Investigation of cell function from the point of view of the regulatory mechanism for cellular localization of myocardin family members

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590332
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Osaka University
• Principal Investigator: HAYASHI Ken'ichiro 大阪大学, 医学(系)研究科(研究院), 准教授 (90238105)
• Co-Investigator(Renkei-kenkyūsha): NAKAGAWA Yoshiaki 京都大学, 農学研究科, 准教授 (80155689)
• Project Period (FY): 2011 – 2013
• Keywords: myocardin / MRTF-A/B / Crm1 / importin α/β1 / CCG-1423 / 核移行 / 核外移行 / 上皮間葉転換

Research Abstract

Myocardin (Mycd), a key factor for the smooth muscle cell differentiation, is constitutively located in the nucleus, whereas myocardin-related transcription factors A and B (MRTF-A/B), mostly reside in the cytoplasm and translocate to the nucleus in response to a signaling-induced decrease in G-actin. MRTF-A/B play a critical role in induction of epithelial-mesenchymal transition (EMT). Here, we investigated the regulatory mechanism for subcellular localization of Mycd family members and their related cell functions. Our studies revealed the following findings. 1) Regulatory mechanism of Crm1-mediated nuclear export of Mycd family members: critical differences in the regulation between Mycd and MRTF-A/B. 2) Inhibitory mechanism of CCG-1423 (a novel inhibitor of EMT) for the nuclear import of MRTF-A/B. 3) Activation of MRTF-A nuclear import by thymosin beta 4. 4) Novel function of Mycd RPEL motifs: actinrelated protein 5-mediated inhibition of Mycd function.

Research Products

• [Journal Article] RPEL proteins are the molecular targets for CCG-1423, an inhibitor of Rho signaling (2014)
  • Author(s): Hayashi, K., Watanabe, B., Nakagawa, Y., Minami, S., Morita, T.
  • Journal Title: PLOS ONE Volume: 9 Pages: e89016
  • DOI: 10.1371/journal.pone.0089016
• [Journal Article] G-actin sequestering protein thymosin-β4 regulates the activity of myocardin-related transcription factor
  • Author(s): Morita, T., Hayashi, K.
  • Journal Title: Biochemi Biophys. Res. Commun Volume: 437 Pages: 331-335
• [Journal Article] Importance of dimer formation of myocardin family members in the regulation of their nuclear export
  • Author(s): Hayashi, K., Morita, T.
  • Journal Title: Cell Struct. Funct Volume: 38 Pages: 123-134
• [Journal Article] Differences in the nuclear export mechanism between myocardin and myocardin-related transcription factors A
  • Author(s): Hayashi, K., Morita, T.
  • Journal Title: J. Biol. Chem Volume: 288 Pages: 5743-5755
• [Journal Article] Glucocorticoid suppresses dendritic spine development mediated by down-regulation of caldesmon expression
  • Author(s): Tanokashira, D., Morita, T., Hayashi, K., Mayanagi, T., Fukumoto, K., Kubota, Y., Yamashita, T., Sobue, K.
  • Journal Title: J. Neurosci Volume: 32 Pages: 14583-14591
• [Presentation] Myocardin-related transcription factor A and B (MRTF-A/B) are the molecular targets for CCG-1423, an inhibitor of Rho signaling (2014)
  • Author(s): 林謙一郎, 渡辺文太, 中川好秋, 南沙紀, 森田強
  • Organizer: 第66回日本細胞生物学会大会
  • Place of Presentation: 奈良県新公会堂
  • Year and Date: 2014-06-11
• [Presentation] Differences in the nuclear export mechanism between myocardin and MRTF-A (2012)
  • Author(s): 林謙一郎, 森田強
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡
  • Year and Date: 2012-12-16
• [Presentation] Inhibitory mechanism of Crm1-mediated nuclear export of myocardin (2012)
  • Author(s): 林謙一郎, 森田強
  • Organizer: 第45回日本細胞生物学会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2012-05-30