Elucidation of the mechanism of regulon switching controlled by Ad4BP

• Project/Area Number: 16K08593
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Kyushu University
• Principal Investigator: BABA Takashi 九州大学, 大学院医学研究院, 准教授 (40435524)
• Research Collaborator: Yokoyama Atsushi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 核内受容体 / 翻訳後修飾 / 代謝 / 遺伝子発現制御

Outline of Final Research Achievements

In this study, we identified three acetylation sites (K45, K392, and K435) of Ad4BP protein. Then, we tried to generate monoclonal antibodies recognizing each acetylated protein. We succeeded in generating anti-K392Ac-Ad4BP antibody, and are screening anti-K45Ac-Ad4BP and anti-K392Ac-Ad4BP antibodies. Spatio-temporal localization of acetylated Ad4BP in vivo will be determined by immunohistochemical staining with the antibodies. Moreover, we will perform ChIP-seq to identify genes regulated by acetylated Ad4BP to understand the mechanism of "regulon switching" in response to environmental stimuli.

Academic Significance and Societal Importance of the Research Achievements

本研究では副腎・生殖腺における糖濃度の変化に応答した代謝リプログラミング機構の解明を目指した。副腎・生殖腺はコレステロールから合成される多種のステロイドホルモンを産生・分泌することから、これらの組織における細胞内代謝系の破綻が、内分泌系を通 じて全身へ影響を及ぼす可能性は十分に考えられる。よって、外界刺激に応答したレギュロン制御メカニズムの理解は、恒常性の破綻によって引き起こされる疾患の根源的理解に向けて新たな視点を与える

Research Products

• [Journal Article] Mouse polycomb group gene Cbx2 promotes osteoblastic but suppresses adipogenic differentiation in postnatal long bones (2019)
  • Author(s): Katoh-Fukui Yuko、Baba Takashi、Sato Tetsuya、Otake Hiroyuki、Nagakui-Noguchi Yuko、Shindo Miyuki、Suyama Mikita、Ohkawa Yasuyuki、Tsumura Hideki、Morohashi Ken-ichirou、Fukami Maki
  • Journal Title: Bone Volume: 120 Pages: 219-231
  • DOI: 10.1016/j.bone.2018.10.021
  • Peer Reviewed / Open Access
• [Journal Article] Three population of adult Leydig cells in mouse testes revealed by a novel mouse HSD3BI-specific rat monoclonal antibody (2019)
  • Author(s): Chikako Yokoyama, Yuta Chigi, Takashi Baba, Atsushi Ohshitanai, Yumi Harada, Fumiya Tahahashi, Ken-ichirou Morohashi
  • Journal Title: BBRC Volume: 511 Issue: 4 Pages: 916-920
  • DOI: 10.1016/j.bbrc.2019.02.100
  • Peer Reviewed
• [Journal Article] Ad4BP/SF-1 regulates cholesterol synthesis to boost the production of steroids (2018)
  • Author(s): Takashi Baba, Hiroyuki Otake, Miki Inoue, Tetsuya Sato, Yasuhiro Ishihara, Ju-Yeon Moon, Megumi Tsuchiya, Kanako Miyabayashi, Hidesato Ogawa, Yuichi Shima, Lixiang Wang, Ryuichiro Sato, Takeshi Yamazaki, Mikita Suyama, Masatoshi Nomura, Man Ho Choi, Yasuyuki Ohkawa & Ken-ichirou Morohashi
  • Journal Title: Communications Biology Volume: 1 Issue: 1 Pages: 1-9
  • DOI: 10.1038/s42003-018-0020-z
  • NAID: 120006799378
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Alterations in Fetal Leydig Cell Gene Expression during Fetal and Adult Development. (2017)
  • Author(s): Miyabayashi K, Shima Y, Inoue M, Sato T, Baba T, Ohkawa Y, Suyama M, Morohashi KI.
  • Journal Title: Sex. Dev. Volume: 11 Pages: 53-63
  • Peer Reviewed
• [Journal Article] Identical NR5A1 Missense Mutations in Two Unrelated 46,XX Individuals with Testicular Tissues. (2017)
  • Author(s): Igarashi M, Fukami M et al.
  • Journal Title: Hum Mutat. Volume: 38 Issue: 1 Pages: 39-42
  • DOI: 10.1002/humu.23116
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Differential lactate and cholesterol synthetic activities in XY and XX Sertoli cells. (2017)
  • Author(s): Shishido Y, Baba T, Sato T, Shima Y, Miyabayashi K, Inoue M, Akiyama H, Kimura H, Kanal Y, Ishihara Y, Haraguchi S, Miyazaki A, Rozman D, Yamazaki T, Choi MH, Ohkawa Y, Suyama M, Morohashi KI
  • Journal Title: Sci Rep Volume: 7 Issue: 1 Pages: 41912-41912
  • DOI: 10.1038/srep41912
  • NAID: 120006799381
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of Ad4-binding protein/steroidogenic factor 1 in regulating NADPH production in adrenocortical Y-1 cells (2017)
  • Author(s): Li B, BabaT, Miyabayashi K, Sato T, Shima Y, Ichinose T, Miura D, Ohkawa Y, Suyama M, Morohashi KI
  • Journal Title: Endocrine Journal Volume: 64 Issue: 3 Pages: 315-324
  • DOI: 10.1507/endocrj.EJ16-0467
  • NAID: 130005529460
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access
• [Journal Article] Lysosomal activity maintains glycolysis and cyclin E1 expression by mediating Ad4BP/SF-1 stability for proper steroidogenic cell growth (2017)
  • Author(s): Syu JS, Baba T, Huang JY, Ogawa H, Hsieh CH, Hu JX, Chen TY, Lin TC, Tsuchiya M, Morohashi K, Huang BM, Lu FI
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 240-240
  • DOI: 10.1038/s41598-017-00393-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] ORCHESTRATION OF HOUSEKEEPING AND CELL-SPECIFIC METABOLISM FOR STEROID HORMONE SYNTHESIS BY A SINGLE TRANSCRIPTION FACTOR, Ad4BP/SF-1 (2018)
  • Author(s): Takashi Baba, Hiroyuki Otake, Miki Inoue, Kanako Miyabayashi, Yuichi Shima, Tetsuya Sato, Yasuyuki Ohkawa, Mikita Suyama, Ken-ichirou Morohashi.
  • Organizer: 8th International Symposium on Vertebrate Sex Determination
  • Int'l Joint Research
• [Presentation] Ad4BP/SF-1によるライディッヒ細胞の分化と代謝制御 (2017)
  • Author(s): 馬場崇
  • Organizer: 第4回発生における代謝を考える会
  • Place of Presentation: 京都大学 吉田キャンパス
  • Year and Date: 2017-02-21
• [Presentation] 核内受容体Ad4BP/SF-1によるステロイドホルモン産生の統括的制御 (2017)
  • Author(s): 馬場崇, 大竹博之, 井上実紀, 佐藤哲也, 石原康宏, 宮林香奈子, 嶋雄一, 山崎岳, 須山幹太, Choi Man-Ho, 大川恭行, 諸橋憲一郎
  • Organizer: 第21回日本生殖内分泌学会学術集会
  • Place of Presentation: 大阪 千里ライフサイエンスセンター
  • Year and Date: 2017-01-14
• [Presentation] Role of Ad4-Binding Protein/Steroidogenic Factor-1 (Ad4BP/SF-1) in regulating NADPH production in adrenocortical Y-1 cells (2017)
  • Author(s): Takashi Baba, Li Bing, Ken-ichirou Morohashi.
  • Organizer: Asian Sex Differentiation Network
  • Int'l Joint Research
• [Presentation] 核内受容体Ad4BP/SF-1による NADPH産生制御 (2017)
  • Author(s): 馬場 崇、Li Bing、諸橋 憲一郎
  • Organizer: 第25回日本ステロイドホルモン学会学術集会
• [Presentation] 核内受容体Ad4BP/SF-1によるステロイドホルモン産生へ向けた全プロセスの制御 (2017)
  • Author(s): 馬場 崇、諸橋 憲一郎
  • Organizer: ConBio2017
• [Presentation] 核内受容体Ad4BP/SF-1によるステロイドホルモン産生の全制御 (2016)
  • Author(s): 馬場崇, 大竹博之, 井上実紀, 石原泰宏, 宮林香奈子, 嶋雄一, 山崎岳, Man-Ho Choi, 諸橋憲一郎,
  • Organizer: 第24回日本ステロイドホルモン学会学術集会
  • Place of Presentation: 大分 ホルトホール大分
  • Year and Date: 2016-12-03
• [Presentation] 核内受容体Ad4BP/SF-1によるステロイドホルモン産生の全制御 (2016)
  • Author(s): 馬場崇, 大竹博之, 井上実紀, 佐藤哲也, 石原康宏, 宮林香奈子, 嶋雄一, 山崎岳, 須山幹太, Choi Man-Ho, 大川恭行, 諸橋憲一郎
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: 横浜 パシフィコ横浜
  • Year and Date: 2016-12-01
  • Invited
• [Presentation] 核内受容体Ad4BP/SF-1によるステロイドホルモン産生の全制御 (2016)
  • Author(s): 馬場崇
  • Organizer: 第1回次世代生命科学の研究会
  • Place of Presentation: 徳島大学
  • Year and Date: 2016-08-13
  • Invited
• [Presentation] 栄養・代謝と性 (2016)
  • Author(s): 馬場崇、井上実紀、諸橋憲一郎
  • Organizer: 第89回日本内分泌学会学術総会
  • Place of Presentation: 京都 京都国際会議場
  • Year and Date: 2016-04-21
  • Invited
• [Remarks]
• [Remarks]
• [Remarks] 所属研究室ホームページ
  • URL: http://www.med.kyushu-u.ac.jp/seisaseibutu/