title: Cdc48 and Ubx1 participate in a pathway associated with the inner nuclear membrane that governs Asi1 degradation.
abstract: The nuclear envelope is a barrier comprising outer and inner membranes that separate the cytoplasm from the nucleoplasm. The two membranes have different physical characteristics and protein compositions. The processes governing the stability of inner nuclear membrane (INM) proteins are not well characterized. In Saccharomyces cerevisiae, the INM Asi1-Asi3 complex, principally composed of integral membrane proteins Asi1 and Asi3, is an E3 ubiquitin ligase. In addition to its well-documented function in endoplasmic reticulum (ER)-associated degradation, the Doa10 E3 ubiquitin ligase complex partially localizes to the INM. The Asi1-Asi3 and Doa10 complexes define independent INM-associated degradation (INMAD) pathways that target discrete sets of nuclear substrates for proteasomal degradation. Here, we report that Asi1 is rapidly turned over (t1/2≤30 min). Its turnover depends on ubiquitin-mediated degradation by nucleus-localized proteasomes, exhibiting a clear requirement for the E2 ubiquitin-conjugating enzyme Ubc7, Cue1 and the AAA ATPase Cdc48 and co-factor Ubx1. Asi1 turnover occurs largely independently of the Asi1-Asi3 or Doa10 complexes, indicating that it is subject to quality control at the INM in a manner distinct from that of the characterized INMAD pathways.
authors: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm SE-106 91, Sweden.
authors: Marina
authors: M
authors: Pantazopoulou
authors: University of Zagreb, School of Medicine, Croatian Institute for Brain Research, Šalata 12, Zagreb 10000, Croatia.
authors: Mirta
authors: M
authors: Boban
authors: Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University of Vienna, Dr. Bohr-Gasse 9, Vienna A-1030, Austria.
authors: Roland
authors: R
authors: Foisner
authors: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm SE-106 91, Sweden per.ljungdahl@su.se.
authors: Per O
authors: 0000-0002-6625-3540
authors: PO
authors: Ljungdahl
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D060746:Endoplasmic Reticulum-Associated Degradation; D005820:Genetic Testing; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D009685:Nuclear Envelope / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D000074405:Valosin Containing Protein
chemical_list: C438144:ASI1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C106691:SHP1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; C000614177:CDC48 protein, S cerevisiae; D000074405:Valosin Containing Protein
keywords: INMAD; Inner-nuclear-membrane-associated degradation; Membrane dislocation; Nuclear envelope; Proteasome; Saccharomyces cerevisiae; Ubiquitin