Control of mRNA decay by heat shock ubiquitin proteasome pathway
Control of mRNA decay by heat shock ubiquitin proteasome pathway
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DOI：
10.1126/science.284.5413.499
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发表时间：
1999-04-16
期刊：
影响因子：
56.9
通讯作者：
Schneider, RJ
中科院分区：
文献类型：
--
作者：
Laroia, G;Cuesta, R;Schneider, RJ
细胞因子和原癌基因信使RNA(MRNAs)在3‘非翻译区通过富含AU的元件被迅速降解。快速衰变涉及富含AU的结合蛋白AUF1，它与热休克蛋白hsc70-HSP70、翻译起始因子elF4G和Poly(A)结合蛋白形成络合物。富含Au的mRNA的衰退与AUF1中elF4G的置换、AUF1的泛素化以及蛋白酶体对AUF1的降解有关。热休克诱导HSP70、泛素-蛋白酶体网络的下调或泛素化酶E1的失活都会导致AUF1的HSP70滞留在核周-核中，这三个过程都阻止了富含AU的mRNAs和AUF1蛋白的衰退。这些结果将细胞因子mRNAs的快速降解与泛素-蛋白酶体途径联系起来。
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 elF4G, and poly(A) binding protein. AU-rich mRNA decay is associated with displacement of elF4G 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.