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

被引：38
作者：
Indig, FE [1 ]
Partridge, JJ
von Kobbe, C
Aladjem, MI
Latterich, M
Bohr, VA
机构：
[1] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA
[2] NCI, Cell Biol Lab, CCR, NIH, Bethesda, MD 20892 USA
[3] NCI, Mol Pharmacol Lab, CCR, NIH, Bethesda, MD 20892 USA
[4] McGill Univ, Dept Anat & Cell Biol, Montreal, PQ H3A 2B2, Canada
来源：
JOURNAL OF STRUCTURAL BIOLOGY | 2004年 / 146卷 / 1-2期
关键词：
cdc48p; p97; VCP; Werner syndrome; AAA domain; GFP;
D O I：
10.1016/j.jsb.2003.11.009
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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. Published by Elsevier Inc.
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页码：251 / 259
页数：9
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