Cloning and analysis of the genes involved in the regulation of cell cycle and growth by complementation cloning.

1992 Fiscal Year Final Research Report Summary

• Project/Area Number: 02454537
• Research Category: Grant-in-Aid for General Scientific Research (B)
• Allocation Type: Single-year Grants
• Research Field: 物質生物化学
• Research Institution: Osaka University
• Principal Investigator: NOJIMA Hiroshi Osaka University, Research Institute for Microbial Diseases, Department of Molecular Genetics, Assistant Professor., 微生物病研究所, 助教授 (30156195)
• Co-Investigator(Kenkyū-buntansha): 小野 泰子 大阪大学, 微生物病研究所, 文部技官 (70194602) ; NAGATA Akihisa Tokyo University, Department of Medicene, Assistant, 微生物病研究所, 助手 (50155933) ; OKAYAMA Hiroto Tokyo University, Department of Medicene, Professor, 微生物病研究所, 教授 (40111950) ; OKAZAKI Koei ERATO Okayama Project, Research fellow (70213923)
• Project Period (FY): 1990 – 1992
• Keywords: Complementation / NRK / EGF / signal transduction / S.pombe / cdc mutant / Mlu motif / cAMP

Research Abstract

We have pursued our research project by utilizing two kinds of research systems as described separately as follows;
(1) Using NRK(normal rat kidney) cells: NRK cells are useful because they are transformed reversibly by the addition of EGF and TGF-beta. We have established several mutant strains which are insensitive to the effect of EGF and TGF-beta. Usingthese mutants, we have investigated the signal pathway of EGF and several oncogenes and anchorage dependency.
(2) Using S.pombe cell division cycle (cdc) mutants, cdc2, cdc13 and cdc10: We have cloned and analysed 3 novel human genes that complement both cdc2 and cdc13. DNA sequencing revealed that they encode RNA binding proteins. They seem to complement these mutants by stabilizing and inducing translation of cdc13 gene product. We also cloned 8 kinds of novel genes that complement cdc 10 mutant. DNA sequencing unveiled that two clones encode proteins with two ankyrin motifs and with homologous domains to cdc10 gene product and those of SWI4/SW16 (S.cerevisiae) gene products. One clone was found to be cdc18 itself. One clone (rep1) encode a zinc-finger protein which is required in premeiotic DNA synthesis. One clone (HAC1) was a homologue of ATF/CREB. DNA sequence of the rest of three clones remain to be determined.

Research Products

• [Publications] Kizaka-Kondoh S,Sato K,tamura K,nojuma H, & Okayama H.: "Ralf-1 protein kinase is an integral component of oncogenic signal cascade shared by epidermal growth factor and platelet-derived growth factor," Molecular Cellular Biology. 12. 5078-5086 (1992)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tatsuka M,Mitsui H,Wada M,Nagata A,Nojima H, & Okayama H.: "Elongation factor-alfa is a transformation-susceptibility determinant in BALB/c 3T3 cells." Nature. 359. 333-336 (1992)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tanaka K,Okazaki K,Okazaki N,Ueda T,Sugiyama A,Nojima H, & Okayama H.: "A new cdc gene required for S phase entry of Schizosaccharomyces pombe encodes a protein similar to the cdc10 and SW14 gene products." EMBO Journal. 11. 4923-4932 (1992)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tamura K,Kanaoka Y,Jinno S,Nagata A,Ogiso Y,Shimizu K,Hayakawa T,Nojima H, & Okayama H.: "Cyclin G: a new mammalian cyclin with a potential tyrosine phosphorylation site." Oncogene.
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 野島 博: "遺伝子診断入門" 羊土社(東京), 188 (1992)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yagisawa H, Kambe T, Nojima H: "Cloning of a DNA fragment displaying restriction fragment length polymorphisms between the genomes of spontaneously hypertensive and Wistar-Kyoto rats." J Hypertens. 8(4). 307-313 (1990)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Inoue H, Nojima H, Okayama H: "High-efficiency transformation of Escherichia coli with pladmids." Gene. 96(1). 23-28 (1990)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yagisawa H, Emori Y, Nojima H: "Phospholipase gene display restriction fragment length polymorphism between the genomes of normotensive and hypertensive rats." J Hypertens. 9(11). 303-307 (1991)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Weinman J, Gaspera, BD, Dautigny A, Dinh DP, Wang J, Nojima H, Weinman S: "Developmental regulation of calmodulin gene expression in rat brain skeletal muscle." Cell Regulation. 2(10). 819-826 (1991)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yagisawa H, Tanase H, Nojima H: "Phospholipase C-d gene of the pontaneously hypertensive rat harbours point mutations causing amino acid substitutions in a catalytic domain." J Hypertens. 9(11). 997-1004 (1991)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Katsuya T, Higaki J, Miki T, Kohara H, Yagisawa H, Tanase H, Mikami H, Nojima H, Ogihara T: "Hypotensive effect associated with a phospholipase C-81 gene mutation in the spontaneously hypertensive rat." Biochem Biophys Res Commun. 187(3). 1359-1366 (1992)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Feinberg J, Gaspera BD, Rainteau D, Weinman J, Weinman S, Kaetzel MA, Dedman JR, Lessard JL, Nojima H, Wang J, Huynh TDH, Pepinsky RB, Moss SE, Crumpton MJ: "Calmodulin and annexins in rat small intestine enterocyte: a comparative biochemical and immunocytochemical study." J Cell Biol.
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Masuda A, Kizaka-Kondoh S., Miwatani H, Terada Y, Nojima H, Okayama H: "Signal transduction cascade shared by epidermal growth factor and platelet-derived growth factor is a major pathway for oncogenic transformation in NRK cells." New Biol. 4(5). 489-503 (1992)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kume K, Jinno S, Miwatani H, Kizaka-Kondoh S, Terada Y, Nojima H, Okayama H: "Oncogenic signal-induced ability to enter S phase in the absence of anchorage is the mechanism for the growth of transformed NRK cells in soft agar." New Biol. 4(5). 504-511 (1992)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kizaka-Kondoh S, SatoK, Tamura K, Nojima H, Okayama H: "Raf-1 protein kinase is and integral component of oncogenic signal cascade shared by epidermal growth factor and platelet-derived growth factor." Mol Cell Biol. 12(11). 5078-5086 (1992)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tatsuka M, Mitsui H, Wada M, Nagata A, Nojima H, Okayama H: "Elongation factor-1alpha is a transformation-susceptibility determinant in BALB/c 3T3 cells." Nature. 359. 333-336 (1992)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tanaka K, Okazaki K, Okazaki N, Ueda T, Sugiyama A, Nojima H, Okayama H: "A new cdc gene required for S phase entry of Schizosaccharomyces pombe encodes a protein similar to the cdc10^+ and SWI4 gene products." EMBO J. 11(13). 4923-4932 (1992)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tamura K, Kanaoka Y, Nojima H, Okayama H: Cyclin G: "a new cyclin with a potential tyrosine phosphorylation site." Oncogene.
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nojima H: "Rose of molecular genetics in the understanding of the pathogenesis of hypertension." Gerontology. 36(suppl 1). 31-41 (1990)
  • Description: 「研究成果報告書概要(欧文)」より