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.
Mesh Terms:
Adenosine Triphosphatases, Amino Acid Sequence, Cell Cycle Proteins, Molecular Sequence Data, Nuclear Pore Complex Proteins, Nuclear Proteins, Nucleocytoplasmic Transport Proteins, Saccharomyces cerevisiae Proteins, Sequence Homology, Amino Acid, Ubiquitin, Vesicular Transport Proteins
EMBO J.
Date: Feb. 15, 2002
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