Role of the ubiquitin-selective CDC48(UFD1/NPL4 )chaperone (segregase) in ERAD of OLE1 and other substrates.
The OLE pathway of yeast regulates the abundance of the ER-bound enzyme Delta-9 fatty acid desaturase OLE1, thereby controlling unsaturated fatty acid pools and membrane fluidity. Previously, we showed that this pathway is exquisitely regulated by the ubiquitin/proteasome system. Activation of the pathway involves proteasomal processing of a membrane-bound transcription factor and the subsequent mobilization of the cleaved, ubiquitylated transcription factor from its partner molecule by CDC48(UFD1/NPL4), a ubiquitin-selective chaperone-like enzyme. Here we report that the OLE1 protein itself is naturally short-lived and is degraded by ubiquitin/proteasome-dependent ER-associated degradation (ERAD). We found that CDC48(UFD1/NPL4) plays a second role in the OLE pathway by mediating ERAD of OLE1. Intriguingly, other ERAD substrates also require CDC48(UFD1/NPL4) for degradation, indicating that this enzyme is a novel, constitutive component of the ERAD machinery. We propose that CDC48(UFD1/NPL4) functions as a segregase that liberates ubiquitylated proteins from non-modified partners.
Braun
Sigurd
S
Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18a, D-82152 Martinsried, Germany.
Matuschewski
Kai
K
Rape
Michael
M
Thoms
Sven
S
Jentsch
Stefan
S
D000251:Adenosine Triphosphatases; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D029543:Nucleocytoplasmic Transport Proteins; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D025801:Ubiquitin / Q000378:metabolism*; D000074405:Valosin Containing Protein; D033921:Vesicular Transport Proteins
D018797:Cell Cycle Proteins; C104361:NPL4 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; C444652:UFD1 protein, S cerevisiae; D025801:Ubiquitin; D033921:Vesicular Transport Proteins; D000251:Adenosine Triphosphatases; C000614177:CDC48 protein, S cerevisiae; D000074405:Valosin Containing Protein