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PMID: 17289586 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

Molecular cell ·Vol. 25 ·No. 3 ·2007-02-09 ·Pages 385-97

Shcherbik N, Haines DS

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 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/metabolism,physiology Cell Cycle Proteins/metabolism,physiology Cell Membrane/enzymology Dimerization Endosomal Sorting Complexes Required for Transport Membrane Proteins Models, Biological Nuclear Pore Complex Proteins/metabolism,physiology Nucleocytoplasmic Transport Proteins Saccharomyces cerevisiae/enzymology Saccharomyces cerevisiae Proteins/chemistry,metabolism,physiology Trans-Activators/chemistry,metabolism Transcription Factors Ubiquitin/metabolism Ubiquitin-Protein Ligase Complexes/metabolism Valosin Containing Protein Vesicular Transport Proteins
Chemicals
Cell Cycle Proteins Endosomal Sorting Complexes Required for Transport Membrane Proteins NPL4 protein, S cerevisiae Nuclear Pore Complex Proteins Nucleocytoplasmic Transport Proteins SPT23 protein, S cerevisiae Saccharomyces cerevisiae Proteins Trans-Activators Transcription Factors UFD1 protein, S cerevisiae Ubiquitin Vesicular Transport Proteins Ubiquitin-Protein Ligase Complexes Adenosine Triphosphatases CDC48 protein, S cerevisiae Valosin Containing Protein RSP5 protein, S cerevisiae
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Shcherbik Natalia
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Haines Dale S
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-2765
DOI
10.1016/j.molcel.2007.01.024
Published
2007-02-09
Pages
385-97
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC1826656
Subset
IM
Grants
NIGMS NIH HHS · R01 GM070769 · United States
NIGMS NIH HHS · GM070769 · United States
External Links
PubMed source DOI: 10.1016/j.molcel.2007.01.024 PMC Full Text View journal details
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