Cdc48pNpl4p/Ufd1p Binds and Segregates Membrane-Anchored/Tethered Complexes via a Polyubiquitin Signal Present on the Anchors

Natalia Shcherbik, Dale S. Haines

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

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 Cdc48pNpl4p/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 Cdc48pNpl4p/Ufd1p functions as a polyubiquitin-selective segregase and that a polyubiquitin-Cdc48p pathway modulates protein interactions at cell membranes.

Original languageEnglish (US)
Pages (from-to)385-397
Number of pages13
JournalMolecular Cell
Volume25
Issue number3
DOIs
StatePublished - Feb 9 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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