Isolated BRCA1 peptides and method of use
View Patent ↗The invention provides isolated peptides of a BRCA1 domain, which bind to p53 cognate DNA and stimulate transcription activities and cancer cell apoptosis. Nucleic acids encoding the peptides, and methods of expression thereof, are also provided. The invention provides pharmaceutical compositions, and methods of use thereof, for treating breast and ovarian cancer using the peptides.
1. A composition comprising an isolated peptide domain of a wild-type BRCA1 protein, said peptide domain consists of the BRCA1 amino acids 772-1292 (SEQ ID NO:1), amino acids 1036-1292 (SEQ ID NO:10), or amino acids 904-1292 (SEQ ID NO:11), wherein said peptide domain stimulates p53 cognate DNA binding and transcription activities, resulting in cell apoptosis in a cancer cell in the presence of p53.
2. The composition of claim 1 , wherein said peptide domain consists of the amino acid sequence of SEQ ID NO:1.
3. The composition of claim 1 , wherein said peptide domain consists of the amino acid sequence of SEQ ID NO:11.
4. The composition of claim 1 , further comprising a pharmaceutically acceptable carrier.
5. A method of stimulating transcription activities resulting in cancer cell apoptosis comprising binding said peptide domain of claim 1 to p53 cognate DNA in a cancer cell in the presence of p53.
6. The method of claim 5 , wherein said cancer cell is breast cancer cell.
7. The method of claim 5 , wherein said cancer cell is ovarian cancer cell.
8. A method of making the peptide domain of claim 1 comprising recombinantly expressing a nucleic acid encoding said peptide domain.
9. The method of claim 8 , wherein said nucleic acid encodes the peptide domain consisting of the amino acid sequence of SEQ ID NO:1.
10. The method of claim 8 , wherein said nucleic acid encodes the peptide domain consisting of the amino acid sequence of SEQ ID NO:11.
11. The composition of claim 1 , wherein said peptide domain consists of the amino acid sequence of SEQ ID NO:10.
12. The method of claim 5 , wherein said peptide domain consists of the amino acid sequence of SEQ ID NO:1.
13. The method of claim 5 , wherein said peptide domain consists of the amino acid sequence of SEQ ID NO:10.
14. The method of claim 5 , wherein said peptide domain consists of the amino acid sequence of SEQ ID NO:11.
15. The method of claim 8 , wherein said nucleic acid encodes the peptide domain consisting of the amino acid sequence of SEQ ID NO:10.