Claims
- 1. A substantially pure polypeptide comprising SEQ ID NO:1, wherein said polypeptide inhibits degradation of endogenous p53 in a mammalian cell.
- 2. The polypeptide of claim 1, wherein said polypeptide comprises residues 1-113 of p53.
- 3. The polypeptide of claim 1, wherein the polypeptide comprises the proline-rich domain (PRD) of p53.
- 4. The polypeptide of claim 1, wherein the polypeptide does not comprise the N-terminal acidic transactivation domain (TAD) of p53.
- 5. The polypeptide of claim 1, wherein the polypeptide does not comprise a DNA binding domain (DBD) of p53.
- 6. The polypeptide of claim 1, wherein the polypeptide does not comprise the oligomerization domain (OD) of p53.
- 7. The polypeptide of claim 1, wherein the polypeptide does not comprise residues 1-42 of p53.
- 8. The polypeptide of claim 1, wherein said polypeptide is at least 20 residues in length and less than 393 amino acids in length.
- 9. A peptide mimetic comprising the amino acid sequence of SEQ ID NO:1.
- 10. A substantially pure polypeptide comprising SEQ ID NO:2, wherein said polypeptide inhibits degradation of endogenous p53 in a mammalian cell.
- 11. A peptide mimetic comprising the amino acid sequence of SEQ ID NO:2.
- 12. A method of inhibiting p53 degradation in a cell comprising contacting said cell with a synthetic polypeptide comprising SEQ ID NO:1.
- 13. The method of claim 12, wherein the polypeptide comprises residues 1-112 of human p53.
- 14. The method of claim 12, wherein the polypeptide comprises the proline-rich domain of human p53.
- 15. The method of claim 12, wherein said polypeptide is at least 20 residues in length and less than 393 amino acids in length.
- 16. The method of claim 12, wherein said dell is a cervical cancer cell.
- 17. The method of claim 12, wherein said cell comprises a Mdm2 amplification.
- 18. The method of claim 12, wherein said cell overexpresses Mdm2.
- 19. The method of claim 12, wherein said cell is tumor cell selected from the group consisting of a sarcoma and a carcinoma.
- 20. The method of claim 12, wherein said cell is a tumor cell selected from the group consisting of a squamous cell carcinoma, ovarian cancer, lung cancer, pancreatic cancer, leukemia, lymphoma, glioma, and neuroblastoma.
- 21. The method of claim 12, wherein said cell is a tumor cell selected from the group consisting of an osteosarcoma, colon carcinoma, melanoma, choriocarcinoma, breast carcinoma, glioblastoma, neuroblastoma, and rhadomyosarcoma.
- 22. An isolated DNA encoding the polypeptide of claim 1.
- 23. A degradation-resistant p53 polypeptide.
- 24. The polypeptide of claim 23, wherein said polypeptide does not comprise SEQ ID NO: (AA 92-112).
- 24. The polypeptide of claim 23, wherein said polypeptide retains at least 50% of the tumor suppressive activity of a naturally-occurring p53 protein.
- 25. The polypeptide of claim 23, wherein said polypeptide is transcriptionally active.
- 26. The polypeptide of claim 23, wherein said polypeptide induces apoptosis.
- 27. An isolated DNA encoding the polypeptide of claim 23.
- 28. A method of inhibiting tumor growth, comprising contacting a tumor cell with the polypeptide of claim 23.
- 29. The method of claim 28, wherein said tumor is a cervical cancer.
- 30. The method of claim 28, wherein said tumor comprises a p53 mutation.
RELATED APPLICATION
[0001] This application claims the benefit from provisional application Serial No. 60/169,816, which was filed on Dec. 8, 1999.
STATEMENT AS TO FEDERALLY SPONSORED RESEARCH
[0002] This invention was funded in part by the U.S. Government under Grant Number R29CA76275 awarded by the National Institutes of Health. The Government has certain rights in the invention.
Provisional Applications (1)
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Number |
Date |
Country |
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60169816 |
Dec 1999 |
US |