Werner syndrome protein directly binds to the AAA ATPase p97/VCP in an ATP-dependent fashion.

Abstract	We have previously shown that the Werner syndrome helicase, WRNp, a member of the RecQ helicase family, forms a tight molecular complex with the p97/Valosin containing protein (VCP), a member of the AAA (ATPases associated with diverse cellular activities) family of proteins. This interaction is disrupted by chemical agents that confer DNA damage, suggesting that VCP plays an important role in the signal-dependent release of WRNp from its nucleolar sequestration site. Here, we characterized the structural requirements for interactions between WRNp and VCP and for the nuclear localization of VCP. We discovered that VCP directly binds to the RQC (RecQ conserved) domain of WRNp, which is a highly conserved motif common to the RecQ helicase family. This interaction is ATP-dependent, suggesting that VCP plays a mechanistic role in releasing WRNp from the nucleolus. Immunohistochemical analysis of various VCP domains and mutated proteins expressed in vitro demonstrated that VCP may contain several hierarchical cellular localization motifs within its domain structure.
Authors	Fred Eliezer Indig, Juneth Joaquin Partridge, Cayetano von Kobbe, Mirit I Aladjem, Martin Latterich, Vilhelm A Bohr
Journal	Journal of structural biology (J Struct Biol) 2004 Apr-May Vol. 146 Issue 1-2 Pg. 251-9 ISSN: 1047-8477 [Print] United States
PMID	15037256 (Publication Type: Journal Article)
Chemical References	Cell Cycle Proteins Macromolecular Substances Peptide Fragments Adenosine Triphosphate Exodeoxyribonucleases Adenosine Triphosphatases DNA Helicases RecQ Helicases WRN protein, human Werner Syndrome Helicase VCP protein, human Valosin Containing Protein
Topics	Active Transport, Cell Nucleus Adenosine Triphosphatases (metabolism) Adenosine Triphosphate (pharmacology) Animals Binding Sites Cattle Cell Cycle Proteins (metabolism) Conserved Sequence DNA Helicases (metabolism) Exodeoxyribonucleases HeLa Cells Humans Immunohistochemistry Macromolecular Substances Mutation Peptide Fragments (metabolism) Protein Binding RecQ Helicases Valosin Containing Protein Werner Syndrome Helicase

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