Regulation mechanism of cell cycle by differentiation signals

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 13043058
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto Institute of Technology
• Principal Investigator: YAMAGUCHI Masamitsu Kyoto Institute of Technology, Department of Applied Biology, Professor, 繊維学部, 教授 (00182460)
• Co-Investigator(Kenkyū-buntansha): ITOH Masanobu Kyoto Institute of Technology, Department of Applied Biology, Associate Professor, 繊維学部, 助教授 (60221082) ; HIROSE Fumiko University of Hyogo, Graduate School of Life Science, Department of Life Science, Associate Professor, 生命理学研究科, 助教授 (60208882)
• Project Period (FY): 2001 – 2005
• Keywords: Drosophila melanosaster / transription factor / molecular cell biology / DNA replication-related genes / translation initiation factor / chromatin immunoprecipitation assay / cell differentiation / cell proliferation

Research Abstract

The DNA replication-related element-binding factor (DREF) has been suggested to be involved in regulation of DNA replication and proliferation-related genes in Drosophila. Over-expression of DREF induced ectopic DNA synthesis and apoptosis, and inhibited the photoreceptor cell differentiation in eye imaginal discs and adult flies exhibited a severe rough eye phenotype. We used DREF over-expressing fly lines as a tool to screen mutations that modify the rough eye phenotype. We identified 20 lines including eIF4a and skpA gene mutations that suppressed and 6 lines that enhanced the rough eye phenotype when they were heterozygous for the mutations. Since it is reported that eIF4a protein is associated with growth by regulating protein translation, regulation of eIF4a gene expression by DREF would be important for regulation of cell proliferation. SKPa is component of a Drosophila SCF complex that functions in combination with the ubiquitin conjugating enzyme UbcDl. DREF may therefore play roles in regulation of protein metabolism at the onset of cell proliferation.
A yeast one-hybrid screen using three tandem repeats of DRE in dPCNA promoter as the bait allowed isolation of a cDNA encoding Cut, a Drosophila homologue of mammalian CCAAT-displacement protein (CDP)/Cux. Electrophoretic mobility shift assays showed that Cut bound to both DRE. Measurement of dPCNA promoter activity by.transient luciferase expression assays in Drosophila S2 cells after an RNA interference for Cut or DREF showed DREF activates the dPCNA promoter while Cut functions as a repressor. Chromatin immunoprecipitation assays in the presence or absence of 20-hydroxyecdysone further showed both DREF and Cut proteins to be localized in the genomic region containing the dPCNA promoter in S2 cells, especially in the Cut case upon induction of differentiation. These results indicate that Cut functions as a transcriptional repressor of dPCNA gene by binding to the promoter region in the differentiated state, while DREF binds to DRE to promote expression of dPCNA during cell proliferation.

Research Products

• [Journal Article] Complex interference in the eye developmental pathway by Drosophila NF-YA. (2007)
  • Author(s): Yoshioka, Y., Suyari, O., Yamada, M., Ohno, K., Hayashi, Y., Yamaguchi, M.
  • Journal Title: Genesis 45 Pages: 21-31
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Prevalence of full-size P and KP elements in North America populations of Drosophila melanogaster. (2007)
  • Author(s): Itoh, M., Takeuchi, N., Yamaguchi, M., Yamamoto, M., Boussy, I., A.
  • Journal Title: Genetica (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Dynamic Changes in the Subcellular Localization of Drosophila β-Sarcoglycan during the Cell Cycle. (2007)
  • Author(s): Hashimoto, R., Yamaguchi, M.
  • Journal Title: Cell Struct. Funct. (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Complex interference in the eye developmental pathway by Drosophila NF-YA. (2007)
  • Author(s): Yoshioka, Y., Suyari, 0., Yamada, M., Ohno, K., Hayashi, Y., Yamaguchi, M.
  • Journal Title: Genesis 45 Pages: 21-31
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Prevalence of full-size P and KP elements in North America populations of Drosophila melanogaster. (2007)
  • Author(s): Itoh, M., Takeuchi, N., Yamaguchi, M., Yamamoto, M., Boussy, I., A.
  • Journal Title: Genetica (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Dynamic Changes in the Subcellular Localization of Drosophila D-Sarcoglycan during the Cell Cycle. (2007)
  • Author(s): Hashimoto, R., Yamaguchi, M.
  • Journal Title: Cell Struct. Funct. (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Drosophila Damaged DNA Binding Protein 1 contributes to genome stability in somatic cells. (2006)
  • Author(s): Shimanouchi, K., Takata, K., Yamaguchi, M., Murakami, S., Ishikawa, G., Takeuchi, R., Kanai, Y., Ruike, T., Nakamura, R., Abe, Y., Sakaguchi, K.
  • Journal Title: J. Biochem. 139 Pages: 51-58
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Antagonistic regulation of the Drosophila PCNA gene promoter by DREF and Cut. (2006)
  • Author(s): Seto, H., Hayashi, Y., Kwon, E., Taguchi, O., Yamaguchi, M.
  • Journal Title: Genes to Cells 11 Pages: 499-512
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Genetic link between β-sarcoglycan and the Egfr signaling pathway. (2006)
  • Author(s): Hashimoto, R., Yamaguchi, M.
  • Journal Title: Biochem. Biophys. Res. Commun. 348 Pages: 212-221
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Drosophila Distal-less negatively regulates dDREF by inhibiting its DNA binding activity. (2006)
  • Author(s): Hayashi, Y., Kato, M., Seto, H., Yamaguchi, M.
  • Journal Title: Biochim. Biophys. Acta. 1759 Pages: 359-366
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identification of the Drosophila skpA gene as a novel target of the transcription factor DREF. (2006)
  • Author(s): Thao, D.T.P., Ida, H., Yoshida, H., Yamaguchi, M.
  • Journal Title: Exp. Cell Res. 312 Pages: 3641-3650
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Antagonistic regulation of the Drosophila PCNA gene promoter by DREF and Cut. (2006)
  • Author(s): Seto, H., Hayashi, Y., Kwon, E., Taguchi, 0., Yamaguchi, M.
  • Journal Title: Genes to Cells 11 Pages: 499-512
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Genetic link between ^-sarcoglycan and the Egfr signaling pathway. (2006)
  • Author(s): Hashimoto, R., Yamaguchi, M.
  • Journal Title: Biochem. Biophys. Res. Commun. 348 Pages: 212-221
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Alternative splicing regulates the transcriptional activity of Drosophila heat shock transcription factor in response to heat/cold stress. (2005)
  • Author(s): Fujikake, N., Nagai, Y., Popiel H.A., Kano, H., Yamaguchi, M., Toda, T.
  • Journal Title: FEBS letter 579 Pages: 3842-3848
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Transcriptional regulation of the Drosophila orc2 gene by the DREF pathway. (2005)
  • Author(s): Okudaira, K., Ohno, K., Yoshida, H., Asano, M., Hirose, F., Yamaguchi, M.
  • Journal Title: Biochim. Biophys. Acta. 1732 Pages: 23-30
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Transcriptional regulation of the Drosophila orc2 gene by the DREF pathway. (2005)
  • Author(s): Okudaira, K., Ohno, K., Yoshida, H., Asano, M., Hirose, F., Yamaguchi, M.
  • Journal Title: Biochem. Biophys. Acta. 1732 Pages: 23-30
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Redox regulation of DNA binding activity of DREF in Drosophila. (2004)
  • Author(s): Choi, T.-Y., Park, S.Y., Kang, H.-S., Cheong, J.-H., Kim, H.-D., Lee, B.L., Hirose, F., Yamaguchi, M., Yoo, M.-A.
  • Journal Title: Biochem. J. 378 Pages: 833-838
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Drosophila damaged DNA binding protein 1 (D-DDB1) is an essential factor for development. (2004)
  • Author(s): Takata, K., Yoshida, H., Yamaguchi, M., Sakaguchi, K.
  • Journal Title: Genetics 168 Pages: 855-865
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Genetic Link between p53 and genes required for formation of the zonula adeherens junction. (2004)
  • Author(s): Yamaguchi, M., Hirose, F., Inoue Y.H., Ohno, K., Yoshida, H., Hayashi, Y., Deak, P., Matsukage, A.
  • Journal Title: Cancer Sci. 95 Pages: 436-441
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Phenotypic stability of the P-M system in wild populations of Drosophila melanogaster. (2004)
  • Author(s): Itoh, M., Fukui, T., Kitamura, M., Uenoyama, T., Watada, M., Yamaguchi, M.
  • Journal Title: Genes Genet. Syst. 79 Pages: 9-18
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Transcriptional regulation of the Drosophila caudal homeobox gene by the DRE/DREF system. (2004)
  • Author(s): Choi, Y.-J., Choi, T.-Y., Yamaguchi, M., Matsukage, A., Kim.Y.-S., Yoo, M.-A.
  • Journal Title: Nucleic Acids Res. 32 Pages: 3734-3742
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] DREF is required for EGFR signaling during Drosophila wing vein development. (2004)
  • Author(s): Yoshida, H., Kwon, E., Hirose, F., Otsuki, K., Yamada, M., Yamaguchi, M.
  • Journal Title: Genes to Cells 9 Pages: 935-944
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Armadillo/ Pangolin regulates PCNA and DREF promoter activities. (2004)
  • Author(s): Kwon E., Hayashi, Y., Otsuki, K., Hirose, F., Nishida, Y., Yoo, M.-A., Yamaguchi, M.
  • Journal Title: Biochem. Biophys. Acta. 1679 Pages: 256-262
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Damaged DNA binding protein 1 in Drosophila defense reactions. (2004)
  • Author(s): Takata, K., Shimanouchi, K., Yamaguchi, M., Murakami, S., Ishikawa, G., Takeuchi, R., Kanai, Y., Ruike, T., Nakamura, R., Abe, Y., Sakaguchi, K.
  • Journal Title: Biochem. Biophys. Res. Commun. 323 Pages: 1024-1031
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Characterization of dRFX2, a novel RFX family protein in Drosophila. (2004)
  • Author(s): Otsuki, K., Hayashi, Y., Kato, M., Yoshida, H., Yamaguchi, M.
  • Journal Title: Nucleic Acids Res. 32 Pages: 5636-5648
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Damaged DNA binding protein 1 in Drosophila defense reactions. (2004)
  • Author(s): Takata, K., Shimanouchi, K., Yamaguchi, M., Murakami, S., Ishikawa, G., Takeuchi, R., Kanai, Y., Ruike, T., Nakamura, R., Abe, Y., Sakaguchi, K.
  • Journal Title: Biochem. Biophys. Res. Commun. 1024-1031
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Transcription control of a gene for Drosophila transcription factor, DREF by DRE and cis-elements conserved between Drosophila melanogaster and virilis. (2003)
  • Author(s): Kwon, E., Seto, H., Hirose, F., Ohshima, N., Takahashi, Y., Nishida, Y., Yamaguchi, M.
  • Journal Title: Gene 309 Pages: 101-116
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Prevention of polyglutamine oligomerization and neurodegeneration by the peptide inhibitor QBP1 in Drosophila. (2003)
  • Author(s): Nagai, Y., Fujikake, N., Ohno, K., Higashiyama, H., Popiel, H.A., Rahadian, J., Yamaguchi, M., Strittmatter, W.J., Burke, J.R., Toda, T.
  • Journal Title: Hum. Mol. Genet. 12 Pages: 1253-1260
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Tandem duplication of alkaline phosphatase genes and polymorphism in the intergenic sequence in Bombyx mori. (2003)
  • Author(s): Itoh, M., Inoue, T., Kanamori, Y., Nishida, S., Yamaguchi, M.
  • Journal Title: Mol. Gen. Genomics 270 Pages: 114-120
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Prevention of poly glutamine oligomerization and neurodegeneration by the peptide inhibitor QBP1 in Drosophila. (2003)
  • Author(s): Nagai, Y., Fujikake, N., Ohno, K., Higashiyama, H., Popiel, H.A., Rahadian, J., Yamaguchi, M., Strittmatter, W.J., Burke, J.R., Toda, T.
  • Journal Title: Hum. Mol. Genet 12 Pages: 1253-1260
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification of ter94, Drosophila VCP, as a modulator of polyglutamine-induced neurodegeneration. (2002)
  • Author(s): Higashiyama, H., Hirose, F., Yamaguchi, M., Inoue, Y.H., Fujikake, N., Matsukage, A., Kakizuka, A.
  • Journal Title: Cell Death and Differentiation 9 Pages: 264-273
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The Caudal homeodomain protein activates Drosophila E2F gene expression. (2002)
  • Author(s): Hwang, M.-S., Kim, Y.-S., Choi, N.-H., Park, J.-H., Oh, E.-J., Kwon, E.-J., Yamaguchi, M., Yoo, M.-A.
  • Journal Title: Nucleic Acids Res. 30 Pages: 5029-5035
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Drosophila Mi-2 negatively regulates dDREF by inhibiting its DNA-binding activity. (2002)
  • Author(s): Hirose, F., Ohshima, N., Kwon, E.-J., Yoshida, H., Yamaguchi, M.
  • Journal Title: Mol. Cell. Biol. 22 Pages: 5182-5193
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Transcriptional regulation of the Drosophila raf proto-oncogene by the transcription factor dE2F. (2001)
  • Author(s): Kwon, E.-J., Oh, E.-J., Kim, Y.-S., Hirose, F., Ohno, K., Nishida, Y., Matsukage, A., Yamaguchi, M., Yoo.M.-A.
  • Journal Title: Nucleic Acids Res. 29 Pages: 1808-1814
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Ectopic expression of BEAF32A in the Drosophila eye imaginal disc inhibits differentiation of photoreceptor cells and induces apoptosis. (2001)
  • Author(s): Yamaguchi, M., Yoshida, H., Hirose, F., Inoue, Y.H, Hayashi, Y., Yamagishi, M., Nishi, Y., Tamai, K., Sakaguchi, K., Matsukage, A.
  • Journal Title: Chromosoma 110 Pages: 313-321
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Overexpression of DREF in the Drosophila wing imaginal disc induces apoptosis and a notching wing phenotype. (2001)
  • Author(s): Yoshida, H., Inoue, Y.H., Hirose, F., Sakaguchi, K., Matsukage, A., Yamaguchi, M.
  • Journal Title: Genes to Cells 6 Pages: 877-886
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Ectopic expression of DREF induces DNA synthesis, apoptosis and unusual morphogenesis in the Drosophila eye imaginal disc : possible interaction with Plycomb and trithorax group proteins. (2001)
  • Author(s): Hirose, F., Ohshima, N., Shiraki, M., Inoue, Y.H., Taguchi, O., Nishi, Y., Matsukage, A., Yamaguchi, M.
  • Journal Title: Mol. Cell. Biol. 21 Pages: 7231-7242
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Drosophila mitochondrial transcription factor A : Characterization of its cDNA and expression pattern during development. (2001)
  • Author(s): Takata, K., Yoshida, H., Hirose, F., Yamaguchi, M., Kai, M., Oshige, M., Sakimoto, I., Koiwai, O., Sakaguchi, K.
  • Journal Title: Biochem. Biophys. Res. Commun. 287 Pages: 474-483
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Nearest neighbor analysis of MCM protein complexes in Drosophila melanogaster. (2001)
  • Author(s): Crevel, G., Ivetic, A., Ohno, K., Yamaguchi, M., Cotterill, S.
  • Journal Title: Nucleic Acids Res. 29 Pages: 4834-4842
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Ectopic expression of BEAF32A in the Drosophila eye imaginal disc inhibits differentiation of photoreceptor cells and induces apoptosis. (2001)
  • Author(s): Yamaguchi, M., Yoshida, H., Hirose, F., Inoue, Y.H, Hayashi, Y., Yamagishi, M., Nishi, Y., Tamai, K., Sakaguchi, K., Matsukage, A.
  • Journal Title: Chromosoma. 110 Pages: 313-321
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Ectopic expression of DREF induces DNA synthesis, apoptosis and unusual morphogenesis in the Drosophila eye imaginal disc : possible interaction with Plycomb and trithorax group proteins. (2001)
  • Author(s): Hirose, F., Ohshima, N., Shiraki, M., Inoue, Y.H., Taguchi, 0.Nishi, Y., Matsukage, A., Yamaguchi, M.
  • Journal Title: Mol. Cell. Biol. 21 Pages: 7231-7242
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Drosophila mitochondrial transcription factor A : Characterization of its cDNA and expression pattern during development. (2001)
  • Author(s): Takata, K., Yoshida, H., Hirose, F., Yamaguchi, M., Kai, M., Oshige, M., Sakimoto, I., Koiwai, 0., Sakaguchi, K.
  • Journal Title: Biochem. Biophys. Res. Commun. 287 Pages: 474-483
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Nearest neighbour analysis of MCM protein complexes in Drosophila melanogaster. (2001)
  • Author(s): Crevel, G., Ivetic, A., Ohno, K., Yamaguchi, M., Cotterill, S.
  • Journal Title: Nucleic Acids Res. 29 Pages: 4834-4842
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] 増殖因子下流でのDNA複製の制御.ゲノムの複製と分配(松影昭夫・正井久雄編) (2002)
  • Author(s): 山口 政光
  • Total Pages: 9
  • Publisher: シュプリンガーフェアラーク東京
  • Description: 「研究成果報告書概要(和文)」より
• [Book] 増殖関連遺伝子の制御機構.発生における細胞増殖制御(竹内隆・岸本健雄編) (2002)
  • Author(s): 山口 政光
  • Total Pages: 9
  • Publisher: シュプリンガーフェアラーク東京
  • Description: 「研究成果報告書概要(和文)」より