Research on the mechanism of epithelial cell differentiation and proliferation through novel keratin-binding proteins

2012 Fiscal Year Final Research Report

• Project/Area Number: 23770238
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cell biology
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: INOKO Akihito 愛知県がんセンター(研究所), 発がん制御研究部, 主任研究員 (30393127)
• Project Period (FY): 2011 – 2012
• Keywords: 上皮分化 / ケラチン / 中心体 / 細胞周期 / 一次線毛

Research Abstract

Keratin cytoskeleton is specifically observed in differentiated epithelial cells. Nevertheless, our knowledge of its contribution to epithelial cell differentiation and proliferation has been fragmentally. We identified keratin filament-binding proteins, Albatross and trichoplein, as TPHD (trichohyalin and plectin homology domain) proteins, according to their unique amino acid sequences. Indeed, growing evidences indicate that TPHD proteins are locationally and functionally "bi-player proteins" which coordinate differentiation and proliferation of epithelia. In this project, we published a report that trichoplein regulates cell proliferation through a novel mechanism, thus, centriolar trichoplein controls primary cilia kinetics that changes cell cycle progression and cellular quiescence. Also, this mechanism raised an idea how primary cilia-deficient cancer cells specifically damaged. Moreover, this finding of G1 phase regulation by primary cilia kinetics allowed us to examine its effect on cell differentiation in the future study.

Research Products

• [Journal Article] Cell cycle progression by the repression of primary cilia formation in proliferating cells. (2013)
  • Author(s): Goto H, Inoko A, Inagaki M.
  • Journal Title: Cell Mol Life Sci. Volume: (Epub ahead of print)
  • DOI: doi:10.1007/s00018-013-1302-8
  • Peer Reviewed
• [Journal Article] Trichoplein and Aurora A block aberrant primary cilia assembly in proliferating cells. (2012)
  • Author(s): Inoko A, Matsuyama M, Goto H, Ohmuro-Matsuyama Y, Hayashi Y, Enomoto M, Ibi M, Urano T, Yonemura S, Kiyono T, Izawa I, Inagaki M.
  • Journal Title: J Cell Biol. Volume: 197(3) Pages: 391-405
  • DOI: doi:10.1083/jcb.201106101
  • Peer Reviewed
• [Journal Article] Evidence that formation of vimentin mitogen-activated protein kinase (MAPK) complex mediates mast cell activation following FcεRI/CC chemokine receptor 1 cross-talk. (2012)
  • Author(s): Toda M, Kuo CH, Borman SK, Richardson RM, Inoko A, Inagaki M, Collins A, Schneider K, Ono SJ
  • Journal Title: J Biol Chem. Volume: 287(29) Pages: 24516-24
  • DOI: doi:10.1074/jbc.M111.319624
  • Peer Reviewed
• [Journal Article] Trichoplein controls microtubule anchoring at the centrosome by binding to Odf2 and ninein. (2011)
  • Author(s): Ibi M, Zou P, Inoko A, Shiromizu T, Matsuyama M, Hayashi Y, Enomoto M, Mori D, Hirotsune S, Kiyono T, Tsukita S, Goto H, Inagaki M.
  • Journal Title: J Cell Sci. Volume: 124 Pages: 857-864
  • Peer Reviewed
• [Journal Article] 一次線毛動態による新たな細胞増殖制御機構～トリコプレイン―オロラAキナーゼ経路～
  • Author(s): 猪子誠人, 稲垣昌樹
  • Journal Title: 化学と生物, 日本農芸化学学会誌 Volume: (in press)
  • Peer Reviewed
• [Presentation] Trichoplein and Aurora A block aberrant primary cilia assembly in proliferating cells (2012)
  • Author(s): Inoko et al.
  • Organizer: The 12th biennial Gordon Conference on Intermediate Filaments
  • Place of Presentation: Bates College (Lewiston, USA)
  • Year and Date: 20120617-22
• [Presentation] Trichoplein blocks aberrant assembly of primary cilia in proliferating cells (2011)
  • Author(s): Inoko A, Matsuyama M, Goto H, Ohmuro-Matsuyama Y, Inagaki M
  • Organizer: 67th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya
  • Year and Date: 2011-10-03
• [Remarks] Ben Short: News - In Focus: Trichoplein keeps primary cilia silent. J Cell Biol.;197(3): 341. 2012, doi:10.1083/jcb.1973if
  • URL: http://jcb.rupress.org/content/197/3/341.full
• [Remarks] F1000 Prime
  • URL: http://f1000.com/prime/714597892
• [Remarks] 愛知県がんセンター研究所のがん研究に関する新発見が 米科学誌で大きく紹介されました。
  • URL: http://www.pref.aichi.jp/cancer-center/ri/03event/press/120611.pdf
• [Remarks] ヒトのがん細胞だけを死滅させる特効薬の開発に大きなヒント-愛知がん研
  • URL: http://news.mynavi.jp/news/2012/06/12/087/index.html?gaibu=hon
• [Remarks] 科学誌ジャーナル・オブ・セル・バイオロジーで研究成果が大きく紹介されました。
  • URL: http://www.pref.aichi.jp/cancer-center/ri/01bumon/08hatsugan_seigyo/index.html
• [Remarks] 新着細胞生物学用語集(中間径フィラメント)
  • URL: http://www.jscb.gr.jp/glossary/category_glossary.php?category_id=4&category http://www.jscb.gr.jp/glossary/category_glossary.php?category_id=4&category