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.
Laroia
G
G
Department of Microbiology and Biochemistry, New York University School of Medicine, New York, NY 10016, USA.
Cuesta
R
R
Brewer
G
G
Schneider
R J
RJ
D020413:3' Untranslated Regions; D002352:Carrier Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D039603:Eukaryotic Initiation Factor-4G; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006367:HeLa Cells; D018869:Heat-Shock Response; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000378:metabolism*; D010448:Peptide Initiation Factors / Q000378:metabolism; D039102:Poly(A)-Binding Proteins; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014162:Transfection; D014452:Ubiquitins / Q000378:metabolism*
D020413:3' Untranslated Regions; D002352:Carrier Proteins; D015853:Cysteine Proteinase Inhibitors; D039603:Eukaryotic Initiation Factor-4G; C000630986:HNRNPD protein, human; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D007976:Leupeptins; C000715470:MAS1 protein, human; D009097:Multienzyme Complexes; D010448:Peptide Initiation Factors; D039102:Poly(A)-Binding Proteins; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014452:Ubiquitins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde