Detecting and measuring cotranslational protein degradation in vivo.
Nascent polypeptides emerging from the ribosome and not yet folded may at least transiently present degradation signals similar to those recognized by the ubiquitin system in misfolded proteins. The ubiquitin sandwich technique was used to detect and measure cotranslational protein degradation in living cells. More than 50 percent of nascent protein molecules bearing an amino-terminal degradation signal can be degraded cotranslationally, never reaching their mature size before their destruction by processive proteolysis. Thus, the folding of nascent proteins, including abnormal ones, may be in kinetic competition with pathways that target these proteins for degradation cotranslationally.
Turner
G C
GC
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Varshavsky
A
A
D003546:Cysteine Endopeptidases / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D008025:Ligases; D009097:Multienzyme Complexes / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D014176:Protein Biosynthesis; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
D005656:Fungal Proteins; D009097:Multienzyme Complexes; D010455:Peptides; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; D013762:Tetrahydrofolate Dehydrogenase; C066066:UBR1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D012321:DNA-Directed RNA Polymerases; D001616:beta-Galactosidase; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D008025:Ligases