Protein dislocation from the endoplasmic reticulum--pulling out the suspect.
Proteins that fail to fold properly as well as constitutive or regulated short-lived proteins of the endoplasmic reticulum are subjected to proteolysis by cytosolic 26S proteasomes. This process is known as endoplasmic reticulum-associated protein degradation. In order to become accessible to the proteasome of this system substrates must first be retrogradely transported from the endoplasmic reticulum into the cytosol, in a process termed dislocation. This export step seems to be accompanied by polyubiquitination of such molecules. Surprisingly, protein dislocation from the endoplasmic reticulum seems to require at least some components that mediate import into this compartment. However, protein import and export display differences in the mechanism that provides the driving force and ensures directionality. Of special interest is the cytoplasmic Cdc48p/Npl4p/Ufd1p complex, which is required for the degradation of various endoplasmic reticulum-associated protein degradation substrates and seems to function in a step after polyubiquitination but before proteasomal digestion. In this review, we will summarize our knowledge on protein export during endoplasmic reticulum-associated protein degradation and discuss the possible function of certain components involved in this process.
Jarosch
Ernst
E
Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Str. 10, 13092 Berlin, Germany.
Geiss-Friedlander
Ruth
R
Meusser
Birgit
B
Walter
Jan
J
Sommer
Thomas
T
D000251:Adenosine Triphosphatases; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D021381:Protein Transport; D000069816:SEC Translocation Channels; D025801:Ubiquitin / Q000378:metabolism; D000074405:Valosin Containing Protein
D018797:Cell Cycle Proteins; D008565:Membrane Proteins; D000069816:SEC Translocation Channels; D025801:Ubiquitin; D000251:Adenosine Triphosphatases; D000074405:Valosin Containing Protein