title: Mutant membrane protein of the budding yeast spindle pole body is targeted to the endoplasmic reticulum degradation pathway.
abstract: Mutation of either the yeast MPS2 or the NDC1 gene leads to identical spindle pole body (SPB) duplication defects: The newly formed SPB is improperly inserted into the nuclear envelope (NE), preventing the cell from forming a bipolar mitotic spindle. We have previously shown that both MPS2 and NDC1 encode integral membrane proteins localized at the SPB. Here we show that CUE1, previously known to have a role in coupling ubiquitin conjugation to ER degradation, is an unusual dosage suppressor of mutations in MPS2 and NDC1. Cue1p has been shown to recruit the soluble ubiquitin-conjugating enzyme, Ubc7p, to the cytoplasmic face of the ER membrane where it can ubiquitinate its substrates and target them for degradation by the proteasome. Both mps2-1 and ndc1-1 are also suppressed by disruption of UBC7 or its partner, UBC6. The Mps2-1p mutant protein level is markedly reduced compared to wild-type Mps2p, and deletion of CUE1 restores the level of Mps2-1p to nearly wild-type levels. Our data indicate that Mps2p may be targeted for degradation by the ER quality control pathway.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder 80309-0347, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: McBratney
authors.forename: Mark
authors.initials: M
authors.lastname: Winey
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006358:Hot Temperature; D008025:Ligases / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000235:genetics* / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases
chemical_list: C109280:CUE1 protein, S cerevisiae; D002352:Carrier Proteins; C120755:MPS2 protein, S cerevisiae; D008565:Membrane Proteins; C082594:NDC1 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; C082461:UBC6 protein, S cerevisiae; C489967:UBE2J1 protein, human; C079437:UBE2L3 protein, human; D044763:Ubiquitin-Conjugating Enzymes; C104621:HRD1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D008025:Ligases