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Science 16 April 1999:
Vol. 284. no. 5413, pp. 499 - 502
DOI: 10.1126/science.284.5413.499
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Reports

Control of mRNA Decay by Heat Shock-Ubiquitin-Proteasome Pathway

Gaurav Laroia, 1 Rafael Cuesta, 1 Gary Brewer, 2 Robert J. Schneider 1*

Cytokine and proto-oncogene messenger RNAs (mRNAs) are rapidly degraded through AU-rich elements in the 3' untranslated region. Rapid decay involves AU-rich binding protein AUF1, which complexes with heat shock proteins hsc70-hsp70, translation initiation factor eIF4G, and poly(A) binding protein. AU-rich mRNA decay is associated with displacement of eIF4G from AUF1, ubiquitination of AUF1, and degradation of AUF1 by proteasomes. Induction of hsp70 by heat shock, down-regulation of the ubiquitin-proteasome network, or inactivation of ubiquitinating enzyme E1 all result in hsp70 sequestration of AUF1 in the perinucleus-nucleus, and all three processes block decay of AU-rich mRNAs and AUF1 protein. These results link the rapid degradation of cytokine mRNAs to the ubiquitin-proteasome pathway.

1 Department of Microbiology and Biochemistry, New York University School of Medicine, New York, NY 10016, USA.
2 Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
*   To whom correspondence should be addressed. E-mail: schner01{at}mcrcr6.med.nyu.edu

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   Abstract »    Full Text »    PDF »
Highly Selective Actions of HuR in Antagonizing AU-Rich Element-Mediated mRNA Destabilization.
C.-Y. A. Chen, N. Xu, and A.-B. Shyu (2002)
Mol. Cell. Biol. 22, 7268-7278
   Abstract »    Full Text »    PDF »
Lactate Dehydrogenase Is an AU-rich Element-binding Protein That Directly Interacts with AUF1.
P. A. Pioli, B. J. Hamilton, J. E. Connolly, G. Brewer, and W. F. C. Rigby (2002)
J. Biol. Chem. 277, 35738-35745
   Abstract »    Full Text »    PDF »
Gene expression profiling of the aging mouse cardiac myocytes.
N. Bodyak, P. M. Kang, M. Hiromura, I. Sulijoadikusumo, N. Horikoshi, K. Khrapko, and A. Usheva (2002)
Nucleic Acids Res. 30, 3788-3794
   Abstract »    Full Text »    PDF »
Alternate exon insertion controls selective ubiquitination and degradation of different AUF1 protein isoforms.
G. Laroia and R. J. Schneider (2002)
Nucleic Acids Res. 30, 3052-3058
   Abstract »    Full Text »    PDF »
Hyposmotic Stress Induces Cell Growth Arrest via Proteasome Activation and Cyclin/Cyclin-dependent Kinase Degradation.
G.-Z. Tao, L. S. Rott, A. W. Lowe, and M. B. Omary (2002)
J. Biol. Chem. 277, 19295-19303
   Abstract »    Full Text »    PDF »
AMP-Activated Kinase Regulates Cytoplasmic HuR.
W. Wang, J. Fan, X. Yang, S. Furer-Galban, I. Lopez de Silanes, C. von Kobbe, J. Guo, S. N. Georas, F. Foufelle, D. G. Hardie, et al. (2002)
Mol. Cell. Biol. 22, 3425-3436
   Abstract »    Full Text »    PDF »
From the Cover: Characterization of the c-MYC-regulated transcriptome by SAGE: Identification and analysis of c-MYC target genes.
A. Menssen and H. Hermeking (2002)
PNAS 99, 6274-6279
   Abstract »    Full Text »    PDF »
Mass Spectrometric Analysis of the N Terminus of Translational Initiation Factor eIF4G-1 Reveals Novel Isoforms.
C. A. Bradley, J. C. Padovan, T. L. Thompson, C. A. Benoit, B. T. Chait, and R. E. Rhoads (2002)
J. Biol. Chem. 277, 12559-12571
   Abstract »    Full Text »    PDF »
The Ubiquitin-Proteasome Proteolytic Pathway: Destruction for the Sake of Construction.
M. H. Glickman and A. Ciechanover (2002)
Physiol Rev 82, 373-428
   Abstract »    Full Text »    PDF »
Proteasome inhibitors induce heat shock response and increase IL-6 expression in human intestinal epithelial cells.
T. A. Pritts, E. S. Hungness, D. D. Hershko, B. W. Robb, X. Sun, G.-J. Luo, J. E. Fischer, H. R. Wong, and P.-O. Hasselgren (2002)
Am J Physiol Regulatory Integrative Comp Physiol 282, R1016-R1026
   Abstract »    Full Text »    PDF »
Versatile Role for hnRNP D Isoforms in the Differential Regulation of Cytoplasmic mRNA Turnover.
N. Xu, C.-Y. A. Chen, and A.-B. Shyu (2001)
Mol. Cell. Biol. 21, 6960-6971
   Abstract »    Full Text »    PDF »
Structural Remodeling of an A + U-rich RNA Element by Cation or AUF1 Binding.
G. M. Wilson, K. Sutphen, M. Moutafis, S. Sinha, and G. Brewer (2001)
J. Biol. Chem. 276, 38400-38409
   Abstract »    Full Text »    PDF »
Mitogen-Activated Protein Kinase p38 Controls the Expression and Posttranslational Modification of Tristetraprolin, a Regulator of Tumor Necrosis Factor Alpha mRNA Stability.
K. R. Mahtani, M. Brook, J. L. E. Dean, G. Sully, J. Saklatvala, and A. R. Clark (2001)
Mol. Cell. Biol. 21, 6461-6469
   Abstract »    Full Text »    PDF »
Parallel and Independent Regulation of Interleukin-3 mRNA Turnover by Phosphatidylinositol 3-Kinase and p38 Mitogen-Activated Protein Kinase.
X.-F. Ming, G. Stoecklin, M. Lu, R. Looser, and C. Moroni (2001)
Mol. Cell. Biol. 21, 5778-5789
   Abstract »    Full Text »    PDF »
Transcriptional and Post-Transcriptional Alterations of I {kappa}B{alpha} in Active Minimal-Change Nephrotic Syndrome.
D. SAHALI, A. PAWLAK, S. L. GOUVELLO, P. LANG, A. VALANCIUTE, P. REMY, C. LOIRAT, P. NIAUDET, A. BENSMAN, and G. GUELLAEN (2001)
J. Am. Soc. Nephrol. 12, 1648-1658
   Abstract »    Full Text »    PDF »
Unexpected Transcriptional Induction of Monocyte Chemoattractant Protein 1 by Proteasome Inhibition: Involvement of the c-Jun N-Terminal Kinase-Activator Protein 1 Pathway.
K. Nakayama, A. Furusu, Q. Xu, T. Konta, and M. Kitamura (2001)
J. Immunol. 167, 1145-1150
   Abstract »    Full Text »    PDF »
Sodium 4-phenylbutyrate downregulates HSC70 expression by facilitating mRNA degradation.
R. C. Rubenstein and B. M. Lyons (2001)
Am J Physiol Lung Cell Mol Physiol 281, L43-L51
   Abstract »    Full Text »    PDF »
TNF receptor I is required for induction of macrophage heat shock protein 70.
J. K. Heimbach, L. L. Reznikov, C. M. Calkins, T. N. Robinson, C. A. Dinarello, A. H. Harken, and X. Meng (2001)
Am J Physiol Cell Physiol 281, C241-C247
   Abstract »    Full Text »    PDF »
Exposure to febrile temperature modifies endothelial cell response to tumor necrosis factor-{alpha}.
J. D. Hasday, D. Bannerman, S. Sakarya, A. S. Cross, I. S. Singh, D. Howard, B.-E. Drysdale, and S. E. Goldblum (2001)
J Appl Physiol 90, 90-98
   Abstract »    Full Text »    PDF »


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