VCP, a weak ATPase involved in multiple cellular events, interacts physically with BRCA1 in the nucleus of living cells.
BRCA1, a breast/ovarian cancer susceptibility gene, undergoes mutations in as many as 50% of familial breast tumors. Recent studies indicate that BRCA1 may be involved in DNA damage repair. Here, we demonstrate that the BRCA1 protein physically associates with valosin-containing protein (VCP), a member of the ATPases associated with a variety of cellular activities (AAA) superfamily. In vitro studies revealed that VCP, via its N- terminal region, binds to amino acid residues 303-625 in the BRCA1 protein. Although found predominantly in the cytoplasm and, less abundantly, in the nucleus, VCP can be translocated from the nucleus after stimulation with epidermal growth factor. Collectively, our results suggest that VCP, by binding to BRCA1, participates in the DNA damage-repair function as an ATP transporter, possibly facilitating the transcription-coupled repair.
Zhang
H
H
Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia 19104-6082, USA.
Wang
Q
Q
Kajino
K
K
Greene
M I
MI
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D019313:BRCA1 Protein / Q000276:immunology / Q000378:metabolism*; D001665:Binding Sites; D001692:Biological Transport; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D006801:Humans; D008970:Molecular Weight; D010766:Phosphorylation; D011233:Precipitin Tests; D017421:Sequence Analysis; D014407:Tumor Cells, Cultured; D000074405:Valosin Containing Protein
D000911:Antibodies, Monoclonal; D019313:BRCA1 Protein; D018797:Cell Cycle Proteins; D004815:Epidermal Growth Factor; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein