Tristetraprolin Regulates Interleukin-6 Expression Through p38 MAPK-Dependent Affinity Changes with mRNA 3' Untranslated Region
dc.contributor.author | Zhao, Wenpu | en_US |
dc.contributor.author | Liu, Min | en_US |
dc.contributor.author | D'Silva, Nisha J. | en_US |
dc.contributor.author | Kirkwood, Keith L. | en_US |
dc.date.accessioned | 2012-03-22T17:24:18Z | |
dc.date.available | 2012-03-22T17:24:18Z | |
dc.date.issued | 2011-08-01 | en_US |
dc.identifier.citation | Zhao, Wenpu; Liu, Min; D'Silva, Nisha J.; Kirkwood, Keith L. (2011). "Tristetraprolin Regulates Interleukin-6 Expression Through p38 MAPK-Dependent Affinity Changes with mRNA 3' Untranslated Region." Journal of Interferon & Cytokine Research, 31(8): 629-637. <http://hdl.handle.net/2027.42/90500> | en_US |
dc.identifier.issn | 1079-9907 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/90500 | |
dc.description.abstract | Tristetraprolin (TTP) is a well-characterized, zinc finger-containing, RNA-binding protein. TTP targets tumor necrosis factor alpha for degradation via the 3- untranslated region (3-UTR). Although AU-rich elements (AREs) in the 3-UTR of interleukin-6 (IL-6) mRNA dictate mRNA degradation, the role of TTP in the post-transcriptional regulation of IL-6 gene expression is unclear. Here we used TTP-deficient mice to test the hypothesis that IL-6 expression is influenced by TTP. Genetic and siRNA-mediated knockdown of TTP resulted in increased IL-6 production and overexpression of TTP had the reverse effect. IL-6 and tumor necrosis factor alpha production were elevated after injection of IL-1- in TTP-deficient mice. Further, embryonic fibroblasts from these mice (mouse embryonic fibroblasts) exhibited greater IL-6 mRNA expression and longer half-life than wild-type mouse embryonic fibroblasts. Overexpression of TTP reduced IL-6 3-UTR luciferase reporter activity in an ARE-dependent manner. Proximal and distal regions of the 3-UTR acted synergistically to produce the full repression of TTP. Mutation-based luciferase assays show that ARE2, ARE3, and ARE4 are required for TTP-mediated repression. The constitutively activated p38-MK2 pathway abrogated TTP-mediated repression of IL-6 3-UTR reporter activity. RNA immunoprecipitation assay indicated that the deficiency of p38alpha resulted in the increased affinity of TTP to IL-6 mRNA. Taken together, we propose that TTP downregulates IL-6 gene expression at the post-transcriptional level by targeting ARE elements in the 3-UTR region. | en_US |
dc.publisher | Mary Ann Liebert, Inc., publishers | en_US |
dc.title | Tristetraprolin Regulates Interleukin-6 Expression Through p38 MAPK-Dependent Affinity Changes with mRNA 3' Untranslated Region | en_US |
dc.type | Article | en_US |
dc.subject.hlbsecondlevel | Medicine (General) | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.identifier.pmid | 21457063 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/90500/1/jir-2E2010-2E0154.pdf | |
dc.identifier.doi | 10.1089/jir.2010.0154 | en_US |
dc.identifier.source | Journal of Interferon & Cytokine Research | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.