Methotrexate Inhibits Proteolysis of Dihydrofolate Reductase by the N-end Rule Pathway

摘要: Abstract The N-end rule relates the in vivo half-life of a protein to identity its N-terminal residue. In eukaryotes, pathway is ubiquitin-dependent, proteasome-based system that targets and processively degrades proteins bearing certain residues. Arg-DHFR, modified dihydrofolate reductase an arginine (destabilizing residue rule), short lived ATP-supplemented reticulocyte extract. It shown here methotrexate, which folic acid analog high affinity ligand DHFR, inhibits degradation but not ubiquitination Arg-DHFR by pathway. other substrates affected methotrexate. We discuss implications these results for mechanism proteasome-mediated degradation.