Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues
Patent
1997-11-13
1999-11-16
Degen, Nancy
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
530300, C07K 1447
Patent
active
059860553
ABSTRACT:
The present invention relates to complexes of the CDK2 protein with proteins identified as interacting with CDK2 by a modified yeast two hybrid assay system. The proteins identified to interact with CDK2 are cyclin H, cyclin I, ERH, and two gene products, hsReq*-1 and hsReq*-2, which are splice variants of the gene hsReq. Thus, the invention provides complexes of CDK2 and cyclin H, cyclin I, ERH, hsReq*-1, and hsReq*-2, and derivatives, fragments and analogs thereof. The invention also provides nucleic acids encoding the hsReq*-1 and hsReq*-2, and proteins and derivatives, fragments and analogs thereof. Methods of screening the complexes for efficacy in treating and/or preventing certain diseases and disorders, particularly cancer, atherosclerosis and neurodegenerative disease are also provided.
REFERENCES:
Harper, et al., "The p21 Cdk-Interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases" Cell 75:805-816 (1993).
Elledge and Spottswood, (1992) "A new human p34 protein kinase, CDK2, identified by complementation of cdc28 mutation in Saccharomyces cerevisiae, is a homolog of Xenopus Eg1." EMBO J. 10(9):2653-2659, Accession No. X61622, Jan. 15, 1992.
Ohnishi, (1996) "Direct Submission." GenBank, Accession No. D85785, Feb. 6, 1999.
Nakamura, (1995) "Direct Submission." GenBank, Accession No. D50310, Feb. 10, 1999.
Gabig, et al., (1994) "Requlem: a novel zinc finger gene essential for apoptosis in myeloid cells." J. Biol. Chem. 269(47):29515-29519, Accession No. U94585, May 27, 1997.
Makela, et al., (1994) "A cyclin associated with the CDK-activating kinase MO15." Nature 371:254-257, Accession No. U11791, Sep. 8, 1994.
Adams et al., 1996, "Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors", Mol. Cell. Biol. 16:6623-6633.
Amundadittir et al., 1996, "Transgenic mouse models of breast cancer", Breast Cancer Res. Treat. 39:119-135.
Applebaum, 1997, "Graft versus leukemia (GVL) in the therapy of acute lymphoblastic leukemia (ALL)", Leukemia 11 (Supp4):S15-S17.
Callow, 1995, "Molecular biology of graft occlusion", Curr. Opin. Cardiol. 10:569-576.
Carlson et al., 1996, "Flavopiridol induces G.sub.1 arrest with inhibition of cyclin-dependent kinase (CDK) 2 and CDK4 in human breast carcinoma cells", Cancer Res. 56:2973-2978.
Chen et al., 1997, "Downregulation of cyclin-dependent kinase 2 activity and cyclin A promoter activity in vascular smooth muscle cells by p27.sup.KIP1, an inhibitor of neointima formation in the rat carotid artery", J. Clin. Invest. 99:2334-2341.
Dankort and Muller, 1996, "Transgenic models of breast cancer metastasis", Cancer Treat. Res. 83:71-88.
Donehower, 1996, "The p53-deficient mouse: a model for basic and applied cancer studies", Semin. Cancer. Biol. 7:269-278.
Drapkin et al., 1996, "Human cyclin-dependent kinase-activating kinase exists in three distinct complexes", Proc. Natl. Acad. Sci. USA 93:6488-6493.
Ellege and Spottswood, 1991, "A new human p34 protein kinase, CDK2, identified by complementation of a cdc28 mutation in Saccharomyces cerevisiae, is a homolog of Xenopus Eg1", EMBO J. 10:2653-2659.
Farber et al., 1992, "Cytokine secretion by human aortic endothelial cells is related to degree of atherosclerosis", Am. J. Physiol. 262:H1088-1085.
Farine, 1997, "Animal models in autoimmune disease in immunotoxicity assessment", Toxicol. 119:29-35.
Fisher and Morgan, 1994, "A novel cyclin associates with MO15/CDK7 to form the CDK-activating kinase", Cell 78:713-724.
Frey, 1997, "Study of immune response to tumors in the rat", Methods 12:173-188.
Frostegard et al., 1996, "Induction of heat shock protein in monocyte cells by oxidized low density lipoprotein", Atherosclerosis 121:93-103.
Gabig et al., 1994, "Requiem: a novel zinc finger gene essential for apoptosis in myeloid cells", J. Biol. Chem. 269:29515-29519.
Gibson et al., 1994, "Evidence for a protein domain superfamily shared by the cyclins, TFIIB and RB/p107", Nucl. Acids Res. 22:946-952.
Gutman and Fidler, 1995, "Biology of human colon cancer metastasis", World J. Surg. 19:226-234.
Higashi et al., 1996, "Cyclin-dependent kinase-2 (Cdk2) forms an active complex with cyclin D1 since Cdk2 associated with cyclin D1 is not phosphorylated by Cdk7-cyclin-H", Eur. J. Biochem. 237:460-467.
Holtzman et al., 1996, "Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome", Proc. Natl. Acad. Sci. USA 93:13333-13338.
Hung et al., 1992, "Increased expression of beta-amyloid precursor protein during neuronal differentiation is not accompanied by a secretory cleavage", Proc. Natl. Acad. Sci. USA 89:9439-9443.
Isselbacher et al., "Principals of Neoplasia" Harrison's Principals of Internal Medicine, 13th Edition (McGraw Hill, New York) p. 1814.
Jarrett et al., 1995, "Model of human transitional cell carcinoma: tumor xenografts in upper urinary tract of nude rat", J. Endurol. 9:1-7.
Johnson-Wood et al., 1997, "Amyloid precursor protein processing and A beta42 deposition in a transgenic mouse model of Alzheimer disease", Proc. Natl. Acad. Sci. USA 94:1550-1555.
Kappel et al., 1994, "Evolving concepts in molecular patholgy", FASEB J. 8:583-592.
Katz et al., 1994, "Serotonin-stimulated aortic endothelial cells secrete a novel T lymphocyte chemotactic and growth factor", J. leukoc. Biol. 55:567-573.
Kokunai et al., 1997, "Induction of differentiation by wild-type p53 gene in a human glioma cell", J. Neuro-oncol. 32:125-133.
Kurabayashi and Yazaki, 1996, "Molecular genetic approach to the pathophysiology of cardiovascular disease", Int. Angiol. 15:187-194.
Libby et al., 1996, "Macrophages and atherosclerotic plaque stability", Curr. Opin. Lipidol. 7:330-335.
Lovejoy et al., 1997, "Animal models and the molecular pathology of cancer", J. Pathol. 181:130-135.
Makela et al., 1994, "A cyclin associated with the CDK-activating kinase MO15", Nature 371:254-257.
Maneiro et al., 1997, "An experimental model to study the cytotoxic effects induced by .beta.-amyloid, histamine, LPS and serum from Alzheimer patients on cultured rat endothelial cells", Methods Find. Exp. Clin. Pharmacol. 19:5-12.
Mendelsohn, 1994, "Applications of interaction traps/two-hybrid systems to biotechnology research", Current Biology 5:482-486.
Mendelsohn, 1992, "Principles of neoplasia" Harrison's Principles of Internal Medicine (McGraw-Hill, Inc., New York) pp. 1814-1826.
Milne et al., 1994, "Phosphorylation of the tumor suppressor protein p53 by mitogen-activated protein kinases", J. Biol. Chem. 269:9253-9260.
Muir, 1997, "Acetylcholine, aging, and Alzheimer's disease", Pharamcol. Biochem. Behav. 56:687-696.
Nakajima et al., 1985, "Dissociated cell culture of cholinergic neurons from nucleus basalis of Meynert and other basal forebrain nuclei", Proc. Natl. Acad. Sci. USA 82:6325-6329.
Nakamura et al., 1995, "Cyclin I: a new cyclin encoded by a gene isolated from human brain", Exp. Cell Res. 221:534-542.
Nevins, 1992, "E2F: a link between the Rb tumor suppressor protein and viral oncoproteins", Science 258:424-429.
Ninomiya-Tsuji et al., 1991, "Cloning of a human cDNA encoding a CDC2-related kinase by complementation of a budding yeast cdc28 mutation", Proc. Natl. Acad. Sci. USA 88:9006-9010.
Oron et al., 1997, "Animal model and in vitro studies of anti neurofilament antibodies mediated neurodegeneration in Alzheimer's disease", J. Neural Transm. Suppl 49:77-84.
Oyasu, 1995, "Epithelial tumours of the lower urinary tract in humans and rodents", Food Chem. Toxicol. 33:747-755.
Padgett et al., 1984, "Splicing of messenger RNA precursors", Ann. Rev. Biochem. 55:1119-1150.
Paigen et al., 1994, "The mouse as a model for human cardiovascular disease and hyperlipidemia", Curr. Opin. Lipidol. 5:258-264.
Polakis, 1997, "The adenomatous polyposis coli (APC) tumor suppressor", Biochem. Biophys. Acta 1332:F127-F147.
Poon and Hunter, 1995, "Dephosphorylation of Cdk2 Thr160 by the cyclin-dependent kinase-interacting phosphatase KAP in the absence of cyclin", Science 270:90-93.
Popovic et al., 1996, "Behavioral and adaptive status in an experime
Nandabalan Krishnan
Schultz Vincent Peter
Yang Meijia
CuraGen Corporation
Degen Nancy
Elrifi Ivor R.
Morency Michel
Schwartzman Robert
LandOfFree
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