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Biochim Biophys Acta. 2015 Jan;1853(1):222-32. doi: 10.1016/j.bbamcr.2014.10.019. Epub 2014 Oct 30.

Nucleocytoplasmic shuttling of valosin-containing protein (VCP/p97) regulated by its N domain and C-terminal region.

Author information

1
Center for Inflammation, Translational and Clinical Lung Research, School of Medicine, Temple University, Philadelphia, PA 19140, USA. Electronic address: songc@temple.edu.
2
Graduate Center for Toxicology, University of Kentucky, Lexington, KY, USA.
3
Erythrocrine Project of Translational Medicine, Shandong Academy of Medical Sciences, Jinan 250062, China.
4
Optical Microscopy and Analysis Laboratory, Advanced Technology Program, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
5
Laboratory of Cancer Prevention, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
6
Laboratory of Cancer Prevention, National Cancer Institute at Frederick, Frederick, MD 21702, USA; Basic Research Program, SAIC-Frederick Inc., National Cancer Institute at Frederick, Frederick, MD 21702, USA.
7
Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
8
Center for Inflammation, Translational and Clinical Lung Research, School of Medicine, Temple University, Philadelphia, PA 19140, USA.

Abstract

Valosin-containing protein (VCP or p97), a member of the AAA family (ATPases associated with diverse cellular activities), plays a key role in many important cellular activities. A genetic deficiency of VCP can cause inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD). Previous studies showed that the VCP N domain is essential for the regulation of nuclear entry of VCP. Here we report that IBMPFD mutations, which are mainly located in the N domain, suppress the nuclear entry of VCP. Moreover, the peptide sequence G780AGPSQ in the C-terminal region regulates the retention of VCP in the nucleus. A mutant lacking this sequence can increase the nuclear distribution of IBMPFD VCP, suggesting that this sequence is a potential molecular target for correcting the deficient nucleocytoplasmic shuttling of IBMPFD VCP proteins.

KEYWORDS:

Inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD); Nuclear export signal; Nucleocytoplasmic shuttling; Valosin containing protein

PMID:
25447673
PMCID:
PMC4254625
DOI:
10.1016/j.bbamcr.2014.10.019
[Indexed for MEDLINE]
Free PMC Article

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