The glycoprotein gp48 of murine cytomegalovirusL proteasome-dependent cytosolic dislocation and degradation.
Degradation of misfolded or unassembled proteins that are co-translationally inserted into the endoplasmic reticulum involves the cytosolic proteasome system. Different principles may exist for the export of proteins into the cytosol for proteasomal degradation. Here we studied the degradation pathway of the viral glycoprotein gp48, a type I transmembrane protein, encoded by the m06 gene of murine cytomegalovirus. In cells stably transfected with the cytomegalovirus m06 gene or infected with the virus itself, two populations of gp48 can be distinguished that have different fates. Complexes of gp48 and the major histocompatibility complex (MHC) class I molecule, are transported to the lysosome for degradation. Unassembled gp48 is degraded by the cytosolic proteasome. Proteasomal inhibitors stabilize the unassembled gp48 in its core-glycosylated and membrane-associated form in the endoplasmic reticulum (ER)-Golgi intermediate compartment. This implicates that both endoplasmic reticulum and ER-Golgi intermediate compartment export gp48 and that degradation is coupled to a functional proteasome. Analysis of gp48 mutants revealed that the cytosolic part of gp48 was not responsible for the proteasome-dependent substrate transport out of the ER-Golgi intermediate compartment. Thus an indirect interaction between the proteasome and its substrate has to be discussed.
Bubeck
Anja
A
Max-von-Pettenkofer Institut, Genzentrum, Ludwig-Maximilians-Universität, 81377 München, Germany.
Reusch
Uwe
U
Wagner
Markus
M
Ruppert
Thomas
T
Muranyi
Walter
W
Kloetzel
Peter M
PM
Koszinowski
Ulrich H
UH
D016475:3T3 Cells; D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003586:Cytomegalovirus Infections / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism*; D017931:DNA Primers; D006868:Hydrolysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D021381:Protein Transport; D014759:Viral Envelope Proteins / Q000378:metabolism*
D015853:Cysteine Proteinase Inhibitors; D017931:DNA Primers; D009097:Multienzyme Complexes; C082590:UL4 protein, Human cytomegalovirus; D014759:Viral Envelope Proteins; C067713:lactacystin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine