AU-rich elements (AREs) are critical regulators of cytokine and proto-oncogene messenger RNAs, preventing aberrant inflammation and uncontrolled growth. The protein Nup475 (also known at tristetraprolin and TIS11) is the prototype of a family of ARE-binding proteins with a common structural motif, the Cys3His domain, which we have proven has a novel structure distinct from the classical zinc finger. Nup475 destabilizes mRNAs by deadenylation of the polyA tail, as well as with effects on transcriptional activation and to promote apoptosis. This proposal will define determinants of Nup475 binding and potential mechanisms for its action, including the role of this protein in a mouse model of inflammatory bowel disease.
| Rowlett, Robert M; Chrestensen, Carol A; Schroeder, Melanie J et al. (2008) Inhibition of tristetraprolin deadenylation by poly(A) binding protein. Am J Physiol Gastrointest Liver Physiol 295:G421-30 |
| Rowlett, Robert M; Chrestensen, Carol A; Nyce, Mark et al. (2008) MNK kinases regulate multiple TLR pathways and innate proinflammatory cytokines in macrophages. Am J Physiol Gastrointest Liver Physiol 294:G452-9 |
| Chrestensen, Carol A; Schroeder, Melanie J; Shabanowitz, Jeffrey et al. (2004) MAPKAP kinase 2 phosphorylates tristetraprolin on in vivo sites including Ser178, a site required for 14-3-3 binding. J Biol Chem 279:10176-84 |
| Worthington, Mark T; Pelo, Jared W; Sachedina, Muhammadreza A et al. (2002) RNA binding properties of the AU-rich element-binding recombinant Nup475/TIS11/tristetraprolin protein. J Biol Chem 277:48558-64 |
