Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Patent
1995-11-13
1997-12-30
Guzo, David
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
435 71, 435 29, 4352542, 435325, C12Q 168, C12N 119
Patent
active
057029032
ABSTRACT:
A human gene has been discovered which is genetically altered in human tumor cells. The genetic alteration is gene amplification and leads to a corresponding increase in gene products. Detecting that the gene, designated hMDM2, has become amplified or detecting increased expression of gene products is diagnostic of tumorigenesis. Human MDM2 protein binds to human p53 and allows the cell to escape from p53-regulated growth. Methods of identifying compounds which interfere with the binding of human MDM2 protein to human p53 protein involved host cells which contain p-53-responsive reporter constructs and MDM2 polypeptides.
REFERENCES:
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Momand, et al., "The MDM2 Oncogene Product Forms a Complex with the p53 Protein and Inhibits p53-Mediated Transactivation," Cell:69:1237-1245 (1992).
Oliner, et al, "Amplification of a Gene Encoding a p53-Associated Protein in Human Sarcomas", Nature, 358:80-83 (1992).
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Leach, et al., "p53 Mutation and MDMS Amplification in Human Soft Tissue Sarcomas", Cancer Research 53:2231-2234 (1993).
Oliner, et al., "Oncoprotein MDM2 Conceals the Activation Domain of Tumour Suppressor p53", Nature, 362(6423):857-860 (1993).
Cahilly-Snyder, "Molecular Analysis and Chromosomal Mapping of Amplified Genes Isolated From a Transformed Mouse 3T3 Cell Line", Somatic Cell and Molecular Genetics, 13(3):235-244 (1987).
Kinzler Kenneth W.
Vogelstein Bert
Guzo David
The Johns Hopkins Unviersity
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