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

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Science  16 Apr 1999:
Vol. 284, Issue 5413, pp. 499-502
DOI: 10.1126/science.284.5413.499

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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.

  • * To whom correspondence should be addressed. E-mail: schner01{at}mcrcr6.med.nyu.edu

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