Regulation of hTERT gene expression

• Project/Area Number: 23501258
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Carcinogenesis
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: NAKAMURA Masataka 東京医科歯科大学, 医歯学研究支援センター, 教授 (30180392)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: HTAL-1 / Tax / hTERT / KLF2 / HTLV-1 / DNAメチル化

Research Abstract

T lymphocytes are exceptional in that they express a telomerase elongation enzyme (hTERT), though they are normal. hTERT expression contributes to long-life memory T lymphocytes via senescence prevention. We examined molecular mechanism of hTERT gene expression in human T cells. The hTERT promoter contains a DNA element which regulates hTERT expression. The transcription factor KLF2 binds to the element, resulting in repression of hTERT expression in growth resting cells. In growing cells, KLF2 is not associated with the element. DNA methylation of the element is seen in T leukemic T cells. DNA methylated element can not bind to KLF2, constitutively expressing hTERT.

Research Products

• [Journal Article] Anti-tumor effects of inactivated Sendai virus particles with an IL-2 gene on angiosarcoma (2013)
  • Author(s): Takehara Y, Satoh T, Nishizawa A, Saeki K, Nakamura M, Matsuzawa M, Kaneda Y, Katayama I, Yokozeki H
  • Journal Title: Clin. Immunol Volume: 149 Pages: 1-10
  • Peer Reviewed
• [Journal Article] CD19 target-engineered T-cells accumulate at tumor lesions in human B-cell lymphoma xenograft mouse models (2013)
  • Author(s): Tsukahara T, Ohmine K, Yamamoto C, Uchibori R, Ido H, Teruya T, Urabe M, Mizukami H, Kume A, Nakamura, M, Mineno J, Takesako K, Riviere I, Sadelain M, Brentjens R, Ozawa K
  • Journal Title: Biophy. Biochem. Res. Commun Volume: 438 Pages: 84-89
  • Peer Reviewed
• [Journal Article] Anti-inflammatory role of PGD2 in acute lung inflammation and therapeutic application of its signal enhancement (2013)
  • Author(s): Murata T, Aritake K, Tsubosaka Y, Maruyama T, Nakagawa T, Hori M, Hirai H, Nakamura M, Narumiya S, Urade Y, Ozaki H
  • Journal Title: Pro. Natl. Acad. Sci. USA Volume: 110 Pages: 5205-5210
  • Peer Reviewed
• [Journal Article] Mast cell matyration is driven via a group III phospholipase A_2-prostaglandin D_2-DP1 receptor paracrine axis (2013)
  • Author(s): Taketomi Y, Ueno N, Kojima T, Sato H, Murse R, Yamamoto K, Tanaka S, Sakanaka M, Nakamura M, Hishito Y, Kawana M, Kambe N, Ikeda K, Taguchi R, Nakamizo S, Kabashima K, Gelb M H, Arita M, Yokomizo T, Nakamura M, Watanabe K, Hirai H, Nakamura M, Okayama Y, Ra C, Aritake K, Urade Y, Morimoto K, Sugimoto Y, Shimizu T, Narumiya S, Hara S, Murakami M
  • Journal Title: Nature Immunol Volume: 14 Pages: 554-563
  • Peer Reviewed
• [Journal Article] Failure in activation of the canonical NF-кB pathway by human T-cell leukemia virus type 1 Tax in non-hematopoietic cell lines (2013)
  • Author(s): Mizukoshi T, Komori H, Mizuguchi M, Abdelaziz H, Hara T, Higuchi M, Tanaka Y, Ohara Y, Funato N, Fujii M, Nakamura M
  • Journal Title: Virology Volume: 443 Pages: 226-235
  • Peer Reviewed
• [Journal Article] Mast cell matyration is driven via a group III phospholipase A2-prostaglandin D2-DP1 receptor paracrine axis. (2013)
  • Author(s): Taketomi, Y., Ueno, N., Kojima, T., Sato, H., Murse, R., Yamamoto, K., Tanaka, S., Sakanaka, M., Nakamura, M., Hishito, Y., Kawana, M., Kambe N., Ikeda, K., Taguchi, R., Nakamizo, S., Kabashima, K., Gelb, M. H., Arita, M., Yokomizo, T., Nakamura, M., Watanabe, K., Hirai, H., Nakamura, M., Okayama, Y., Ra C. et al.
  • Journal Title: Nature Immunol. Volume: 14 Pages: 554-563
  • Peer Reviewed
• [Journal Article] Failure in activation of the NF-κB pathway by human T-cell leukemia virus type 1 (HTLV-1) Tax in non-hematopoietic cell lines. (2013)
  • Author(s): Mizukoshi , T., Komori, H., Mizuguchi, M., Abdelaziz,, H., Hara, T., Higuchi, M., Tanaka, Y., Ohara, Y., Funato, N., Fujii,, M. & Nakamura., M.
  • Journal Title: Virology Volume: 443 Pages: 226-235
  • Peer Reviewed
• [Journal Article] Anti-inflammatory role of PGD2 in acute lung inflammation and therapeutic application of its signal enhancement (2013)
  • Author(s): Murata T, Aritake K, Tsubosaka Y, Maruyama T, Nakagawa T, Hori M, Hirai H, Nakamura M, Narumiya S, Urade Y, Ozaki H
  • Journal Title: Proc Natl Acad Sci U S A Volume: 110(13) Issue: 13 Pages: 5205-5210
  • DOI: 10.1073/pnas.1218091110
  • Peer Reviewed
• [Journal Article] Mast cell maturation is driven via a novel group III phospholipase A2-prostaglandin D2-DP1 receptor paracrine axis. (2013)
  • Author(s): Taketomi, Y., Morimoto, K., Murakami, M., et al., 他30名
  • Journal Title: Nature Immunol. Volume: (印刷中) Issue: 6 Pages: 554-63
  • DOI: 10.1038/ni.2586
  • Peer Reviewed
• [Journal Article] Failure in activation of the NF-κB pathway by human T-cell leukemia virus type 1 (HTLV-1) Tax in non-hematopoietic cell lines. (2013)
  • Author(s): Mizukoshi, T.
  • Journal Title: Virology Volume: In press
• [Journal Article] CRTH2 is a critical regulator of neutrophil migration and resistance to polymicrobial sepsis (2012)
  • Author(s): Ishii M, Asano K, Namkoong H, Tasaka S, Mizoguchi K, Asami T, Kamata H, Kimizuka Y, Fujiwara H, Funatsu Y, Kagawa S, Miyata J, Ishii K, Nakamura M, Hirai H, Nagata K, Kunkel SL, Hasegawa N, Betsuyaku T
  • Journal Title: J Immunol Volume: 188 Pages: 5655-5664
  • Peer Reviewed
• [Journal Article] PGD2-CRTH-2 pathway promotes tubulointestitial fibrosis (2012)
  • Author(s): Ito H, Yan X, Nagata N, Aritake K, Katsumata Y, Matsuhashi T, Nakamura M, Hirai H, Urade Y, Asano K, Kubo M, Utsunomiya Y, Hosoya Y, Fukuda K, Sano M
  • Journal Title: J. Am. Soc. Nephrol Volume: 23 Pages: 1797-1809
  • Peer Reviewed
• [Journal Article] CRTH2 is a critical regulator of neutrophil migration and resistance to polymicrobial sepsis. (2012)
  • Author(s): Ishii, M.
  • Journal Title: J. Immunol. Volume: 188 Issue: 11 Pages: 5655-5664
  • DOI: 10.4049/jimmunol.1102330
  • Peer Reviewed
• [Journal Article] Lipocalin-type prostaglandin D2 synthase promotes renal interstitial fibrosis via Th2 lymphocyte activation in unilateral ureteral obstruction. (2012)
  • Author(s): Hideyuki Ito
  • Journal Title: J Am Soc Nephrol Volume: 23(11) Issue: 11 Pages: 1797-809
  • DOI: 10.1681/asn.2012020126
  • Peer Reviewed
• [Journal Article] Distinct roles of prostaglandin D2 receptors in chronic skin inflammation (2011)
  • Author(s): Matsushima Y, Satoh T, Yamamoto Y, Nakamura M, Yokozeki H
  • Journal Title: Mol. Immunol Volume: 49 Pages: 304-310
  • Peer Reviewed
• [Journal Article] Dual functions of prostaglandin D in contact hypersensitivity through DP and CRTH2 (2011)
  • Author(s): Yamamoto Y, Satoh T, Otan S, Aritake K, Urade Y, Narumiya S, Nakamura M, Yokozeki H
  • Journal Title: Amer. J. Pathol Volume: 179 Pages: 302-314
  • Peer Reviewed
• [Journal Article] Chitin particles induce size-dependent but carbonhydrate-independent innate eosinophilia (2011)
  • Author(s): Kogiso M, Nishiyama A, Shinohara T, Nakamura M, Mizoguchi E, Misawa Y, Guinet E, Nouri-Shirazi M, Dorey C.K, Henriksen R.A, Shibata Y
  • Journal Title: J. Leuckocyte Biol Volume: 90 Pages: 167-176
  • Peer Reviewed
• [Journal Article] Reevaluation of quantitative flow cytometric analysis for TLR2 on monocytes using F(ab’)2 fragments of monoclonal antibodies. (2011)
  • Author(s): Oba, R.
  • Journal Title: Cytometry Volume: 79A Pages: 247-255
  • Peer Reviewed
• [Journal Article] Size-dependent induction of eosinophilia and alternative macrophage activation by chitin (2011)
  • Author(s): Kogiso, M.
  • Journal Title: J. Leuckocyte Biol. Volume: 90 Pages: 167-176
  • Peer Reviewed
• [Journal Article] Reciprocal functions of prostaglandin D in contact hypersensitivity through DP and CRTH2. (2011)
  • Author(s): Yamamoto, Y.
  • Journal Title: Amer. J. Pathol. Volume: 179 Pages: 302-314
  • Peer Reviewed
• [Journal Article] Distinct roles of prostaglandin D2 receptors in chronic skin inflammation. (2011)
  • Author(s): Matsushima, Y.
  • Journal Title: Mol. Immunol. Volume: 49 Pages: 304-310
  • Peer Reviewed
• [Presentation] CpG methylation abrogates KLF2-mediated transcriptional repression of telomerase in human T cells (2013)
  • Author(s): Hara T, Nakamura M
  • Organizer: Annual Meeting 2013
  • Place of Presentation: Washington, USA
• [Presentation] Prostaglandin D2 receptor CRTH2 : Discovery to function (2013)
  • Author(s): Nakamura M
  • Organizer: 2013 Shanhai symposium on polyunsaturated fatty acids and metabolism
  • Place of Presentation: Shanghai, China
• [Presentation] Regulation of hTERT transcription by the transcription factor KLF2 and DNA methylation in human T cells (2013)
  • Author(s): Nakamura M, Hara T
  • Organizer: 38^<th> FEBS Congress
  • Place of Presentation: St.Petersburg, Russia
• [Presentation] HTLV-1 Tax activated NF-□B is involved in both cell growth and death (2013)
  • Author(s): Mizuguchi M, Higuchi M, Fujii M. Nakamura M
  • Organizer: 16th International Conference on Human Retrovirology : HTLV and Related Viruses
  • Place of Presentation: Montreal, Canada
• [Presentation] CpG methylation abrogates KLF2-mediated transcriptional repression of telomerase in human T cells. (2013)
  • Author(s): Hara T, Nakamura M.
  • Organizer: Annual Meeting 2013
  • Place of Presentation: Washington, USA
• [Presentation] Prostaglandin D2 receptor CRTH2: Discovery to function. (2013)
  • Author(s): Nakamura M.
  • Organizer: 2013 Shanhai symposium on polyunsaturated fatty acids and metabolism
  • Place of Presentation: Shanghai, China
  • Invited
• [Presentation] HTLV-1 Tax activated NF-κB is involved in both cell growth and death. (2013)
  • Author(s): Mizuguchi M, Higuchi M, Fujii M. Nakamura M.
  • Organizer: 16th International Conference on Human Retrovirology: HTLV and Related Viruses
  • Place of Presentation: Montreal, Canada
• [Presentation] DNA methylation is associated with constitutive expression of human telomerase in T leukemia cells (2012)
  • Author(s): Nakamura M
  • Organizer: IGBMC Chromatin : from Structure to Epigenetics Conference
  • Place of Presentation: Strasbourg, France
• [Presentation] Epigenetic modulation of hTERT expression in human T leukemia cell lines (2012)
  • Author(s): Hara T, Nakamura M
  • Organizer: ICC on Epigenetics in Lymphocyte Biology and Disease
  • Place of Presentation: Barcelona, Spain
• [Presentation] DNA methylation is associated with constitutive expression of human telomerase in T leukemia cells. (2012)
  • Author(s): Nakamura, M.
  • Organizer: IGBMC Chromatin: from Structure to Epigenetics Conference
  • Place of Presentation: Strasbourg, France
• [Presentation] Epigenetic modulation of hTERT expression in human T leukemia cell lines. (2012)
  • Author(s): Hara, T.
  • Organizer: ICC on Epigenetics in Lymphocyte Biology and Disease
  • Place of Presentation: Barcelona, Spain
• [Presentation] Epigenetic modulation of telomerase gene transcription in human T cell leukemia (2011)
  • Author(s): Nakamura M, Hara T
  • Organizer: The 39th Meeting of the ISOBM
  • Place of Presentation: Florence, Italy
• [Presentation] HTLV-1 Taxによる細胞の生死制御機構の解析 (2011)
  • Author(s): 水口 真理子
  • Organizer: 第70回 日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 成人Ｔ細胞白血病ウイルスTaxはREF52細胞では NF-κBのcanonical pathwayを活性化しない (2011)
  • Author(s): 水越 てるみ
  • Organizer: 第70回 日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] HTLV-1 TaxはNF-κB経路を介して細胞死を誘導する.
  • Author(s): 水口 真理子
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] 非血球細胞でのHTLV-1 TaxによるOX40リガンド・プロモーターのNF-κBサイトの不活性化.
  • Author(s): 水越 てるみ
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Differential effects of HTLV-1 Tax on cell fate
  • Author(s): Mizuguchi, M.
  • Organizer: International Union of Microbiological Societies Congresses 2011
  • Place of Presentation: Sapporo
• [Presentation] Epigenetic modulation of telomerase gene transcription in human T cell leukemia
  • Author(s): Nakamura, M.
  • Organizer: The 39th Meeting of the ISOBM
  • Place of Presentation: Florence
• [Book] Roles of HTLV-1 Tax in leukemogenesis of human T-cells. T-cell leukemia (2011)
  • Author(s): Mizuguchi M, Hara T, Nakamura M
  • Publisher: InTech Press, Croatia
• [Book] T-Cell Leukemia (2011)
  • Author(s): Mizuguchi, M.
  • Publisher: Intech