Analysis of the mechanism by which mutations of the FAM83H gene cause amelogenesis imperfecta

• Project/Area Number: 26460081
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: Kuga Takahisa 京都薬科大学, 薬学部, 助教 (20551857)
• Co-Investigator(Kenkyū-buntansha): 中山 祐治 京都薬科大学, 薬学部, 教授 (10280918) ; 朝長 毅 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 プロテオームリサーチプロジェクト, プロジェクトリーダー (80227644) ; 齊藤 洋平 京都薬科大学, 薬学部, 助教 (90411032) ; 佐々木 光穂 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 疾患モデル小動物研究室, プロジェクト研究員 (20432536)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: エナメル質形成不全症 / FAM83H / ケラチン / エナメル質 / 大腸がん / ケラチン骨格 / カゼインキナーゼ1 / 歯 / カゼインキナーゼI / デスモソーム

Outline of Final Research Achievements

FAM83H plays an essential role in the formation of dental enamel and its heterozygous mutation causes autosomal-dominant hypocalcified amelogenesis imperfecta. We have demonstrated that FAM83H regulates the organization of the keratin cytoskeleton in human colorectal cancer cells. In the present study, we showed that the keratin cytoskeleton in cultured ameloblastoma cells is also regulated by FAM83H. Mutant proteins of FAM83H prevented proper organization of the keratin cytoskeleton and concomitantly dis-localized component proteins of desmosomes form the cell-cell interface in cultured ameloblastoma cells. We additionally generated mice with a mutation in the FAM83H gene. We are testing whether the FAM83H mutation causes the disorganization of the keratin cytoskeleton and desmosomes in dental ameloblasts in vivo.

Research Products

• [Journal Article] Requirement of Hsp105 in CoCl2-induced HIF-1α accumulation and transcriptional activation (2017)
  • Author(s): Mikami H, Saito Y, Okamoto N, Kakihana A, Kuga T, Nakayama Y
  • Journal Title: Experimental Cell Research Volume: 352 Issue: 2 Pages: 225-233
  • DOI: 10.1016/j.yexcr.2017.02.004
  • Peer Reviewed
• [Journal Article] Src acts as an effector for Ku70-dependent suppression of apoptosis through phosphorylation of Ku70 at Tyr-530 (2017)
  • Author(s): Morii, M., Kubota, S., Honda, T., Yuki, R., Morinaga, T., Kuga, T., Tomonaga, T., Yamaguchi, N.-t., and Yamaguchi, N.
  • Journal Title: Journal of Biological Chemistry Volume: 292 Issue: 5 Pages: 1648-1665
  • DOI: 10.1074/jbc.m116.753202
  • Peer Reviewed
• [Journal Article] Tyrosine Phosphorylation of the Pioneer Transcription Factor FoxA1 Promotes Activation of Estrogen Signaling. (2017)
  • Author(s): Noritaka Yamaguchi, Misato Shibazaki, Chiaki Yamada, Erina Anzai, Mariko Morii, Yuji Nakayama, Takahisa Kuga, Yuuki Hashimoto, Takeshi Tomonaga, and Naoto Yamaguchi.
  • Journal Title: Journal of Cellular Biochemistry Volume: 118 Issue: 6 Pages: 1453-1461
  • DOI: 10.1002/jcb.25804
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] v-Src-induced nuclear localization of YAP is involved in multipolar spindle formation in tetraploid cells (2017)
  • Author(s): Kakae K, Ikeuchi M, Kuga T, Saito Y, Yamaguchi N, Nakayama Y
  • Journal Title: Cell Signalling Volume: 30 Pages: 19-29
  • DOI: 10.1016/j.cellsig.2016.11.014
  • Peer Reviewed
• [Journal Article] FAM83H and casein kinase I regulate the organization of the keratin cytoskeleton and formation of desmosomes (2016)
  • Author(s): Kuga T, Sasaki M, Mikami T, Miake Y, Adachi J, Shimizu M, Saito Y, Koura M, Takeda Y, Matsuda J, Tomonaga T, Nakayama Y
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 26557-26557
  • DOI: 10.1038/srep26557
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Casein kinase 1 is recruited to nuclear speckles by FAM83H and SON (2016)
  • Author(s): Kuga T, Kume H, Adachi J, Kawasaki N, Shimizu M, Hoshino I, Matsubara H, Saito Y, Nakayama Y, Tomonaga T
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 34472-34472
  • DOI: 10.1038/srep34472
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Expression of Wilms’ tumor 1 (WT1) in ameloblastomas (2016)
  • Author(s): Bologna-Molina R, Takeda Y, Kuga T, Chosa N, Kitagawa M, Takata T, Ishisaki A, Mikami T
  • Journal Title: Journal of Oral Science Volume: 58 Issue: 3 Pages: 407-413
  • DOI: 10.2334/josnusd.15-0546
  • NAID: 130005266252
  • ISSN: 1343-4934, 1880-4926
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fibrinogen alpha C chain 5.9 kDa fragment (FIC5.9), a biomarker for various pathological conditions, is produced in post-blood collection by fibrinolysis and coagulation factors (2016)
  • Author(s): Kikuchi W, Nishimura M, Kuga T, Tsuchida S, Saito T, Satoh M, Noda K, Kodera Y, Tomonaga T, Nomura F
  • Journal Title: Clinical Proteomics Volume: 13 Issue: 1 Pages: 27-27
  • DOI: 10.1186/s12014-016-9129-6
  • Peer Reviewed / Open Access
• [Journal Article] v-Src Causes Chromosome Bridges in a Caffeine-Sensitive Manner by Generating DNA Damage (2016)
  • Author(s): Masayoshi Ikeuchi, Yasunori Fukumoto, Takuya Honda, Takahisa Kuga, Youhei Saito, Naoto Yamaguchi and Yuji Nakayama
  • Journal Title: International Journal of Molecular Sciences Volume: 17(6) Issue: 6 Pages: 871-871
  • DOI: 10.3390/ijms17060871
  • Peer Reviewed / Open Access
• [Journal Article] Yeast two-hybrid and one-hybrid screenings identify regulators of hsp70 gene expression (2016)
  • Author(s): Saito Y, Nakagawa T, Kakihana A, Nakamura Y, Nabika T, Kasai M, Takamori M, Yamagishi N, Kuga T, Hatayama T, Nakayama Y.
  • Journal Title: Journal of Cellular Biochemistry. Volume: in press Issue: 9 Pages: 2109-2117
  • DOI: 10.1002/jcb.25517
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] ERK plays a role in chromosome alignment and participates in M-phase progression. (2016)
  • Author(s): Iwamoto E, Ueta N, Matsui Y, Kamijo K, Kuga T, Saito Y, Yamaguchi N, Nakayama Y.
  • Journal Title: J. Cell. Biochem. Volume: 117 Issue: 6 Pages: 1340-1351
  • DOI: 10.1002/jcb.25424
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] c-Abl-mediated tyrosine phosphorylation of JunB is required for Adriamycin-induced expression of p21. (2015)
  • Author(s): Noritaka Yamaguchi, Ryuzaburo Yuki, Sho Kubota, Kazumasa Aoyama, Takahisa Kuga, Yuuki Hashimoto, Takeshi Tomonaga, and Naoto Yamaguchi.
  • Journal Title: Biochemical Journal Volume: 471 Issue: 1 Pages: 67-77
  • DOI: 10.1042/bj20150372
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] c-Abl induces stabilization of histone deacetylase 1 (HDAC1) in a kinase activity-dependent manner. (2015)
  • Author(s): Kazumasa Aoyama, Noritaka Yamaguchi, Ryuzaboro Yuki, Mariko Morii, Sho Kubota, Kensuke Hirata, Kohei Abe, Takuya Honda, Takahisa Kuga, Yuuki Hashimoto, Takeshi Tomonaga, and Naoto Yamaguchi
  • Journal Title: Cell Biology International Volume: 39 Issue: 4 Pages: 446-456
  • DOI: 10.1002/cbin.10413
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Role for Tyrosine Phosphorylation of A-kinase Anchoring Protein 8 (AKAP8) in its Dissociation from Chromatin and the Nuclear Matrix (2015)
  • Author(s): Kubota S, Morii M, Yuki R, Yamaguchi N, Yamaguchi H, Aoyama K, Kuga T, Tomonaga T, Yamaguchi N.
  • Journal Title: J Biol Chem Volume: 290 Issue: 17 Pages: 10891-904
  • DOI: 10.1074/jbc.m115.643882
  • Peer Reviewed / Open Access
• [Journal Article] Nuclear accumulation of annexin A2 contributes to chromosomal instability by coilin-mediated centromere damage (2015)
  • Author(s): Kazami, T., Nie, H., Satoh, M., Kuga, T., Matsushita, K., Kawasaki, N., Tomonaga, T*., and Nomura, F
  • Journal Title: Oncogene Volume: in press Issue: 32 Pages: 4177-4189
  • DOI: 10.1038/onc.2014.345
  • Peer Reviewed
• [Journal Article] Discovery of colorectal cancer biomarker candidates by membrane proteomic analysisand subsequent verification using selected reaction monitoring and tissue microarrayanalysis (2014)
  • Author(s): Kume H, Muraoka S, Kuga T, Adachi J, Narumi R, Watanabe S, Kuwano M, Kodera Y, Matsushita K, Fukuoka J, Masuda T, Ishihama Y, Matsubara H, Nomura F, Tomonaga T.
  • Journal Title: Mol Cell Proteomics. Volume: M113 Issue: 6 Pages: 37093-37093
  • DOI: 10.1074/mcp.m113.037093
  • Peer Reviewed
• [Journal Article] Nmi interacts with Hsp105beta and enhances the Hsp105beta-mediated Hsp70 expression (2014)
  • Author(s): Saito Y, Yukawa A, Matozaki M, Mikami H, Yamagami T, Kuga T, Yamagishi N, Hatayama T, Nakayama Y
  • Journal Title: Experimental Cell Research Volume: 327 Issue: 1 Pages: 163-170
  • DOI: 10.1016/j.yexcr.2014.07.023
  • Peer Reviewed
• [Journal Article] Genistein induces cytokinesis failure through RhoA delocalization and anaphase chromosome bridging. (2014)
  • Author(s): Nakayama Y, Saito Y, Soeda S, Iwamoto E, Ogawa S, Yamagishi N, Kuga T, Yamaguchi N
  • Journal Title: J Cell Biochem. Volume: 115 Issue: 4 Pages: 763-771
  • DOI: 10.1002/jcb.24720
  • Peer Reviewed
• [Journal Article] Increased expression of sorcin is associated with multidrug resistance in leukemia cells via up-regulation of MDR1 expression through cAMP response element-binding protein (2014)
  • Author(s): Yamagishi N, Nakaoka R, Kondo R, Nishituji M, Saito Y, Kuga T, Hatayama T, Nakayama Y
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 448 Issue: 4 Pages: 430-436
  • DOI: 10.1016/j.bbrc.2014.04.125
  • Peer Reviewed
• [Journal Article] Lamin B2 prevents chromosome instability by ensuring proper mitotic chromosome segregation (2013)
  • Author(s): Kuga, T., Nie, H., Kazami, T., Satoh, M., Matsushita, K., Nomura, F., Maeshima, K., Nakayama, Y., Tomonaga, T.
  • Journal Title: Oncogenesis Volume: 3 Issue: 3 Pages: e94-e94
  • DOI: 10.1038/oncsis.2014.6
  • Peer Reviewed
• [Presentation] FAM83Hは新規のがん浸潤関連タンパク質である (2017)
  • Author(s): 久家貴寿、齊藤洋平、朝長毅、中山祐治
  • Organizer: 日本薬学会 第137年会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-24
• [Presentation] インタラクトーム解析を用いた疾患関連タンパク質FAM83Hの解析 (2015)
  • Author(s): 久家貴寿、朝長毅、中山祐治
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-25 – 2015-03-28
  • Invited
• [Presentation] FAM83H regulates organization of the keratin cytoskeleton in colorectal cancer cells (2014)
  • Author(s): Kuga T, Saito, Y, Yamagishi N, Tomonaga T, Nakayama Y
  • Organizer: The 2014 ASCB meeting
  • Place of Presentation: Phirladelphia
  • Year and Date: 2014-12-06 – 2014-12-10