Wong, W.F. and Kurokawa, M. and Satake, M. and Kohu, K. (2011) Down-regulation of Runx1 Expression by TCR Signal Involves an Autoregulatory Mechanism and Contributes to IL-2 Production. The Journal of Biological Chemistry, 286. pp. 11110-11118. ISSN 0021-9258, DOI https://doi.org/10.1074/jbc.M110.166694.
Full text not available from this repository.Abstract
Runx1 transcription factor plays multiple roles in T cell development, differentiation, and function. However, the regulatory mechanisms and functional significance of high Runx1 protein expression in resting peripheral CD4+ T cells is not well understood. Here, we demonstrate that T-cell receptor (TCR) activation down-regulates distal Runx1 transcription, resulting in a significant reduction of Runx1 protein. Interestingly, this down-regulation of distal Runx1 transcription appears to be mediated through a negative auto-regulatory mechanism, whereby Runx1 protein binds to a Runx consensus site in the distal promoter. Through the use of Runx1-overexpressing cells from transgenic mice, we demonstrate that interference with TCR-mediated Runx1 down-regulation inhibits IL-2 production and proliferation in activated CD4+ T cells. In contrast, using Runx1-deficient cells prepared from targeted mice, we show that the absence of Runx1 in unstimulated CD4+ T cells results in IL-2 derepression. In summary, we propose that high levels of Runx1 in resting CD4+ T cells functions negatively in the regulation of IL-2 transcription, and that TCR activation-mediated down-regulation of Runx1 involves negative auto-regulation of the distal Runx1 promoter and contributes to IL-2 production.
| Item Type: | Article |
|---|---|
| Funders: | UNSPECIFIED |
| Uncontrolled Keywords: | Cytokine; Gene Regulation; Immunology; Interleukin; T-cell Receptor; Transcription Factors; Transcription Promoter; Runx1; T Cell Activation |
| Subjects: | R Medicine |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 13 Mar 2015 01:32 |
| Last Modified: | 13 Mar 2015 01:32 |
| URI: | http://eprints.um.edu.my/id/eprint/13024 |
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