Elucidation of the immune-related genes regulated by ZFAT

• Project/Area Number: 17390101
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human genetics
• Research Institution: Fukuoka University (2006-2008); Research Institute, International Medical Center of Japan (2005)
• Principal Investigator: SHIRASAWA Senji Fukuoka University, 医学部, 教授 (10253535)
• Project Period (FY): 2005 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥16,400,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥2,100,000); Fiscal Year 2008: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2007: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2006: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2005: ¥3,800,000 (Direct Cost: ¥3,800,000)
• Keywords: 自己免疫性甲状腺疾患(AITD) / ZFAT / 転写因子 / ネットワーク / ChIP / 発現アレイ解析 / モノクロナール抗体 / B細胞 / モノクローナル抗体 / 遺伝子改変マウス / SNP / 相関解析

Research Abstract

ZFAT遺伝子は魚類からヒトに至るまで高度に保存された遺伝子であり、発生初期に不可欠な遺伝子であることが明らかとなった。ZFATは正常T,B細胞および白血病細胞株で発現しており、ZFAT機能解析からアポトーシス制御機構に重要な役割を果たしていることが明らかとなった。ZFAT-DNA相互作用解析では、網羅的な基礎データの創出を行い、ZFATの転写制御に関するネットワーク解明への基盤を構築した。

Research Products

• [Journal Article] ZFAT is an antiapoptotic molecule and critical for cell survival in MOLT-4 cells (2009)
  • Author(s): Fujimoto T, Doi K, Koyanagi M, Tsunoda T, Takashima Y, Yoshida Y, Sasazuki T, Shirasawa S.
  • Journal Title: FEBS Lett. 583(3) Pages: 568-72
  • Peer Reviewed
• [Journal Article] Functional Analysis of ZFAT through Specific siRNA against ZFAT in Ba/F3 cell Line (2008)
  • Author(s): Koyanagi M, Doi K, Fujimoto T, Tsunoda T, Takashima Y, Shirasawa S.
  • Journal Title: Med.Bull.Fukuoka univ. 35(4) Pages: 187-191
  • Peer Reviewed
• [Journal Article] ZFAT expression in B and T lymphocytes and identification of ZFAT-regulated genes (2008)
  • Author(s): 0Koyanagi M, Nakabayashi K, Fujimoto T, Gu N, Baba I, Takashima Y, Doi K, Harada H, Kato N, Sasazuki T, Shirasawa S.
  • Journal Title: Genomics 91(5) Pages: 451-7
  • Peer Reviewed
• [Journal Article] Sensitization to the lysosomal cell death pathway by oncogene-induced down-regulation of lysosome-associated membrane proteins 1 and 2. (2008)
  • Author(s): Fehrenbacher N.
  • Journal Title: Cancer Res. 68(16) Pages: 6623-6633
  • Peer Reviewed
• [Journal Article] TATA box-binding protein-associated factor 12 is important for RAS-induced transformation properties of colorectal cancer cells. (2008)
  • Author(s): Voulgari A.
  • Journal Title: Mol. Cancer Res. 6(6) Pages: 1071-1083
  • Peer Reviewed
• [Journal Article] Activated kRas protects colon cancer cells from cucurbitacin-induced apoptosis : the role of p53 and p21. (2008)
  • Author(s): Escandell JM.
  • Journal Title: Biochem. Pharmacol. 76(2) Pages: 198-207
  • Peer Reviewed
• [Journal Article] Ras promotes growth by alternative splicing-mediated inactivation of the KLF6 tumor suppressor in hepatocellular carcinoma. (2008)
  • Author(s): Yea S.
  • Journal Title: Gastroenterology 134(5) Pages: 1521-1531
  • Peer Reviewed
• [Journal Article] ZFAT expression in B and T lymphocytes and identification of ZFAT-regulated genes. (2008)
  • Author(s): Koyanagi M.
  • Journal Title: Genomics 91(5) Pages: 451-457
  • Peer Reviewed
• [Journal Article] HDAC2 deficiency sensitizes colon cancer cells to TNFalpha-induced apoptosis through inhibition of NF-kappaB activity. (2008)
  • Author(s): Kaler P.
  • Journal Title: Exp. Cell Res. 314(7) Pages: 1507-1518
  • Peer Reviewed
• [Journal Article] Search for type 2 diabetes susceptibility genes on chromosomes 1q, 3q and 12q. (2008)
  • Author(s): Takeuchi F.
  • Journal Title: J. Hum. Genet. 53(4) Pages: 314-324
  • Peer Reviewed
• [Journal Article] Low-dose metronomic cyclophosphamide treatment mediates ischemia-dependent K-ras mutation in colorectal carcinoma xenografts. (2008)
  • Author(s): Shahrzad S.
  • Journal Title: Oncogene 27(26) Pages: 3729-3738
  • Peer Reviewed
• [Journal Article] ZFAT expression in B and T lymphocytes and identification of ZFAT-regulated genes (2008)
  • Author(s): Koyanagi M.
  • Journal Title: Genomics (In press)
  • Peer Reviewed
• [Journal Article] HDAC2 deficiency sensitizes colon cancer cells to TNFalpha-induced apoptosis through inhibition of NF-kappaB activity (2008)
  • Author(s): Kaler P.
  • Journal Title: Exp.Cell Res (In press)
  • Peer Reviewed
• [Journal Article] Search for type 2 diabetes susceptibility genes on chromosomes 1q, 3q and 12q (2008)
  • Author(s): Takeuchi F.
  • Journal Title: J.Hum.Genet (In press)
  • Peer Reviewed
• [Journal Article] Low-dose metronomic cyc!ophosphamide treatment mediates ischemia-dependent K-ras mutation in colorectal carcinoma xenografts (2008)
  • Author(s): Shahrzad S.
  • Journal Title: Oncogene (In press)
  • Peer Reviewed
• [Journal Article] Analysis of KRAP expression and localization and genes regulated by KRAP in a human colon cancer cell line (2007)
  • Author(s): Fujimoto T.
  • Journal Title: J.Hum.Genet 52(12) Pages: 978-984
  • Peer Reviewed
• [Journal Article] Histone Deacetylase Inhibitors Induce Cell Death Selectively in Cells That Harbor Activated kRasV12: The Role of Signal Transducers and Activators of Transcription 1 and p21 (2007)
  • Author(s): Klampfer L.
  • Journal Title: Cancer Res 67(18) Pages: 8477-8485
  • Peer Reviewed
• [Journal Article] Acquisition of anoikis resistance promotes the emergence of oncogenicK-ras mutations in colorectal cancer cells and stimulates their tumorigenicity in vivo (2007)
  • Author(s): Derouet M.
  • Journal Title: Neoplasia 9(7) Pages: 536-545
  • Peer Reviewed
• [Journal Article] Transcriptional control of the human high mobility group A1 gene:Basal and oncogenic ras-regulated expression (2007)
  • Author(s): Cleynen I.
  • Journal Title: Cancer Res 67(10) Pages: 4620-4629
  • Peer Reviewed
• [Journal Article] Search of type 2 diabetes susceptibility gene on chromosome 20q (2007)
  • Author(s): Takeuchi F.
  • Journal Title: Biochem.Biophys.Res.Commun 357(4) Pages: 1100-1106
  • Peer Reviewed
• [Journal Article] Quercetin mediates preferential degradation of oncogenic Ras and causes autophagy in Ha-RAS transformed human colon cells (2007)
  • Author(s): Psahoulia FH.
  • Journal Title: Carcinogenesis 28(5) Pages: 1021-1031
  • Peer Reviewed
• [Journal Article] STAT1-independent inhibition of cyclooxygenase-2 expression by IFNgamma; a common pathway of IFNgamma-mediated gene repression but not gene activation (2007)
  • Author(s): Klampfer L.
  • Journal Title: Oncogene 26(14) Pages: 2071-2081
  • Peer Reviewed
• [Journal Article] Quercetin mediates perferential degradation of oncogenic Ras and causes autophagy in Ha-RAS transformed human colon cells. (2007)
  • Author(s): Psahoulia FH et al.
  • Journal Title: Carcinogenesis (In press)
• [Journal Article] STAT1-independent inhibition of cyclooxygenase-2 expression by IFNgamma; a common pathway of IFNgamma-mediated gene repression but not gene activation. (2007)
  • Author(s): Klampfer L et al.
  • Journal Title: Oncogene (In press)
• [Journal Article] Survivin depletion preferentially reduces the survival of activated K-Ras-transformed cells. (2007)
  • Author(s): Sarthy AV et al.
  • Journal Title: Mol.Cancer Ther. 6(1) Pages: 269-276
• [Journal Article] Detachment-induced upregulation of XIAP and cIAP2 delays anoikis of intestinal epithelial cells. (2006)
  • Author(s): Liu Z et al.
  • Journal Title: Oncogene 25(59) Pages: 7680-7690
• [Journal Article] Activation of sterile20-like kinase 1 in proteasome inhibitor bortezomib-induced apoptosis in oncogenic K-ras-transformed cells. (2006)
  • Author(s): Teraishi F et al.
  • Journal Title: Cancer Res. 66(12) Pages: 6072-6079
• [Journal Article] KRAS(D13) Promotes apoptosis of human colorectal tumor cells by ReovirusT3D and oxaliplatin but not by tumor necrosis factor-related apoptosis-inducing ligand. (2006)
  • Author(s): Smakman N et al.
  • Journal Title: Cancer Res. 66(10) Pages: 5403-5408
• [Journal Article] Oncogenic Ras inhibits anoikis of intestinal epithelial cells by preventing the release of a mitochondrial pro-apoptotic protein Omi/HtrA2 into the cytoplasm. (2006)
  • Author(s): Liu Z et al.
  • Journal Title: J.Biol.Chem. 281(21) Pages: 14738-14747
• [Journal Article] Oncogenic Ras inhibits anoikis of intestinal epithelial cells by preventing the release of a mitochondrial pro-apoptotic protein Omi/HtrA2 into the cytoplasm. (2006)
  • Author(s): Liu Z et al.
  • Journal Title: J.Biol.Chem. (In press)
• [Journal Article] Role of epiregulin in peptidoglycan-induced proinflammatory cytokine production by antigen presenting cells (2005)
  • Author(s): Sugiyama S, Nakabayashi K, Baba I, Sasazuki T, Shlrasawa S.
  • Journal Title: Blochem. Biophys. Res. Commun. 337(1) Pages: 271-274
• [Journal Article] Multiple SNPs in intron 7 of thyrotropin receptor are associated with Graves' disease (2005)
  • Author(s): Hiratani H, Bowden DW, Ikegami S, Shirasawa S, Shimizu A, Iwatani Y, Akamizu T.
  • Journal Title: J. Clin. Endocrinol. Metab. 90(5) Pages: 2898-2903
• [Journal Article] A functional variant in FcRL3, encoding Fc Receptor-like 3, is associated with rheumatoid arthritis and several autoimmunities (2005)
  • Author(s): Kochi Y, Yamada R, Suzuki A, Harley JB, Shirasawa S, Sawada T, Bae S-C, Tokuhiro S, Chang X, Sekine A, Takahashi A, Tsunoda T, Ohnishi Y, Kaufman KM, Kang CP, Kang C, Otsubo S, Yumura W, Mimori A, Koike T, Nakamura Y, Sasazuki T, Yamamoto K.
  • Journal Title: Nature Genet. 37(5) Pages: 478-485
• [Journal Article] Lbx1 and Tlx3 are opposing switches in determining GABAergic versus glutamatergic transmitter phenotypes. (2005)
  • Author(s): Cheng L et al.
  • Journal Title: Nature Neurosci. 8(11) Pages: 1510-1515
• [Journal Article] Role of epiregulin in peptidoglycan-induced proinflammatory cytokine production by antigen presenting cells. (2005)
  • Author(s): Sugiyama S et al.
  • Journal Title: Biochem.Biophys.Res.Commun. 337(1) Pages: 271-274
• [Journal Article] Ischemia induced K-ras mutations in human colorectal cancer cells : role of microenvironmental regulation of MSH2 expression. (2005)
  • Author(s): Shahrzad S et al.
  • Journal Title: Cancer Res. 65 Pages: 8134-8141
• [Journal Article] Transformation by oncogenic Ras sensitizes human colon cells to TRAIL induced apoptosis by upregulating DR4 and DR5 through a MEK-dependent pathway. (2005)
  • Author(s): Drosopoulos KG et al.
  • Journal Title: J.Biol.Chem. 280(24) Pages: 22856-22867
• [Journal Article] Oncogenic Ras increases sensitivity of colon cancer cells to 5-FU-induced apoptosis. (2005)
  • Author(s): Klampfer L et al.
  • Journal Title: Oncogene 24(24) Pages: 3932-3941
• [Journal Article] Multiple SNPs in intron 7 of thyrotropin receptor are associated with Graves' disease. (2005)
  • Author(s): Hiratani H et al.
  • Journal Title: J.Clin.Endocrinol.Metab. 90(5) Pages: 2898-2903
• [Journal Article] A functional variant in FcRL3, encoding Fc Receptor-like 3, is associated with rheumatoid arthritis and several autoimmunities. (2005)
  • Author(s): Kochi Y et al.
  • Journal Title: Nature Genet. 37(5) Pages: 478-485
• [Presentation] Genome-wide survey of ZFAT-regulated genes in antigen-primed CD4+ T cell (2008)
  • Author(s): Yasuo Takashima, Midori Koyanagi, Keiko Doi, Iwai Baba, Yoko Tanaka, Toshiyuki Tsunoda, Takahiro Fujimoto, Kazuhiko Nakabayashi, Takehiko Sasazuki, Senji Shirasawa
  • Organizer: 第31回日本分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] 生命科学と創薬シーズの探索(招待口演-国内学会・研究会) (2008)
  • Author(s): 白澤専二
  • Organizer: 第40回日本臨床分子形態学会
  • Place of Presentation: 福岡
• [Presentation] BおよびT細胞におけるZFATの発現とその制御因子の解析 (2008)
  • Author(s): 角田俊之, 小柳緑, 藤本崇宏, 馬場賀, 中林一彦, 土井佳子, 高島康郎, 吉田康浩, 笹月健彦, 白澤専二
  • Organizer: 日本人類遺伝学会第52回大会
  • Place of Presentation: 東京
• [Presentation] Genome-wide survey of ZFAT-regulated genes in antigen-primed CD4^+ T cell. (2008)
  • Author(s): 高島康郎
  • Organizer: 第31回日本分子生物学会年会、第81回日本生化学会大会 合同大会
  • Place of Presentation: 神戸
• [Presentation] BおよびT細胞におけるZFATの発現とその制御因子の解析 (2008)
  • Author(s): 角田俊之
  • Organizer: 日本人類遺伝学会第53回大会
  • Place of Presentation: 横浜
• [Presentation] 免疫系転写関連因子ZFATの転写ネットワークの解明 (2007)
  • Author(s): 中林 一彦
  • Organizer: 日本人類遺伝学会第52回大会
  • Place of Presentation: 東京
  • Year and Date: 2007-09-14
• [Presentation] 免疫系転写関連因子ZFATの転写ネットワークの解明 (2007)
  • Author(s): 中林一彦, 藤本崇弘, 馬場賀, 小柳緑, 顧寧, 土井佳子, 加藤規弘, 笹月健彦, 白澤専二
  • Organizer: 日本人類遺伝学会第52回大会
• [Presentation] 新規免疫系転写因子 ZFAT・TR-ZFATを軸とする転写ネットワークとその生理機能の解明 (2006)
  • Author(s): 中林一彦、馬場賀、藤本崇弘、加藤規弘,笹月健彦、白澤専二
  • Organizer: 日本人類遺伝学会第51回大会
• [Presentation] Genome Analysis on Autoimmune Thyroid Disease(招待口演-国際学会・研究会) (2006)
  • Author(s): Shirasawa S.
  • Organizer: The 6^<th> HUGO-Pacific Meeting & the 7^<th> Asia-Pacific Conference on Human Genetics
  • Place of Presentation: Taipei
• [Presentation] 自己免疫性甲状腺疾患(AITD)感受性候補遺伝子ZFATの同定と機能解析 (2005)
  • Author(s): 中林一彦, 杉山滋, 馬場賀, 加藤規弘, 赤水尚志, 山本健, 笹月健彦, 白澤専二
  • Organizer: 第28回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] Epiregulin欠損マウスにおけるアトピー様皮膚炎発症の分子機構(招待口演-国内学会・研究会) (2005)
  • Author(s): 白澤専二
  • Organizer: 第55回日本アレルギー学会総会
  • Place of Presentation: 盛岡
• [Presentation] 自己免疫性甲状腺疾患のゲノム解析 (2005)
  • Author(s): 白澤専二, 石川繭子, 杉山滋, 中林一彦, 野本順子, 赤水尚史, 伴良行, 青木正幸, 山本健, 笹月健彦
  • Organizer: 日本人類遺伝学会第50回大会
  • Place of Presentation: 岡山
• [Book] 疾患ゲノム解析の現状と展望 「日本臨床」 Vol.67, No.3 : 469-476 (2009)
  • Author(s): 中林一彦, 田嶋敦, 白澤専二
• [Book] 自己免疫性甲状腺疾患感受性遺伝子の探索 「日本臨床」 Vol.64, No.12 : 2208-2214 (2006)
  • Author(s): 白澤専二
• [Book] 自己免疫性甲状腺疾患の疾患感受性遺伝子探査「ゲノム医科学NOW」 135-152 (2006)
  • Author(s): 白澤専二, 笹月健彦
• [Book] 自己免疫性甲状腺疾患感受性遺伝子の探索「蛋白質・核酸・酵素/増刊号 ゲノムから生命システムへ」 Vol.50 No.16, 2097-2102 (2005)
  • Author(s): 白澤専二, 笹月健彦
• [Book] ゲノムワイド研究と膠原病・自己免疫疾患 「リウマチ・膠原病最新トピックス -変わりゆく研究と診療」(竹原和彦, 佐藤伸一, 桑名正隆編, 診断と治療社) 6-9 (2005)
  • Author(s): 山田亮, 白澤専二
• [Book] 自己免疫性甲状腺疾患 「最新医学」 第60巻9月増刊号(「臨床遺伝子学'05-多因子遺伝病研究の最前線-」) 2087-2094 (2005)
  • Author(s): 白澤専二
• [Book] 自己免疫性甲状腺疾患感受性遺伝子とその探索 「ホルモンと臨床」 Vol.53, No.9, 11-16 (2005)
  • Author(s): 白澤専二
• [Book] 自己免疫性甲状腺疾患の疾患感受性遺伝子「Medical Practice」(M.P. 内科総合誌) : Vol.22 no.4, 633-635 (2005)
  • Author(s): 白澤専二
• [Remarks]
  • URL: http://www.med.fukuoka-u.ac.jp/cellbio/index-j.html
• [Remarks]
  • URL: http://www.med.fukuoka-u.ac.jp/cellbio/index-j.html
• [Patent(Industrial Property Rights)] ZFAT遺伝子発現抑制RNA (2008)
  • Inventor(s): 白澤専二、藤本崇宏、角田俊之、土井佳子、小柳緑
  • Industrial Property Rights Holder: 学校法人福岡大学
  • Filing Date: 2008-09-08