Methods for determining the presence of functional p53 in mammal

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid

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536 235, C12Q 168, C07H 2102

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056164637

ABSTRACT:
The dependence of ionizing radiation-induced GADD45 mRNA expression on the presence of functional p53 in mammalian cells is disclosed. First and second oligonucleotide sequences are provided which can form a double-stranded oligomer capable of binding to functional p53 protein. The present invention demonstrates that the dependence of ionizing radiation-induced GADD45 mRNA expression on the presence of functional p53 and the binding of functional p53 to a double-stranded oligomer binding sequence can serve as the basis for methods for determining the presence of functional p53 in mammalian cell lines and tumors.

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Chemical Abstracts, vol. 117, No. 7, issued 17 Aug. 1992 (Columbus, Ohio USA) B.D. Price et al. "Gadd45 and Gadd153 messenger RNA levels are increased during hypoxia and after exposure of cells to agents which elevate the levels of the glucose-hypoxia and after exposure of cells to agents which elevate the levels of the glucose-regulated proteins." p. 561, abstract No. 67442y and Cancer Res. (1992) 52:3814-3817.
Chemical Abstracts, vol. 115, No. 11, issued 16 Sep. 1991 (Columbus, Ohio USA) M.A. Papathanasiou et al. "Induction by ionizing radaition of the gadd45 gene in cultured human cells: lack of mediation by protein kinase C." p. 419, abstract No. 109459a and Mol. Cell. Biol. (1991) 11:1009-1016.
Chemical Abstracts, vol. 101, No. 19, issued 05 Nov. 1984 (Columbus, Ohio USA), D. Wolf et al. "Reconstitution of p53 expression in a nonproducer Ab-MuLV-transformed cell line by transfection of a functional p53 gene." p. 153, abstract No. 164671z and Cell (1984) 38:199-226.
Kern, et al., "Identification of p53 as a Sequence-Specific DNA-Binding Protein." Science, 252: 1708-1711 (1991).
Kern et al., "Oncogenic Forms of p53 Inhibit p53-Regulated Gene Expression." Science, 256: 827-830 (1992).
Funk et al., "A Transcriptionally Active DNA-Binding Site For Human p53 Protein Complexes." Mol. Cell. Biol., 12: 2866-2870 (1992).
El-Deiry et al., "Definition of a Consensus Binding Site for p53."
Kastan et al., "Participation of p53 Protein in the Cellular Response to DNA Damage." Cancer Res. 51:6304-6311 (1991).
Kuerbitz et al., "Wild-Type p53 Is A Cell Cycle Checkpoint Determinant Following Irradiation." Proc. Natl. Acad. Sci. U.S.A., 89:7491-7495 (1992).
Fornace et al., "DNA Damage-Inducible Transcripts In Mammalian Cells." Proc. Natl. Acad. Sci. U.S.A., 85:8800-8804 (1988).
Fornace et al.,"Mammalian Genes Coordinately Regulated by Growth Arrest Signals and DNA-Damaging Agents." Mol. Cell Biol., 9:4196-4203 (1989).
Papathanasiou et al., "Induction by Ionizing Radiation of the gadd45 Gene in Cultured Human Cells: Lack of Mediation by Protein Kinase C." Mol. Cell Biol. 11: 1009-1016(1992).
Bargonetti et al., "Wild-Type but Not Mutant p53 Immunopurified Proteins Bind to Sequences Adjacent to the SV40 Origin of Replication." Cell, 65:1083-1091. (1991)

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