Control of mRNA decay by heat shock-ubiquitin-proteasome pathway.
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.
Mesh Terms:
3' Untranslated Regions, Carrier Proteins, Cell Nucleus, Cysteine Endopeptidases, Cysteine Proteinase Inhibitors, Cytoplasm, Eukaryotic Initiation Factor-4G, Granulocyte-Macrophage Colony-Stimulating Factor, HSC70 Heat-Shock Proteins, HSP70 Heat-Shock Proteins, Heat-Shock Response, Hela Cells, Heterogeneous-Nuclear Ribonucleoprotein D, Humans, Leupeptins, Multienzyme Complexes, Peptide Initiation Factors, Poly(A)-Binding Proteins, Proteasome Endopeptidase Complex, Protein Binding, RNA, Messenger, RNA-Binding Proteins, Transfection, Ubiquitins
3' Untranslated Regions, Carrier Proteins, Cell Nucleus, Cysteine Endopeptidases, Cysteine Proteinase Inhibitors, Cytoplasm, Eukaryotic Initiation Factor-4G, Granulocyte-Macrophage Colony-Stimulating Factor, HSC70 Heat-Shock Proteins, HSP70 Heat-Shock Proteins, Heat-Shock Response, Hela Cells, Heterogeneous-Nuclear Ribonucleoprotein D, Humans, Leupeptins, Multienzyme Complexes, Peptide Initiation Factors, Poly(A)-Binding Proteins, Proteasome Endopeptidase Complex, Protein Binding, RNA, Messenger, RNA-Binding Proteins, Transfection, Ubiquitins
Science
Date: Apr. 16, 1999
PubMed ID: 10205060
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