Protein quality control: U-box-containing E3 ubiquitin ligases join the fold.
Molecular chaperones act with folding co-chaperones to suppress protein aggregation and refold stress damaged proteins. However, it is not clear how slowly folding or misfolded polypeptides are targeted for proteasomal degradation. Generally, selection of proteins for degradation is mediated by E3 ubiquitin ligases of the mechanistically distinct HECT and RING domain sub-types. Recent studies suggest that the U-box protein family represents a third class of E3 enzymes. CHIP, a U-box-containing protein, is a degradatory co-chaperone of heat-shock protein 70 (Hsp70) and Hsp90 that facilitates the polyubiquitination of chaperone substrates. These data indicate a model for protein quality control in which the interaction of Hsp70 and Hsp90 with co-chaperones that have either folding or degradatory activity helps to determine the fate of non-native cellular proteins.
Dept of Cell and Developmental Biology and The UNC-Cystic Fibrosis Center, 524 Taylor Hall, University of North Carolina, Chapel Hill, NC 27599-7060, USA. dmcyr@med.unc.edu
Douglas M
DM
Cyr
Jörg
J
Höhfeld
Cam
C
Patterson
D003546:Cysteine Endopeptidases / Q000378:metabolism; D008025:Ligases / Q000737:chemistry / Q000378:metabolism*; D046911:Macromolecular Substances; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D005810:Multigene Family; D046988:Proteasome Endopeptidase Complex; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000502:physiology; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
D046911:Macromolecular Substances; D018832:Molecular Chaperones; D009097:Multienzyme Complexes; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D008025:Ligases