Regulation of Proteasomal Degradation by Modulating Proteasomal Initiation Regions.
Methods for regulating the concentrations of specific cellular proteins are valuable tools for biomedical studies. Artificial regulation of protein degradation by the proteasome is receiving increasing attention. Efficient proteasomal protein degradation requires a degron with two components: a ubiquitin tag that is recognized by the proteasome and a disordered region at which the proteasome engages the substrate and initiates degradation. Here we show that degradation rates can be regulated by modulating the disordered initiation region by the binding of modifier molecules, in vitro and in vivo. These results suggest that artificial modulation of proteasome initiation is a versatile method for conditionally inhibiting the proteasomal degradation of specific proteins.
Frontier Research Core for Life Sciences, University of Toyama , 3190 Gofuku, Toyama-shi, Toyama 930-8555, Japan.
Kazunobu
K
Takahashi
Department of Molecular Biosciences, The University of Texas at Austin , Austin, Texas 78712, United States.|Department of Molecular Biosciences, Northwestern University , Evanston, Illinois 60201, United States.
Andreas
A
Matouschek
Frontier Research Core for Life Sciences, University of Toyama , 3190 Gofuku, Toyama-shi, Toyama 930-8555, Japan.
Tomonao
T
Inobe
D004591:Electrophoresis, Polyacrylamide Gel; D057809:HEK293 Cells; D006801:Humans; D010448:Peptide Initiation Factors / Q000235:genetics* / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D017510:Protein Folding; D059748:Proteolysis; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
D010448:Peptide Initiation Factors; D029701:Saccharomyces cerevisiae Proteins; D046988:Proteasome Endopeptidase Complex