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dc.contributor.author Blackshear, Perry en_US
dc.date.accessioned 2011-06-21T17:31:30Z
dc.date.available 2011-06-21T17:31:30Z
dc.date.issued 2010 en_US
dc.identifier.citation Kedar,Vishram P.;Darby,Martyn K.;Williams,Jason G.;Blackshear,Perry J.. 2010. Phosphorylation of Human Tristetraprolin in Response to Its Interaction with the CbI Interacting Protein CIN85. Plos One 5(3): A213-A227. en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://hdl.handle.net/10161/4530
dc.description.abstract Background: Tristetraprolin (TTP) is the prototype member of a family of CCCH tandem zinc finger proteins and is considered to be an anti-inflammatory protein in mammals. TTP plays a critical role in the decay of tumor necrosis factor alpha (TNF) mRNA, among others, by binding AU-rich RNA elements in the 3'-untranslated regions of this transcript and promoting its deadenylation and degradation. Methodology/Principal Findings: We used yeast two-hybrid analysis to identify potential protein binding partners for human TTP (hTTP). Various regions of hTTP recovered 31 proteins that fell into 12 categories based on sequence similarities. Among these, the interactions between hTTP and CIN85, cytoplasmic poly (A) binding protein (PABP), nucleolin and heat shock protein 70 were confirmed by co-immunoprecipitation experiments. CIN85 and hTTP co-localized in the cytoplasm of cells as determined by confocal microscopy. CIN85 contains three SH3 domains that specifically bind a unique proline-arginine motif (PXXXPR) found in several CIN85 effectors. We found that the SH3 domains of CIN85 bound to a PXXXPR motif located near the C-terminus of hTTP. Co-expression of CIN85 with hTTP resulted in the increased phosphorylation of hTTP at serine residues in positions 66 and 93, possibly due in part to the demonstrated association of mitogen-activated protein kinase kinase kinase 4 (MEKK4) to both proteins. The presence of CIN85 did not appear to alter hTTP's binding to RNA probes or its stimulated breakdown of TNF mRNA. Conclusions/Significance: These studies describe interactions between hTTP and nucleolin, cytoplasmic PABP, heat shock protein 70 and CIN85; these interactions were initially discovered by two-hybrid analysis, and confirmed by coimmunoprecipitation. We found that CIN85 binding to a C-terminal motif within hTTP led to the increased phosphorylation of hTTP, possibly through enhanced association with MEKK4. The functional consequences to each of the members of this putative complex remain to be determined. en_US
dc.language.iso en_US en_US
dc.publisher PUBLIC LIBRARY SCIENCE en_US
dc.relation.isversionof doi:10.1371/journal.pone.0009588 en_US
dc.subject tumor-necrosis-factor en_US
dc.subject messenger-rna decay en_US
dc.subject zinc-finger proteins en_US
dc.subject growth-factor receptors en_US
dc.subject map kinase pathway en_US
dc.subject au-rich elements en_US
dc.subject down-regulation en_US
dc.subject transcription factor en_US
dc.subject deficiency syndrome en_US
dc.subject signaling en_US
dc.subject pathway en_US
dc.subject biology en_US
dc.subject multidisciplinary sciences en_US
dc.title Phosphorylation of Human Tristetraprolin in Response to Its Interaction with the CbI Interacting Protein CIN85 en_US
dc.title.alternative en_US
dc.description.version Version of Record en_US
duke.date.pubdate 2010-3-8 en_US
duke.description.endpage A227 en_US
duke.description.issue 3 en_US
duke.description.startpage A213 en_US
duke.description.volume 5 en_US
dc.relation.journal Plos One en_US

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