ER-associated degradation in protein quality control and cellular regulation.
The ER-associated degradation (ERAD) pathway directs ubiquitin-mediated degradation of a variety of ER-associated misfolded and normal proteins. Recent studies have delineated the molecular machinery responsible for protein ubiquitination and highlighted mechanistic questions surrounding the recognition, extraction and proteasomal destruction of the diverse array of ERAD substrates. Consideration of separate lines of work on this versatile pathway now indicate that despite its central role as an avenue of cellular quality control, ERAD is also harnessed for feedback regulation of sterol synthesis, and most likely numerous other cellular processes. These studies give ERAD a larger role in cellular function, and imply that cellular quality-control pathways could be widely employed in both natural and pharmaceutical control of individual proteins.
Hampton
Randolph Y
RY
Section of Cell and Developmental Biology, UCSD Division of Biology #0347, Room 2100E, Pacific Hall, La Jolla, CA 92093-0347, USA. rhampton@ucsd.edu
D000251:Adenosine Triphosphatases; D000818:Animals; D002268:Carboxypeptidases / Q000378:metabolism; D043402:Cathepsin A; D018797:Cell Cycle Proteins / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008025:Ligases / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D017510:Protein Folding; D011506:Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013261:Sterols / Q000096:biosynthesis; D014452:Ubiquitins / Q000378:metabolism; D000074405:Valosin Containing Protein
D018797:Cell Cycle Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; D013261:Sterols; D014452:Ubiquitins; D006903:Hydroxymethylglutaryl CoA Reductases; D002268:Carboxypeptidases; C468629:CTSA protein, human; D043402:Cathepsin A; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; C000614177:CDC48 protein, S cerevisiae; D000074405:Valosin Containing Protein; D008025:Ligases