The p38 MAPK pathway is involved in the IL-2 induction of TNF-beta gene via the EBS element.
As an important cytokine of the immune system, interleukin-2 (IL-2) can induce the expression of various genes, one of which is the tumor necrosis factor-beta (TNF-beta). However, the induction mechanism of TNF-beta remains to be fully explored. We have previously shown JAK-STAT pathway mediates TNF-beta gene induction upon IL-2 stimulation through an upstream -200GAS element. In this study, we further demonstrated that there is another essential -130EBS element in TNF-beta gene promoter region. Using IL-2-dependent cell line BAF/BO3beta, we found that this -130EBS element can form a specific complex with nuclear protein, which contained a novel ETS transcription factor. Furthermore, using kinase inhibitors, we revealed that p38 MAP kinase is involved in the formation of -130EBS-protein complex and the subsequent transcriptional activation of TNF-beta gene in response to IL-2 stimulation. Taken together, our results suggested that the complicated IL-2 induction of TNF-beta gene expression requires not only the activation of JAK-STAT pathway on the -200GAS element, but also the cooperation of another signal pathway on the -130EBS element.
Xu
W
W
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China.
Yan
M
M
Lu
L
L
Sun
L
L
Theze
J
J
Zheng
Z
Z
Liu
X
X
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007376:Interleukin-2 / Q000494:pharmacology*; D008233:Lymphotoxin-alpha / Q000235:genetics*; D046911:Macromolecular Substances; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism; D015533:Transcriptional Activation; D048051:p38 Mitogen-Activated Protein Kinases
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D008233:Lymphotoxin-alpha; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D014157:Transcription Factors; D004247:DNA; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases