| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
Departments of
*
Medicine and
Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756;
Veterans Affairs Medical Center, White River Junction, VT 05009; and
Baylor Institute for Immunology Research, Dallas, TX 75204
Tristetraprolin (TTP) is a regulator of TNF-
mRNA stability and is the only trans-acting factor shown to be capable of regulating AU-rich element-dependent mRNA turnover at the level of the intact animal. Using the THP-1 myelomonocytic cell line, we demonstrated for the first time that TTP is encoded by an mRNA with a short half-life under resting conditions. Using pharmacologic inhibitors of the mitogen-activated protein kinase pathways, we show that the induction of TTP by LPS activation is mediated through changes in transcription, mRNA stability, and translation. A coordinate increase in both TTP and TNF- mRNA stability occurs within 15 min of LPS treatment, but is transduced through different mitogen-activated protein kinase pathways. This regulation of TTP and TNF- mRNA stability is associated with the finding that TTP binds these mRNA under both resting and LPS-activated conditions in vivo. Finally, we demonstrate that TTP can regulate reporter gene expression in a TTP 3' untranslated region-dependent manner and identify three distinct AU-rich elements necessary to mediate this effect. Thus, TTP regulates its own expression in a manner identical to that seen with the TNF- 3' untranslated region, indicating that this autoregulation is mediated at the level of mRNA stability. In this manner, TTP is able to limit the production of its own proteins as well as that of TNF- and thus limit the response of the cell to LPS.
Related articles in The JI:
This article has been cited by other articles:
|
|
 |
|
  J. Emmons, W.H. D. Townley-Tilson, K. M. Deleault, S. J. Skinner, R. H. Gross, M. L. Whitfield, and S. A. Brooks Identification of TTP mRNA targets in human dendritic cells reveals TTP as a critical regulator of dendritic cell maturation RNA, May 1, 2008; 14(5): 888 - 902. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Ciais, M. T. Bohnsack, and D. Tollervey The mRNA encoding the yeast ARE-binding protein Cth2 is generated by a novel 3' processing pathway Nucleic Acids Res., May 1, 2008; 36(9): 3075 - 3084. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Stoecklin, S. A. Tenenbaum, T. Mayo, S. V. Chittur, A. D. George, T. E. Baroni, P. J. Blackshear, and P. Anderson Genome-wide Analysis Identifies Interleukin-10 mRNA as Target of Tristetraprolin J. Biol. Chem., April 25, 2008; 283(17): 11689 - 11699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Skinner, K. M. Deleault, R. Fecteau, and S. A. Brooks Extracellular Signal-regulated Kinase Regulation of Tumor Necrosis Factor-{alpha} mRNA Nucleocytoplasmic Transport Requires TAP-NxT1 Binding and the AU-rich Element J. Biol. Chem., February 8, 2008; 283(6): 3191 - 3199. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Winzen, B. K. Thakur, O. Dittrich-Breiholz, M. Shah, N. Redich, S. Dhamija, M. Kracht, and H. Holtmann Functional Analysis of KSRP Interaction with the AU-Rich Element of Interleukin-8 and Identification of Inflammatory mRNA Targets Mol. Cell. Biol., December 1, 2007; 27(23): 8388 - 8400. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Frasca, A. M. Landin, J. P. Alvarez, P. J. Blackshear, R. L. Riley, and B. B. Blomberg Tristetraprolin, a Negative Regulator of mRNA Stability, Is Increased in Old B Cells and Is Involved in the Degradation of E47 mRNA J. Immunol., July 15, 2007; 179(2): 918 - 927. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. S. A. Khabar Rapid transit in the immune cells: the role of mRNA turnover regulation J. Leukoc. Biol., June 1, 2007; 81(6): 1335 - 1344. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Smoak and J. A. Cidlowski Glucocorticoids Regulate Tristetraprolin Synthesis and Posttranscriptionally Regulate Tumor Necrosis Factor Alpha Inflammatory Signaling Mol. Cell. Biol., December 1, 2006; 26(23): 9126 - 9135. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Sauer, B. Schaljo, C. Vogl, I. Gattermeier, T. Kolbe, M. Muller, P. J. Blackshear, and P. Kovarik Interferons limit inflammatory responses by induction of tristetraprolin Blood, June 15, 2006; 107(12): 4790 - 4797. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wang, J. Zhang, S. Theel, J. J. Barb, P. J. Munson, and R. L. Danner Nitric oxide activation of Erk1/2 regulates the stability and translation of mRNA transcripts containing CU-rich elements Nucleic Acids Res., June 6, 2006; 34(10): 3044 - 3056. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Hitti, T. Iakovleva, M. Brook, S. Deppenmeier, A. D. Gruber, D. Radzioch, A. R. Clark, P. J. Blackshear, A. Kotlyarov, and M. Gaestel Mitogen-activated protein kinase-activated protein kinase 2 regulates tumor necrosis factor mRNA stability and translation mainly by altering tristetraprolin expression, stability, and binding to adenine/uridine-rich element. Mol. Cell. Biol., March 1, 2006; 26(6): 2399 - 2407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. F. C. Rigby, K. Roy, J. Collins, S. Rigby, J. E. Connolly, D. B. Bloch, and S. A. Brooks Structure/Function Analysis of Tristetraprolin (TTP): p38 Stress-Activated Protein Kinase and Lipopolysaccharide Stimulation Do Not Alter TTP Function J. Immunol., June 15, 2005; 174(12): 7883 - 7893. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Esclatine, B. Taddeo, and B. Roizman The UL41 protein of herpes simplex virus mediates selective stabilization or degradation of cellular mRNAs PNAS, December 28, 2004; 101(52): 18165 - 18170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Yang, W. Wang, J. Fan, A. Lal, D. Yang, H. Cheng, and M. Gorospe Prostaglandin A2-mediated Stabilization of p21 mRNA through an ERK-dependent Pathway Requiring the RNA-binding Protein HuR J. Biol. Chem., November 19, 2004; 279(47): 49298 - 49306. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
