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Science 14 August 1998:
Vol. 281. no. 5379, pp. 1001 - 1005
DOI: 10.1126/science.281.5379.1001
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Reports

Feedback Inhibition of Macrophage Tumor Necrosis Factor-alpha Production by Tristetraprolin

Ester Carballo, * Wi S. Lai, * Perry J. Blackshear dagger

Tumor necrosis factor-alpha (TNF-alpha ) is a major mediator of both acute and chronic inflammatory responses in many diseases. Tristetraprolin (TTP), the prototype of a class of Cys-Cys-Cys-His (CCCH) zinc finger proteins, inhibited TNF-alpha production from macrophages by destabilizing its messenger RNA. This effect appeared to result from direct TTP binding to the AU-rich element of the TNF-alpha messenger RNA. TTP is a cytosolic protein in these cells, and its biosynthesis was induced by the same agents that stimulate TNF-alpha production, including TNF-alpha itself. These findings identify TTP as a component of a negative feedback loop that interferes with TNF-alpha production by destabilizing its messenger RNA. This pathway represents a potential target for anti-TNF-alpha therapies.

Office of Clinical Research and Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA, and Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.
*   These authors contributed equally to this report.

dagger    To whom correspondence should be addressed. E-mail: black009{at}niehs.nih.gov

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   Abstract »    Full Text »    PDF »
Functionally Independent AU-rich Sequence Motifs Regulate KC (CXCL1) mRNA.
M. Novotny, S. Datta, R. Biswas, and T. Hamilton (2005)
J. Biol. Chem. 280, 30166-30174
   Abstract »    Full Text »    PDF »
Zfp36l3, a Rodent X Chromosome Gene Encoding a Placenta-Specific Member of the Tristetraprolin Family of CCCH Tandem Zinc Finger Proteins.
P. J. Blackshear, R. S. Phillips, S. Ghosh, S. V.B. Ramos, E. K. Richfield, and W. S. Lai (2005)
Biol Reprod 73, 297-307
   Abstract »    Full Text »    PDF »
Structure/Function Analysis of Tristetraprolin (TTP): p38 Stress-Activated Protein Kinase and Lipopolysaccharide Stimulation Do Not Alter TTP Function.
W. F. C. Rigby, K. Roy, J. Collins, S. Rigby, J. E. Connolly, D. B. Bloch, and S. A. Brooks (2005)
J. Immunol. 174, 7883-7893
   Abstract »    Full Text »    PDF »
Tristetraprolin Regulates the Expression of the Human Inducible Nitric-Oxide Synthase Gene.
M. Fechir, K. Linker, A. Pautz, T. Hubrich, U. Forstermann, F. Rodriguez-Pascual, and H. Kleinert (2005)
Mol. Pharmacol. 67, 2148-2161
   Abstract »    Full Text »    PDF »
Identification of Direct Genomic Targets Downstream of the Nuclear Factor-{kappa}B Transcription Factor Mediating Tumor Necrosis Factor Signaling.
B. Tian, D. E. Nowak, M. Jamaluddin, S. Wang, and A. R. Brasier (2005)
J. Biol. Chem. 280, 17435-17448
   Abstract »    Full Text »    PDF »
Herpes Simplex Virus Infection Stabilizes Cellular IEX-1 mRNA.
W.-L. Hsu, H. A. Saffran, and J. R. Smiley (2005)
J. Virol. 79, 4090-4098
   Abstract »    Full Text »    PDF »
Fragile X-related Protein FXR1P Regulates Proinflammatory Cytokine Tumor Necrosis Factor Expression at the Post-transcriptional Level.
J. Garnon, C. Lachance, S. Di Marco, Z. Hel, D. Marion, M. C. Ruiz, M. M. Newkirk, E. W. Khandjian, and D. Radzioch (2005)
J. Biol. Chem. 280, 5750-5763
   Abstract »    Full Text »    PDF »
Tristetraprolin Down-Regulates IL-2 Gene Expression through AU-Rich Element-Mediated mRNA Decay.
R. L. Ogilvie, M. Abelson, H. H. Hau, I. Vlasova, P. J. Blackshear, and P. R. Bohjanen (2005)
J. Immunol. 174, 953-961
   Abstract »    Full Text »    PDF »
The Zinc Finger Antiviral Protein Directly Binds to Specific Viral mRNAs through the CCCH Zinc Finger Motifs.
X. Guo, J.-W. N. Carroll, M. R. MacDonald, S. P. Goff, and G. Gao (2004)
J. Virol. 78, 12781-12787
   Abstract »    Full Text »    PDF »
Prostaglandin A2-mediated Stabilization of p21 mRNA through an ERK-dependent Pathway Requiring the RNA-binding Protein HuR.
X. Yang, W. Wang, J. Fan, A. Lal, D. Yang, H. Cheng, and M. Gorospe (2004)
J. Biol. Chem. 279, 49298-49306
   Abstract »    Full Text »    PDF »
AMP-activated Protein Kinase-regulated Phosphorylation and Acetylation of Importin {alpha}1: INVOLVEMENT IN THE NUCLEAR IMPORT OF RNA-BINDING PROTEIN HuR.
W. Wang, X. Yang, T. Kawai, I. L. de Silanes, K. Mazan-Mamczarz, P. Chen, Y. M. Chook, C. Quensel, M. Kohler, and M. Gorospe (2004)
J. Biol. Chem. 279, 48376-48388
   Abstract »    Full Text »    PDF »
Pressure Overload Induces Cardiac Dysfunction and Dilation in Signal Transducer and Activator of Transcription 6-Deficient Mice.
S. Hikoso, O. Yamaguchi, Y. Higuchi, S. Hirotani, T. Takeda, K. Kashiwase, T. Watanabe, M. Taniike, I. Tsujimoto, M. Asahi, et al. (2004)
Circulation 110, 2631-2637
   Abstract »    Full Text »    PDF »
The CCCH tandem zinc-finger protein Zfp36l2 is crucial for female fertility and early embryonic development.
S. B. V. Ramos, D. J. Stumpo, E. A. Kennington, R. S. Phillips, C. B. Bock, F. Ribeiro-Neto, and P. J. Blackshear (2004)
Development 131, 4883-4893
   Abstract »    Full Text »    PDF »
Herpes Simplex Virus 1 Induces Cytoplasmic Accumulation of TIA-1/TIAR and both Synthesis and Cytoplasmic Accumulation of Tristetraprolin, Two Cellular Proteins That Bind and Destabilize AU-Rich RNAs.
A. Esclatine, B. Taddeo, and B. Roizman (2004)
J. Virol. 78, 8582-8592
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Toll IL-1 Receptors Differ in Their Ability to Promote the Stabilization of Adenosine and Uridine-Rich Elements Containing mRNA.
S. Datta, M. Novotny, X. Li, J. Tebo, and T. A. Hamilton (2004)
J. Immunol. 173, 2755-2761
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The Stability of Tristetraprolin mRNA Is Regulated by Mitogen-activated Protein Kinase p38 and by Tristetraprolin Itself.
C. R. Tchen, M. Brook, J. Saklatvala, and A. R. Clark (2004)
J. Biol. Chem. 279, 32393-32400
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Chorioallantoic Fusion Defects and Embryonic Lethality Resulting from Disruption of Zfp36L1, a Gene Encoding a CCCH Tandem Zinc Finger Protein of the Tristetraprolin Family.
D. J. Stumpo, N. A. Byrd, R. S. Phillips, S. Ghosh, R. R. Maronpot, T. Castranio, E. N. Meyers, Y. Mishina, and P. J. Blackshear (2004)
Mol. Cell. Biol. 24, 6445-6455
   Abstract »    Full Text »    PDF »


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