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

• Published in: Molecular cell Vol. 25; no. 3; pp. 385 - 397
• Main Authors: Shcherbik, Natalia, Haines, Dale S
• Format: Journal Article
• Language: English
• Published: United States 09.02.2007
• Subjects: Adenosine Triphosphatases - metabolism; Adenosine Triphosphatases - physiology; Cell Cycle Proteins - metabolism; Cell Cycle Proteins - physiology; Cell Membrane - enzymology; Dimerization; Endosomal Sorting Complexes Required for Transport; Membrane Proteins; Models, Biological; Nuclear Pore Complex Proteins - metabolism; Nuclear Pore Complex Proteins - physiology; Nucleocytoplasmic Transport Proteins; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - metabolism; Saccharomyces cerevisiae Proteins - physiology; Trans-Activators - chemistry; Trans-Activators - metabolism; Transcription Factors; Ubiquitin - metabolism; Ubiquitin-Protein Ligase Complexes - metabolism; Valosin Containing Protein; Vesicular Transport Proteins
• ISSN: 1097-2765
• DOI: 10.1016/j.molcel.2007.01.024

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.