Claims
- 1. A polypeptide, comprising:
an amino acid sequence at least 90% homologous to SEQ ID No 1.
- 2. A peptide, comprising:
an amino acid sequence for MTAF600 such that the amino acid sequence has at least 90% homology with amino acid sequence 3,910-4851 of SEQ ID No 1.
- 3. A peptide, comprising:
an amino acid sequence corresponding to aminoacid 4293-4534 of SEQ ID: No. 1.
- 4. A small molecule having a molecular weight of less than 1500D and capable of binding at least one of RB (379-928), P107, P130, E2F1-5 or microtubule.
- 5. A pharmaceutical composition, comprising an effective dose for treating a hyperproliferative condition of at least one of a polypeptide according to claim 1, a peptide according to claim 2 or 3, or a small molecule according to claim 4.
- 6. A method for treating a hyperproliferative disease, comprising:
administering an effective dose of a pharmaceutical composition according to claim 5.
- 7. A method according to claim 7, wherein the hyperproliferative condition is a cancer.
- 8. A method according to claim 7, wherein the cancer is retinoblastoma, osteosarcoma, lung cancer, breast cancer or bladder cancer.
- 9. A vector, comprising:
a nucleic acid sequence encoding SEQ ID No: 1 or a biologically active substituent thereof operably linked to a regulatory sequence for providing transcriptional activity in a host cell.
- 10. A vector according to claim 9, wherein the nucleic acid sequence comprises at least 50% of the nucleotides 11,728-14,553 of the gene sequence encoding MTAF600 corresponding to a peptide having amino acids 3,910-4851 or nucleotide 13,611-14,767 of the gene sequence encoding MTAF600 corresponding to a peptide having amino acids 4,293-4,534.
- 11. An in vitro cell culture, comprising a vector according to claim 9.
- 12. A method of diagnosing a susceptibility to cancer of a subject, comprising:
(a) obtaining a tissue sample from the subject and (b) screening the tissue sample for mutations in the chromosome 1 p36 relating to expression of MTAF600 protein.
- 13. A reagent for assaying for the presence of normal or mutated MTAF600, comprising at least one of a polyclonal antibody, a monoclonal antibodies or a Fab fragments having specificity for epitopes of intact MTAF600 or fragments thereof.
- 14. A reagent for assaying for the presence of normal or mutated MTAF600, comprising nucleic acid probes and primers for detecting DNA or mRNA encoding MTAF600 or fragments thereof.
- 15. A method of diagnosing a susceptibility to a cancer or a type of cancer in a subject, comprising, obtaining a cell sample from the subject, and subjecting the cell sample to an immunoassay according to claim 13 or to nucleic acid analysis according to claim 14.
- 16. An animal model, comprising:
a mouse having a deletion in its genome corresponding to the entire gene or a fragment of a gene at a locus selected from the RB gene and the MTAF600 gene.
- 17. A method of inhibiting E2F-mediated transcription in a cell, comprising:
administering to the cell, a polypeptide according to claim 1, a peptide according to claims 2 or 3 or a small molecule according to claim 4 that binds to retinoblastoma protein to inhibit the E2F-mediated transcription.
- 18. A method of treating a subject that has a heterozygous or homozygous mutation in the RB gene, comprising administering to the subject an effective amount of a polypeptide of claims 1, a peptide of claims 2 or 3 or a small molecule according to claim 4.
- 19. A method of treating a subject that has a heterozygous or homozygous mutation in the RB gene, comprising:
administering to the subject an effective amount of a peptide or small molecule that interacts with a polypeptide according to claim 1 or a peptide according to claims 2 or 3 to enhance tumor suppression.
- 20. A screening assay for identifying molecules with binding affinity to RB, comprising:
(a) selecting a protein having a large pocket corresponding to amino acids 379-928; (b) subjecting the protein to a library of small molecules so as to identify small molecules capable of binding the large pocket; and (c) testing the small molecule for competitive inhibition of binding of MTAF600 with RB.
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application gains priority from provisional application serial No. 60/278,245 and provisional application 60/278,244 both filed on Mar. 23, 2001 and incorporated herein by reference.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60278244 |
Mar 2001 |
US |
|
60278245 |
Mar 2001 |
US |