1998 Fiscal Year Final Research Report Summary
Intracellular signals of activin-A mediating growtharrest and apoptosis
| Project/Area Number |
09671847
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Morphological basic dentistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
YAMATO Kenji Tokyo Dent.Med.Univ.Faculty of Dentistry Lecturer, 歯学部, 講師 (50174751)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIHARA Tatsuji Natl.Inst.Infect.Dis.Laboratory Chief of Periodontal Diseases, 口腔科学部, 歯周病室室長 (80192251)
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| Project Period (FY) |
1997 – 1998
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| Keywords | activin / G1 arrest / apoptosis / p21^<CID1 / WAF1> / Smad 2 / Smad 7 / WAF1 |
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| Research Abstract |
Activin response is initiated by the binding of activin to a pair of specific receptors, designated as activin type I receptor (ActR-I) and activin type II receptor (ActR-II), leading to activation of ActR-I.The signal is transferred to Smad2/3 through the receptor-kinase mediated phosphorylation of Smads. The phosphorylated Smad2/3 form hetero-oligomers with Smad4, translocate to the nucleus and transactivate genes executing activin effects. Inhibitory Smads such as Smad6 and Smad7 has been reported to inhibit biological activities of TGFfbeta.
In this research project, we investigated the molecular mechanisms by which activin-A induced growth arrest and apoptosis using HS-72 mouse hybridoma cells. The followings are new findings obtained by this study :
1) Activin-signals for growth arrest and apoptosis were mediated through ActR-IB but not ActR-I and overexpression of ActR-I inhibited these activin-effects mediated through ActR-JB.
2) Both activin-induced growth arrest and apoptosis were mediated by phosphorylation of Smad2.
3) Activin-A induced growth arrest by activating p2lCIPl/WAF1 expression.
4) Smad7 was an activin-inducible gene product and negatively regulated activin-induced growth arrest and apoptosis by inhibiting Smad2 phosphorylation.
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[Publications] Muro, M., Koseki, T., Akifusa, S., Kato, S., Kowashi, Y., Ohsaki, Y., Yamato, K., Nishijima, M., Nishihara, T.: "Role of CD14 molecules in internalization of Actinobacillus actinomycetemcomitans by macrophages and subsequent induction of apoptosis." Infect.Immun.65. 1147-1151 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Yamamoto, M., Nishihara, T., KOseki, T., He, T., Yamato, K., Zhang, Y.-J., Nakashima, K., Oda, S.and Ishikawa, I.: "Prevalence of Actinobacillus actinomycetemcomitans serotpes in Japanese patients with periodontitis." J.Periodontal Res.32. 676-681 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Yamato, K., Koseki, T., Ohguchi, M., Kizaki, M., Ikeda, Y., Nishihara, T.: "Activin A induction of cell-cycle arrest involves modulation of cyclin D2 and p21^<CIP1/WAP1> in plasmacytic cells." Mol.Endocrinol.11. 1044-1052 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Akifusa, S., Ohguchi, M., Koseki, T., Nara, K., Semba, I., Yamato, K., Okahashi, N., Moreno, R., Nunez, G., Hanada, N., Takehara, T., and Nishihara, T.: "Increase in Bcl-2 level promoted by CD-40 ligation correlates with inhibition of B-cell apoptosis induced by vacuolar type H^+-ATPase inhibitor." Exp.Cell Res.238. 82-89 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Ueno, H., Kizaki, M., Matsushita, H., Muto, M., Yamato, K., Nishihara, T., Hida, T., Yoshimura, H., Koeffler, H.P.and Ikeda, Y.: "A novel retinoic acid receptor (RAR)-selective antagonist inhibits differentation and apoptosis of HL-60 : implications of RARalpha-mediated signals in myeloid leukemia cells." Leukemia Res.22. 517-525 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Koseki, T., Yamato, K., Ishisaki, A., Hashimoto, O., Sugino, H., Nishihara, T.: "Accumulation of Bc1-X_s in mouse B-cell hybridoma cells during activin A-mediated apoptosis." Cell. Singal. 10. 517-521 (1998)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Ishisaki, A., Yamato, K., Nakao, A., Nonaka, K., Ohguchi, M., ten Dijke, P., Nishihara, T.: "Smad7 is an activin-inducible inhibitor of activin-induced growth arrest and apoptosis in mouse B cells." J.Biol.Chem.273. 24293-24296 (1998)
Description
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[Publications] Hashimoto, O., Yamato, K., Ohguchi, M., Koseki, T., Ishisaki, A., Shoji, H., Nakamura, T., Sugino, H., and Nishihara, T.: "The Role of activin type I receptors in activin A-induced growth arrest and apoptosis in HS-72 B-cell hybridoma cells." Cell. Singal. 10. 743-749 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Ohguchi, M., Yamato, K., Ishihara, U., Koide, M., Okahashi, N., Noguchi, T., T., Kizaki, M., Ikeda, Y., Sugino, H., and Nishihara, T.: "Activin A regulates the production of mature interleukin-1beta and interleukin 1 receptor antagonist in human monocytic cells." J.Interferon Cytokine Res.18. 491-498 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Ohguchi, M., Okahashi, N., Koide, M., Koseki, T., Yamato, K., Noguchi, T., Nishihara.T.: "Exotoxin from Actinobacillus actinomycetemcomitans induces cell cycle arrest in the G2/M phase and apoptosis." Infect.Immun. 66. 5980-5987 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Ishisaki, A., Yamato, K., Hashimoto, S., Nakao, A., Tamaki, K., Nonaka, K., ten Dijke, P., Sugino, H., Nishihara, T.: "Differential inhibition of Smad6 and Amad7 on bone morphogenetic protein-and activin-mediated growth arrest and apoptosis in B cells." J.Biol.Chem.(in press).
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「研究成果報告書概要(欧文)」より
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[Publications] Muto, A., Kizaki, M., Yamato, K., Kamata, M., Ueno, H., Kawai, Y., Ohguchi, M., Nishihara, T., Koeffler, H.P., and Ikeda, Y.: "1,25-Dihydroxyvitamin D3 induces differentiation of retinoic acid-resistant APL cell line (UF-1) associated with expression of p21^<WAP1/CIP1> and" Blood. (in press).
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