title: Degradation of unassembled Vph1p reveals novel aspects of the yeast ER quality control system.
abstract: The endoplasmic reticulum quality control (ERQC) system retains and degrades soluble and membrane proteins that misfold or fail to assemble. Vph1p is the 100 kDa membrane subunit of the yeast Saccharomyces cerevisiae V-ATPase, which together with other subunits, assembles into the V-ATPase in the ER, requiring the ER resident protein Vma22p. In vma22Delta cells, Vph1p remains an integral membrane protein with wild-type topology in the ER membrane before undergoing a rapid and concerted degradation requiring neither vacuolar proteases nor transport to the Golgi. Failure to assemble targets Vph1p for degradation in a process involving ubiquitylation, the proteasome and cytosolic but not ER lumenal chaperones. Vph1p appears to possess the traits of a 'classical' ERQC substrate, yet novel characteristics are involved in its degradation: (i) UBC genes other than UBC6 and UBC7 are involved and (ii) components of the ERQC system identified to date (Der1p, Hrd1p/Der3p and Hrd3p) are not required. These data suggest that other ERQC components must exist to effect the degradation of Vph1p, perhaps comprising an alternative pathway.
authors.affiliation: Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO 64110, USA.
authors.forename: K
authors.initials: K
authors.lastname: Hill
authors.forename: A A
authors.initials: AA
authors.lastname: Cooper
mesh_terms: D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004734:Energy Metabolism; D005656:Fungal Proteins / Q000378:metabolism; D005800:Genes, Fungal; D007425:Intracellular Membranes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011786:Quality Control; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D013379:Substrate Specificity; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases
chemical_list: C098515:DER1 protein, S cerevisiae; D005656:Fungal Proteins; C104622:HRD3 protein, S cerevisiae; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; C095635:VMA22 protein, S cerevisiae; C104621:HRD1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D025262:Vacuolar Proton-Translocating ATPases; D006180:Proton-Translocating ATPases