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Laroia, G, Cuesta, R, Brewer, G and Schneider, RJ (1999) Control of mRNA decay by heat shock-ubiquitin-proteasome pathway. Science 284:499-502
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.
3' Untranslated Regions; Carrier Proteins/metabolism; Cell Nucleus/metabolism; Cysteine Endopeptidases/metabolism; Cysteine Proteinase Inhibitors/pharmacology; Cytoplasm/metabolism; Eukaryotic Initiation Factor-4G; Granulocyte-Macrophage Colony-Stimulating Factor/genetics; HSC70 Heat-Shock Proteins; HSP70 Heat-Shock Proteins/metabolism; HeLa Cells; Heat-Shock Response; Heterogeneous-Nuclear Ribonucleoprotein D; Humans; Leupeptins/pharmacology; Multienzyme Complexes/metabolism; Peptide Initiation Factors/metabolism; Poly(A)-Binding Proteins; Proteasome Endopeptidase Complex; Protein Binding; RNA, Messenger/genetics; RNA, Messenger/metabolism; RNA-Binding Proteins/metabolism; Transfection; Ubiquitins/metabolism