Role of the ubiquitin-selective CDC48UFD1/NPL4 chaperone (segregase) in ERAD of OLE1 and other substrates

AUTOR(ES)

Braun, Sigurd

FONTE

Oxford University Press

RESUMO

The OLE pathway of yeast regulates the abundance of the ER-bound enzyme Δ-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 CDC48UFD1/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 CDC48UFD1/NPL4 plays a second role in the OLE pathway by mediating ERAD of OLE1. Intriguingly, other ERAD substrates also require CDC48UFD1/NPL4 for degradation, indicating that this enzyme is a novel, constitutive component of the ERAD machinery. We propose that CDC48UFD1/NPL4 functions as a segregase that liberates ubiquitylated proteins from non-modified partners.

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