title: Mobilization of processed, membrane-tethered SPT23 transcription factor by CDC48(UFD1/NPL4), a ubiquitin-selective chaperone.
abstract: The OLE pathway of yeast regulates the level of the ER-bound enzyme Delta9-fatty acid desaturase OLE1, thereby controlling membrane fluidity. A central component of this regulon is the transcription factor SPT23, a homolog of mammalian NF-kappaB. SPT23 is synthesized as an inactive, ER membrane-anchored precursor that is activated by regulated ubiquitin/proteasome-dependent processing (RUP). We now show that SPT23 dimerizes prior to processing and that the processed molecule, p90, retains its ubiquitin modification and initially remains tethered to its unprocessed, membrane-bound SPT23 partner. Subsequently, p90 is liberated from its partner for nuclear targeting by the activity of the chaperone-like CDC48(UFD1/NPL4) complex. Remarkably, this enzyme binds preferentially ubiquitinated substrates, suggesting that CDC48(UFD1/NPL4) is qualified to selectively remove ubiquitin conjugates from protein complexes.
authors.affiliation: Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18a, 82152, Martinsried, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Rape
authors.forename: T
authors.initials: T
authors.lastname: Hoppe
authors.forename: I
authors.initials: I
authors.lastname: Gorr
authors.forename: M
authors.initials: M
authors.lastname: Kalocay
authors.forename: H
authors.initials: H
authors.lastname: Richly
authors.forename: S
authors.initials: S
authors.lastname: Jentsch
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000251:Adenosine Triphosphatases; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D019281:Dimerization; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D046911:Macromolecular Substances; D008565:Membrane Proteins; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins; D011485:Protein Binding; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D013230:Stearoyl-CoA Desaturase; D015534:Trans-Activators; D014157:Transcription Factors; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000378:metabolism*; D000074405:Valosin Containing Protein; D015003:Yeasts / Q000235:genetics / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D018832:Molecular Chaperones; C104361:NPL4 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D011498:Protein Precursors; D011506:Proteins; C087570:SPT23 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D025801:Ubiquitin; D044943:Fatty Acid Desaturases; D013230:Stearoyl-CoA Desaturase; C029627:delta-9 fatty acid desaturase; D000251:Adenosine Triphosphatases; C000614177:CDC48 protein, S cerevisiae; D000074405:Valosin Containing Protein