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    Science. 1999 Apr 16;284(5413):499-502.

    Control of mRNA decay by heat shock-ubiquitin-proteasome pathway.

    Laroia G, Cuesta R, Brewer G, Schneider RJ.

    Source

    Department of Microbiology and Biochemistry, New York University School of Medicine, New York, NY 10016, USA.

    Abstract

    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.

    PMID:
    10205060
    [PubMed - indexed for MEDLINE]
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