title: Nucleocytoplasmic shuttling of valosin-containing protein (VCP/p97) regulated by its N domain and C-terminal region.
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.
authors.affiliation: Center for Inflammation, Translational and Clinical Lung Research, School of Medicine, Temple University, Philadelphia, PA 19140, USA. Electronic address: songc@temple.edu.
authors.forename: Changcheng
authors.initials: C
authors.lastname: Song
authors.affiliation: Graduate Center for Toxicology, University of Kentucky, Lexington, KY, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Erythrocrine Project of Translational Medicine, Shandong Academy of Medical Sciences, Jinan 250062, China.
authors.forename: Changzheng
authors.initials: C
authors.lastname: Song
authors.affiliation: Optical Microscopy and Analysis Laboratory, Advanced Technology Program, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lockett
authors.affiliation: Laboratory of Cancer Prevention, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
authors.forename: Nancy H
authors.initials: NH
authors.lastname: Colburn
authors.affiliation: 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.
authors.forename: Chou-Chi H
authors.initials: CC
authors.lastname: Li
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
authors.forename: Ji Ming
authors.initials: JM
authors.lastname: Wang
authors.affiliation: Center for Inflammation, Translational and Clinical Lung Research, School of Medicine, Temple University, Philadelphia, PA 19140, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Rogers
mesh_terms: D021581:Active Transport, Cell Nucleus; D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D057180:Frontotemporal Dementia / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics; D018979:Myositis, Inclusion Body / Q000235:genetics; D010001:Osteitis Deformans / Q000235:genetics; D017434:Protein Structure, Tertiary; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein
keywords: Inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD); Nuclear export signal; Nucleocytoplasmic shuttling; Valosin containing protein