Cdc48p(Npl4p/Ufd1p) binds and segregates membrane-anchored/tethered complexes via a polyubiquitin signal present on the anchors.

Cdc48p is an abundant and conserved member of the AAA ATPase family of molecular chaperones. Cdc48p performs ubiquitin-selective functions, which are mediated by numerous ubiquitin binding adaptors, including the Npl4p-Ufd1p complex. Previous studies suggest that Cdc48p-containing complexes carry out many biochemical activities, including ubiquitination, deubiquitination, protein complex segregation, and targeting ...
of ubiquitinated substrates to the proteasome. The molecular mechanisms by which Cdc48p-containing complexes participate in these processes remain poorly defined. We show here by using physiologically relevant Cdc48p substrates (i.e., endoplasmic membrane-associated/tethered dimers of Mga2p and Spt23p) and in vitro systems with purified proteins that Cdc48p(Npl4p/Ufd1p) binds to and promotes segregation of the tethered proteins via a polyubiquitin signal present on the membrane-bound proteins. Mobilization does not involve retrotranslocation of the associated anchors. These results provide biochemical evidence that Cdc48p(Npl4p/Ufd1p) functions as a polyubiquitin-selective segregase and that a polyubiquitin-Cdc48p pathway modulates protein interactions at cell membranes.
Mesh Terms:
Adenosine Triphosphatases, Cell Cycle Proteins, Cell Membrane, Dimerization, Endosomal Sorting Complexes Required for Transport, Membrane Proteins, Models, Biological, Nuclear Pore Complex Proteins, Nucleocytoplasmic Transport Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Trans-Activators, Transcription Factors, Ubiquitin, Ubiquitin-Protein Ligase Complexes, Vesicular Transport Proteins
Mol. Cell
Date: Feb. 09, 2007
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