Werner syndrome protein directly binds to the AAA ATPase p97/VCP in an ATP-dependent fashion.
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.
Indig
Fred Eliezer
FE
Laboratory of Molecular Gerontology, NIA, NIH, Baltimore MD 21224, USA. indigfr@grc.nia.nih.gov
Partridge
Juneth Joaquin
JJ
von Kobbe
Cayetano
C
Aladjem
Mirit I
MI
Latterich
Martin
M
Bohr
Vilhelm A
VA
D021581:Active Transport, Cell Nucleus; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D017124:Conserved Sequence; D004265:DNA Helicases / Q000378:metabolism*; D005090:Exodeoxyribonucleases; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D046911:Macromolecular Substances; D009154:Mutation; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D053484:RecQ Helicases; D000074405:Valosin Containing Protein; D000071657:Werner Syndrome Helicase
D018797:Cell Cycle Proteins; D046911:Macromolecular Substances; D010446:Peptide Fragments; D000255:Adenosine Triphosphate; D005090:Exodeoxyribonucleases; D000251:Adenosine Triphosphatases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase; C000614178:VCP protein, human; D000074405:Valosin Containing Protein