Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
2000-01-10
2001-07-03
Carlson, Karen Cochrane (Department: 1653)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S024310, C435S069100, C435S252300, C435S254100, C435S320100, C435S325000, C530S350000
Reexamination Certificate
active
06255472
ABSTRACT:
TECHNICAL FIELD
The present invention relates to genes which are useful for prevention of human diseases and for establishing guidelines for diagnosis and therapeutic treatment, and more particularly, to human genes which are transcriptionally regulated specifically by a tumor suppressor gene p53, as well as to genes which can feasibly be used for gene diagnosis and development of new therapeutic methods.
BACKGROUND ART
Among genetic alterations found in human cancer, mutations of a tumor suppressor gene p53 are most prevalently seen, and thus the p53 gene is believed to be one of the most important genes relevant to tumorigenicity in the human body (Hollstein M. et al., Science (Washington DC), 253: 49-53, 1991). The p53 gene functions as a transcription factor (Vogelstein B., et al., Cell, 70: 523-526, 1992), and it has been confirmed that, upon its binding to a specific DNA sequence, p53 can activate various genes, including p21/WAF1, MDM2, GADD45, BAX, cyclin G, IGF-BP3, PCNA, and GML (EI-Deiry, W. S., et al., Cell, 75: 817-825, 1993; Wu X., et al., Genes Dev., 7: 1126-1132, 1993; Kastan M. B., et al., Cell, 71: 587-597, 1992; Miyashita T., et al., Cell, 80: 293-299, 1995; Okamoto K., et al., EMBO. J., 13: 4816-4822, 1994; Buckbinder L., et al., Nature, 377: 646-649, 1995; Morris G. E., et al., Proc. Natl. Acad. Sci. USA, 93: 885-899, 1996; and Furuhata T., et. al., Oncogene, 13: 1965-1970, 1996). Among these genes, p21/WAF1, BAX, and GML are thought to be major factors involving cell cycle arrest and apoptosis mediated through p53, whereas GADD45 plays an important role in DNA repair.
Thus, identification of genes regulated by p53 is vital for understanding biological and physiological functions of p53. Furthermore, identification of p53-target genes and elucidation of their functions are eagerly awaited not only by cancer researchers but also by researchers who hope to develop new methods of diagnosis and treatment of cancer through use of such target genes.
It should be noted that the present inventors have already designed and established a method of finding candidates for p53-target genes in the vicinity of functional p53-binding sites (p53-tagged sites) in the human genome. Using the method, the present inventors have successfully demonstrated isolation of the GML gene, whose expression is believed to be positively correlated with sensitivity to anticancer drugs (Furuhata T., et al., Oncogene, 13: 1965-1970, 1996).
An object of the present invention is to provide the demanded information which is vitally important to the above fields; that is, to provide information which can enable finding and identification of target genes for the tumor suppressor gene p53 (p53-target genes) or p53-inducible genes, i.e. novel human genes whose expressions fall under specific transcriptional regulation by p53.
DISCLOSURE OF THE INVENTION
Upon cloning functional p53-tagged sites from the human genome, the present inventors have isolated a novel human gene which can be induced by wild-type p53, and have further demonstrated that the isolated novel gene satisfies the above object, thus successfully completing the invention.
Accordingly, the present invention provides a human gene comprising a nucleotide sequence encoding the entirety of or a portion of the amino acid sequence shown in SEQ ID NO:3, and, in particular, a gene which comprises the entirety of or a portion of the nucleotide sequence shown in SEQ ID NO:1.
REFERENCES:
Collo et al,J. of Neuroscience,16(8):2495-2507 (1996).
Soto et al,Biochem. and Biophys. Res. Comm.,223 (2):456-460 (1996).
Valera et al,Receptors and Channels, Ch, Harwood Academic Publishers,3(4):283-289 (1995).
Seguela et al,J. of Neuroscience,US, New York, NY, 16(2):448-455 (1996).
Nakamura Yusuke
Tokino Takashi
Carlson Karen Cochrane
Otsuka Pharmaceutical Co. Ltd.
Sughrue Mion Zinn Macpeak & Seas, PLLC
Tu Stephen
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