Smad-mediated spliceosome assembly and alternative splicing

• Project/Area Number: 25670168
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Showa Pharmaceutical University
• Principal Investigator: SAKATA Nobuo 昭和薬科大学, 薬学部, 講師 (00170598)
• Co-Investigator(Kenkyū-buntansha): ITOH Susumu 昭和薬科大学, 薬学部, 教授 (70223154)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: Alternative splicing / Smad / LUC7L3 / JMJD6 / シグナル伝達研究の新展開 / スプライソソーム

Outline of Final Research Achievements

We examined the possibility that Smads, TGF-β signal transducer, are involved in the alternative splicing events producing splice variants. Among Smad binding proteins identified in proteomic analysis, we analyzed the interaction of LUC7L3, spliceosome components, and Smads by the co-immunoprecipitation (Co-IP) method in detail. Otherwise, the binding of these molecules was not identified. Therefore, we tested the interaction of JMJD6 and Smads, because JMJD6 are involved in alternative splicing and interacted with LUC7L3. JMJD6 was successfully interacted with Smad2 and Smad3 by the analysis of Co-IP. Further study is needed, which will be shed light on a new scheme of Smads and alternative splicing.

Research Products

• [Journal Article] TGF-β signaling cooperates with AT motif-binding factor-1 for repression of the α-fetoprotein promoter. (2014)
  • Author(s): Nobuo Sakata, Satoshi Kaneko, Souichi Ikeno, Yutaka Miura, Hidekazu Nakabayashi, Xue-Yuan Dong, Jin-Tang Dong, Taiki Tamaki, Naoko Nakano, Susumu Itoh
  • Journal Title: J. Signal Transduct. Volume: 2014 Pages: 970346-970346
  • DOI: 10.1155/2014/970346
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] C18ORF1: A Novel Negative Regulator of TGF-β Signaling. (2014)
  • Author(s): 2. Nakano N, Maeyama K, Ikeno S, Itoh F, Togawa Y, Katsu Y, Thanh Thao, VN, Watanabe Y, Kato M & Itoh, S.
  • Journal Title: J. Biol. Chem., Volume: 289 Issue: 18 Pages: 12680-12680
  • DOI: 10.1074/jbc.m114.558981
  • Peer Reviewed
• [Journal Article] ZFHX4 interacts with the NuRD core member CHD4 and regulates the glioblastoma tumor initiating cell state. (2013)
  • Author(s): Chudnovsky Y, Kim D, Zheng S, Whyte WA, Bansal M, Bray M, Gopal S, Theisen MA, Bilodeau S, Thiru P, Muffat J, Yilmaz OH, Mitalipova M, Woolard K, Lee J, Nishimura R, Sakata N, Fine HA, Carpenter AE, Silver SJ, Verhaak RGW, Califano A, Young RA, Ligon KL, Mellinghoff IK, Root DE, Sabatini DM, Hahn WC, Chheda MG
  • Journal Title: Cell Reports Volume: 6 Issue: 2 Pages: 1-12
  • DOI: 10.1016/j.celrep.2013.12.032
  • Peer Reviewed
• [Presentation] Transcriptional Repression Mechanisms of TGF-β Signaling and ATBF1 on the AFP Promoter (2015)
  • Author(s): Nobuo Sakata, Satoshi Kaneko, Souichi Ikeno, Yutaka Miura, Hidekazu Nakabayashi, Xue-Yuan Dong, Jin-Tang Dong, Taiki Tamaki, Naoko Nakano, Susumu Itoh
  • Organizer: Joint International Symposium on TGF-β Family and Cancer “Signal Network in Tumor Microenvironment”
  • Place of Presentation: つくば国際会議場（つくば市）
  • Year and Date: 2015-01-12 – 2015-01-13
• [Presentation] TMEPAIファミリーによるTGF-βシグナル制御機構 (2014)
  • Author(s): 中野なおこ、赤津俊介、中田美紀、伊東史子、坂田宣夫、葛祐紀、池野聡一、戸川陽子、伊東進
  • Organizer: 第58回日本薬学会関東支部会
  • Place of Presentation: 昭和薬科大学（町田市）
  • Year and Date: 2014-10-04
• [Presentation] 転写因子ATBF1とTGF-βシグナル伝達系によるalpha-fetoprotein遺伝子プロモーターの協調的抑制 (2014)
  • Author(s): 坂田宣夫、金子哲士、池野聡一、三浦裕、中林秀和、Xue-Yuan Dong、Jin-Tang Dong、玉置大器、中野なおこ、伊東進
  • Organizer: 第58回日本薬学会関東支部会
  • Place of Presentation: 昭和薬科大学（町田市）
  • Year and Date: 2014-10-04
• [Presentation] Negative regulation of α-fetoprotein gene transcription by TGF-β signaling with AT motif binding factor 1 (ATBF1) (2014)
  • Author(s): Nobuo Sakata, Satoshi Kaneko, Souichi Ikeno, Yutaka Miura, Hidekazu Nakabayashi, Xue-Yuan Dong, Jin-Tang Dong, Taiki Tamaki, Naoko Nakano, Susumu Itoh
  • Organizer: TGF-β Meeting in Leiden 2014 “TGF-β signal transduction in human disease”
  • Place of Presentation: Leiden Univ. Med. Center (Leiden, NL)
  • Year and Date: 2014-05-07 – 2014-05-10
• [Presentation] TGF-β Signaling Cooperates with AT Motif Binding Factor 1 (ATBF1) to Repress α-Fetoprotein Gene in Human Hepatoma Cells.
  • Author(s): Nobuo Sakata, Satoshi Kaneko, Souichi Ikeno, Yutaka Miura, Hidekazu Nakabayashi, Taiki Tamaki, Naoko Nakano, Susumu Itoh
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜（横浜市）
• [Presentation] 2.TGF-β signaling cooperate with ATBF1 in AFP transcription
  • Author(s): Nobuo Sakata, Satoshi Kaneko, Souichi Ikeno, Yutaka Miura, Hidekazu Nakabayashi, Xue-Yuan Dong, Jin-Tang Dong, Taiki Tamaki, Naoko Nakano, Susumu Itoh
  • Organizer: The 3rd International Symposium by JSPS Core-to-Core Program “Cooperative International Framework in TGF-β Family Signaling”
  • Place of Presentation: 大和屋本店（松山市）
• [Presentation] TGF-β/Smadシグナル伝達系と転写因子ATBF1によるα-fetoprotein遺伝子転写抑制
  • Author(s): 坂田宣夫、金子哲士、池野聡一、三浦裕、中林秀和、Xue-Yuan Dong、Jin-Tang Dong、玉置大器、中野なおこ、伊東進
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場（神戸市）