · 2018Article
- ROS-induced cleavage of NHLRC2 by caspase-8 leads to apoptotic cell death in the HCT116 human colon cancer cell line.Cell death & disease · 2017Article
- The Nuclear Zinc Finger Protein Zfat Maintains FoxO1 Protein Levels in Peripheral T Cells by Regulating the Activities of Autophagy and the Akt Signaling Pathway.The Journal of biological chemistry · 2016Article
- CBAP promotes thymocyte negative selection by facilitating T-cell receptor proximal signaling.Cell death & disease · 2014Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human ZFAT gene was originally identified as a susceptibility gene for autoimmune thyroid disease. Mouse Zfat is a critical transcriptional regulator for primitive hematopoiesis and required for peripheral T cell homeostasis. However, its physiological roles in T cell development remain poorly understood. Here, we generated Zfat (f/f)-LckCre mice and demonstrated that T cell-specific Zfat-deletion in Zfat (f/f)-LckCre mice resulted in a reduction in the number of CD4(+)CD8(+)double-positive (DP) cells, CD4(+)single positive cells and CD8(+)single positive cells. Indeed, in Zfat (f/f)-LckCre DP cells, positive selection was severely impaired. Defects of positive selection in Zfat-deficient thymocytes were not restored in the presence of the exogenous TCR by using TCR-transgenic mice. Furthermore, Zfat-deficient DP cells showed a loss of CD3ζ phosphorylation in response to T cell antigen receptor (TCR)-stimulation concomitant with dysregulation of extracellular signal-related kinase (ERK) and early growth response protein (Egr) activities. These results demonstrate that Zfat is required for proper regulation of the TCR-proximal signalings, and is a crucial molecule for positive selection through ERK and Egr activities, thus suggesting that a full understanding of the precise molecular mechanisms of Zfat will provide deeper insight into T cell development and immune regulation.
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