Repression of interferon-gamma expression in T cells by Prospero-related Homeobox protein
文献类型：期刊论文
| 作者 | Wang, LF; Zhu, JM; Shan, SF; Qin, Y; Kong, YY; Liu, J; Wang, Y; Xie, YH |
| 刊名 | CELL RESEARCH
 |
| 出版日期 | 2008 |
| 卷号 | 18期号:9页码:911-920 |
| 关键词 | Prox1 IFN-gamma T cell activation gene regulation repression PPAR gamma |
| 通讯作者 | Xie, YH (reprint author), Chinese Acad Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.,yhxie@sibs.ac.cn |
| 英文摘要 | Interferon-gamma (IFN-gamma) is a major proinflammatory effector and regulatory cytokine produced by activated T cells and NK cells. IFN-gamma has been shown to play pivotal roles in fundamental immunological processes such as inflammatory reactions, cell-mediated immunity and autoimmunity. A variety of human disorders have now been linked to irregular IFN-gamma expression. In order to achieve proper IFN-gamma-mediated immunological effects, IFN-gamma expression in T cells is subject to both positive and negative regulation. In this study, we report for the first time the negative regulation of IFN-gamma expression by Prospero-related Homeobox (Prox1). In Jurkat T cells and primary human CD4+ T cells, Prox1 expression decreases quickly upon T cell activation, concurrent with a dramatic increase in IFN-gamma expression. Reporter analysis and chromatin immunoprecipitation (ChIP) revealed that Prox1 associates with and inhibits the transcription activity of IFN-gamma promoter in activated Jurkat T cells. Co-immunoprecipitation and GST pull-down assay demonstrated a direct binding between Prox1 and the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR gamma), which is also an IFN-gamma repressor in T cells. By introducing deletions and mutations into Prox1, we show that the repression of IFN-gamma promoter by Prox1 is largely dependent upon the physical interaction between Prox1 and PPAR gamma. Furthermore, PPAR. antagonist treatment removes Prox1 from IFN-gamma promoter and attenuates repression of IFN-gamma expression by Prox1. These findings establish Prox1 as a new negative regulator of IFN-gamma expression in T cells and will aid in the understanding of IFN-gamma transcription regulation mechanisms. |
| 学科主题 | Cell Biology |
| 类目[WOS] | Cell Biology |
| 关键词[WOS] | ACTIVATED RECEPTOR-GAMMA ; IFN-GAMMA ; NATURAL-KILLER ; PROX1 FUNCTION ; NUCLEAR FACTOR ; MESSENGER-RNA ; PROMOTER ; ELEMENTS ; RESPONSES ; GENE |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000259891200003 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1427]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Wang, LF,Zhu, JM,Shan, SF,et al. Repression of interferon-gamma expression in T cells by Prospero-related Homeobox protein[J]. CELL RESEARCH,2008,18(9):911-920. |
| APA | Wang, LF.,Zhu, JM.,Shan, SF.,Qin, Y.,Kong, YY.,...&Xie, YH.(2008).Repression of interferon-gamma expression in T cells by Prospero-related Homeobox protein.CELL RESEARCH,18(9),911-920. |
| MLA | Wang, LF,et al."Repression of interferon-gamma expression in T cells by Prospero-related Homeobox protein".CELL RESEARCH 18.9(2008):911-920. |
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