Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1950536 | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | 2015 | 11 Pages |
•IBMPFD mutations decrease the nuclear distribution of VCP.•The peptide G780AGPSQ of VCP regulates its retention in the nucleus and nucleoli.•C-terminal region deletion elevates the nuclear retention of VCP IBMPFD mutants.
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.