2021/12/04 更新

写真a

カキハラ ヨシト
柿原 嘉人
KAKIHARA Yoshito
所属
教育研究院 医歯学系 歯学系列 助教
医歯学総合研究科 口腔生命科学専攻 顎顔面再建学 助教
職名
助教
外部リンク

学位

  • 博士(医学) ( 2003年5月   大阪大学 )

研究キーワード

  • 骨代謝

  • 分子シャペロン

  • Hsp90

  • R2TP complex

  • 口腔癌

研究分野

  • ライフサイエンス / 薬理学

経歴

  • 新潟大学   医歯学総合研究科 口腔生命科学専攻 顎顔面再建学   助教

    2014年7月 - 現在

留学歴

  • トロント大学医学部生化学講座   博士研究員

    2005年6月 - 2014年6月

 

論文

  • Effects of rice fermented extracts, "Sake Lees", on the functional activity of odontoblast-like cells (KN-3 cells).

    Keiichiro Okamoto, Yoshito Kakihara, Naoto Ohkura, Aiko Tohma, Ayako Washio, Chiaki Kitamura, Yuichiro Noiri, Kensuke Yamamura, Makio Saeki

    Odontology   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    This study was designed to investigate the effects of Sake Lees extracts (SLE, Sake Kasu) on the functional activity of odontoblastic cells and tooth pulp of the rats. For in vitro studies, a rat clonal odontoblast-like cell line, KN-3 cells were cultured. SLE significantly decreased KN-3 cell proliferation, but showed no significant cytotoxicity. SLE effects on several protein productions of KN-3 cells were compared with PBS. SLE and PBS increased alkaline phosphatase (ALP), dentin sialoprotein (DSP), and osterix in a day-course dependent manner, while SLE increased the induction of ALP on day 9-21 and DSP on day 15-21. SLE also increased Runx2 expression on day 3 and 9 compared to PBS. Alizarin Red stainings revealed that SLE showed a subtle increase in mineralization of KN-3 cells on day 15 and 21. A histological investigation was conducted to assess if SLE induced reparative dentin formation after direct capping at the exposed tooth pulp in rats, suggesting that SLE could increase the reparative dentin formation more than PBS. These findings suggest that Sake Lees could have functional roles in the alterations of odontoblastic activity, which might influence the physiology of the tooth pulp.

    DOI: 10.1007/s10266-021-00654-9

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  • HEATR1, a novel interactor of Pontin/Reptin, stabilizes Pontin/Reptin and promotes cell proliferation of oral squamous cell carcinoma

    Akihiko Nakamura, Yoshito Kakihara, Akinori Funayama, Kenta Haga, Toshihiko Mikami, Daiki Kobayashi, Yutaka Yoshida, Kenji Izumi, Tadaharu Kobayashi, Makio Saeki

    Biochemical and Biophysical Research Communications   557   294 - 301   2021年6月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.bbrc.2021.04.021

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  • Identification and characterization of R2TP in the development of oral squamous cell carcinoma

    Tetsuo Kiguchi, Yoshito Kakihara, Manabu Yamazaki, Kouji Katsura, Kenji Izumi, Jun-ichi Tanuma, Takashi Saku, Ritsuo Takagi, Makio Saeki

    Biochemical and Biophysical Research Communications   548   161 - 166   2021年4月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.bbrc.2021.02.074

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  • Reptinは胎仔上皮におけるDNA損傷応答を介して器官形成を制御する

    目黒 史也, 柿原 嘉人, 川崎 真依子, 川崎 勝盛, 丹原 惇, トゥラカナン・スッパラック, 工藤 武久, 山田 茜, 前田 健康, 多部田 康一, 佐伯 万騎男, 大峡 淳

    新潟歯学会雑誌   50 ( 2 )   115 - 116   2020年12月

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    記述言語:日本語   出版者・発行元:新潟歯学会  

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  • Construction of an artificial system for ambrein biosynthesis and investigation of some biological activities of ambrein. 国際誌

    Yota Yamabe, Yukina Kawagoe, Kotone Okuno, Mao Inoue, Kanako Chikaoka, Daijiro Ueda, Yuko Tajima, Tadasu K Yamada, Yoshito Kakihara, Takashi Hara, Tsutomu Sato

    Scientific reports   10 ( 1 )   19643 - 19643   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Ambergris, a sperm whale metabolite, has long been used as a fragrance and traditional medication, but it is now rarely available. The odor components of ambergris result from the photooxidative degradation of the major component, ambrein. The pharmacological activities of ambergris have also been attributed to ambrein. However, efficient production of ambrein and odor compounds has not been achieved. Here, we constructed a system for the synthesis of ambrein and odor components. First, we created a new triterpene synthase, "ambrein synthase," for mass production of ambrein by redesigning a bacterial enzyme. The ambrein yields were approximately 20 times greater than those reported previously. Next, an efficient photooxidative conversion system from ambrein to a range of volatiles of ambergris was established. The yield of volatiles was 8-15%. Finally, two biological activities, promotion of osteoclast differentiation and prevention of amyloid β-induced apoptosis, were discovered using the synthesized ambrein.

    DOI: 10.1038/s41598-020-76624-y

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  • リボソーム合成関連因子HEATR1は、Pontin/Reptin complexと共に口腔扁平上皮癌進展に寄与する

    中村 彬彦, 木口 哲郎, 高木 律男, 船山 昭典, 小林 正治, 柿原 嘉人, 佐伯 万騎男

    日本口腔科学会雑誌   69 ( 2 )   132 - 132   2020年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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  • ROCK inhibitors enhance bone healing by promoting osteoclastic and osteoblastic differentiation. 査読 国際誌

    Juri Nakata, Yosuke Akiba, Jun Nihara, Lay Thant, Kaori Eguchi, Hiroko Kato, Kenji Izumi, Mariko Ohkura, Masanori Otake, Yoshito Kakihara, Isao Saito, Makio Saeki

    Biochemical and biophysical research communications   526 ( 3 )   547 - 552   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Osteoclast and osteoblast are essential for proper bone development and remodeling as well as recovery of bone fracture. In this study, we seek chemical compounds that enhance turnover of bone metabolism for promoting bone healing. First, we screen a chemical library which includes 378 compounds by using murine pre-osteoclastic RAW264.7 cells to identify compounds that promote osteoclastic differentiation. We find that two ROCK (Rho-associated coiled-coil kinase) inhibitors, HA-1077 (Fasudil) and Y-27632, enhance osteoclastogenesis. Subsequently, we identify that these two compounds also increase osteoblastic differentiation of MC3T3-E1 cells. Finally, our in vivo experiment shows that the local administration of ROCK inhibitors accelerate the bone healing of the rat calvarial defect.

    DOI: 10.1016/j.bbrc.2020.03.033

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  • Daily administration of Sake Lees (Sake Kasu) reduced psychophysical stress-induced hyperalgesia and Fos responses in the lumbar spinal dorsal horn evoked by noxious stimulation to the hindpaw in the rats. 査読

    Shimizu S, Nakatani Y, Kakihara Y, Taiyoji M, Saeki M, Takagi R, Yamamura K, Okamoto K

    Bioscience, biotechnology, and biochemistry   84 ( 1 )   159 - 170   2020年1月

  • R2TP/PAQosome as a promising chemotherapeutic target in cancer 招待 査読

    Kakihara Y, Kiguchi T, Ohazama A, Saeki M

    Japanese Dental Science Review   56 ( 1 )   38 - 42   2019年12月

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  • Structures of the cGMP-dependent protein kinase in malaria parasites reveal a unique structural relay mechanism for activation. 査読

    El Bakkouri M, Kouidmi I, Wernimont AK, Amani M, Hutchinson A, Loppnau P, Kim JJ, Flueck C, Walker JR, Seitova A, Senisterra G, Kakihara Y, Kim C, Blackman MJ, Calmettes C, Baker DA, Hui R

    Proceedings of the National Academy of Sciences of the United States of America   116 ( 28 )   14164 - 14173   2019年7月

  • Bmp signaling in molar cusp formation. 査読 国際誌

    Fumiya Meguro, Thantrira Porntaveetus, Maiko Kawasaki, Katsushige Kawasaki, Akane Yamada, Yoshito Kakihara, Makio Saeki, Koichi Tabeta, John A Kessler, Takeyasu Maeda, Atsushi Ohazama

    Gene expression patterns : GEP   32   67 - 71   2019年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Tooth cusp is a crucial structure, since the shape of the molar tooth is determined by number, shape, and size of the cusp. Bone morphogenetic protein (Bmp) signaling is known to play a critical role in tooth development, including in initiation. However, it remains unclear whether Bmp signaling is also involved in cusp formation. To address this question, we examined cusp in two different transgenic mouse lines: mice with overexpression of Bmp4 (K14-Bmp4), and those with Bmp inhibitor, Noggin, (K14-Noggin) under keratin14 (K14) promoter. K14-Noggin mice demonstrated extra cusps, whereas reduced number of cusps was observed in K14-Bmp4 mice. To further understand how Bmps are expressed during cusp formation, we performed whole-mount in situ hybridisation analysis of three major Bmps (Bmp2, Bmp4, and Bmp7) in murine maxillary and mandibular molars from E14.5 to P3. The linear expressions of Bmp2 and Bmp4 were observed in both maxillary and mandibular molars at E14.5. The expression patterns of Bmp2 and Bmp4 became significantly different between the maxillary and mandibular molars at E16.5. At P3, all Bmps were expressed in all the cusp regions of the maxillary molar; however, the patterns differed. All Bmps thus exhibited dynamic temporo-spatial expression during the cusp formation. It could therefore be inferred that Bmp signaling is involved in regulating cusp formation.

    DOI: 10.1016/j.gep.2019.04.002

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  • Fusaspirols A-D, novel oxaspirol derivatives isolated from Fusarium solani B-18 査読

    Ariefta Nanang Rudianto, Nikmawahda, Hasna Tazkia, Aboshi Takako, Murayama Tetsuya, Tawaraya Keitaro, Koseki Takuya, Katagi Genta, Kakihara Yoshito, Shiono Yoshihito

    TETRAHEDRON   75 ( 10 )   1371 - 1377   2019年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.tet.2019.01.052

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  • Japanese Rice Wine can reduce psychophysical stress-induced depression-like behaviors and Fos expression in the trigeminal subnucleus caudalis evoked by masseter muscle injury in the rats. 査読

    Nakatani Y, Kakihara Y, Shimizu S, Kurose M, Sato T, Kaneoke M, Saeki M, Takagi R, Yamamura K, Okamoto K

    Bioscience, biotechnology, and biochemistry   1 - 11   2018年10月

  • Systems analysis of the genetic interaction network of yeast molecular chaperones 査読

    Rizzolo Kamran, Kumar Ashwani, Kakihara Yoshito, Phanse Sadhna, Minic Zoran, Snider Jamie, Stagljar Igor, Zilles Sandra, Babu Mohan, Houry Walid A

    MOLECULAR OMICS   14 ( 2 )   82 - 94   2018年4月

  • The effect of ROCK inhibitor on bone remodeling 査読

    Juri Nakata, Yosuke Akiba, Kaori Eguchi, Jun Nihara, Isao Saito, Yoshito Kakihara, Makio Saeki

    JOURNAL OF BONE AND MINERAL RESEARCH   32   S229 - S229   2017年12月

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    記述言語:英語   出版者・発行元:WILEY  

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  • Features of the Chaperone Cellular Network Revealed through Systematic Interaction Mapping 査読

    Kamran Rizzolo, Jennifer Huen, Ashwani Kumar, Sadhna Phanse, James Vlasblom, Yoshito Kakihara, Hussein A. Zeineddine, Zoran Minic, Jamie Snider, Wen Wang, Carles Pons, Thiago V. Seraphim, Edgar Erik Boczek, Simon Alberti, Michael Costanzo, Chad L. Myers, Igor Stagljar, Charles Boone, Mohan Babu, Walid A. Houry

    CELL REPORTS   20 ( 11 )   2735 - 2748   2017年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CELL PRESS  

    A comprehensive view of molecular chaperone function in the cell was obtained through a systematic global integrative network approach based on physical (protein-protein) and genetic (gene-gene or epistatic) interaction mapping. This allowed us to decipher interactions involving all core chaperones (67) and cochaperones (15) of Saccharomyces cerevisiae. Our analysis revealed the presence of a large chaperone functional supercomplex, which we named the naturally joined (NAJ) chaperone complex, encompassing Hsp40, Hsp70, Hsp90, AAA+, CCT, and small Hsps. We further found that many chaperones interact with proteins that form foci or condensates under stress conditions. Using an in vitro reconstitution approach, we demonstrate condensate formation for the highly conserved AAA+ ATPases Rvb1 and Rvb2, which are part of the R2TP complex that interacts with Hsp90. This expanded view of the chaperone network in the cell clearly demonstrates the distinction between chaperones having broad versus narrow substrate specificities in protein homeostasis.

    DOI: 10.1016/j.celrep.2017.08.074

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  • GSK-3 beta inhibitory activities of novel dichroloresorcinol derivatives from Cosmospora vilior isolated from a mangrove plant 査読

    Yoshihito Shiono, Nozomi Miyazaki, Tetsuya Murayama, Takuya Koseki, Harizon, Dewa Gede Katja, Unang Supratman, Juri Nakata, Yoshito Kakihara, Makio Saeki, Jun Yoshida, Shota Uesugi, Ken-ichi Kimura

    PHYTOCHEMISTRY LETTERS   18   122 - 127   2016年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Cosmochlorins A (1), B (2), and C (3) were isolated from the endophytic fungus Cosmospora vilior IM2-155. The structures of 1, 2, and 3 were elucidated by a combination of extensive spectroscopic analyses, including extensive 2D NMR, HRESITOFMS, and chemical reactions. Compounds 1, 2, and 3 were evaluated for their biological activity. Compounds 1 and 2 partially restored the growth inhibition caused by hyperactivated Ca2+-signaling in mutant yeast and showed glycogen synthase kinase (GSK)-3b inhibition activity at IC50 values of 62.5 and 60.6 mu M, respectively. Further, compound 2 significantly increased osteoclast formation by more than 1.5-fold in RAW264.7 cells compared to receptor activator of nuclear factor-kB ligand (RANKL) alone. (C) 2016 Phytochemical Society of Europe. Published by Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.phytol.2016.09.007

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  • The inhibitors of cyclin-dependent kinases and GSK-3β enhance osteoclastogenesis. 査読

    Akiba Y, Mizuta A, Kakihara Y, Nakata J, Nihara J, Saito I, Egusa H, Saeki M

    Biochemistry and biophysics reports   5   253 - 258   2016年3月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.bbrep.2015.12.011

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  • Discovering novel drugs for modulating osteoclastogenesis 査読

    Kakihara Yoshito, Nakata Juni, Kiyokawa Yuki, Yamashita Naoyuki, Shiono Yoshihito, Saeki Makio

    JOURNAL OF PHARMACOLOGICAL SCIENCES   130 ( 3 )   S208   2016年3月

  • The effect of CDK inhibitors on osteoclast differentiation 査読

    Yoshito Kakihara, Juri Nakata, Yosuke Akiba, Hiroshi Egusa, Makio Saeki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   128 ( 3 )   S242 - S242   2015年7月

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    記述言語:英語   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • The R2TP chaperone complex: Its involvement in snoRNP assembly and tumorigenesis 査読

    Yoshito Kakihara, Makio Saeki

    Biomolecular Concepts   5 ( 6 )   513 - 520   2014年12月

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    記述言語:英語   出版者・発行元:De Gruyter Mouton  

    R2TP was originally identified in yeast Saccharomyces cerevisiae as Hsp90 interacting complex, and is composed of four different proteins: Rvb1, Rvb2, Tah1, and Pih1. This complex is well-conserved in eukaryotes, and is involved in many cellular processes such as snoRNP biogenesis, RNA polymerase assembly, PIKK signaling, and apoptosis. An increasing number of research related to R2TP suggests a linkage of its function with tumorigenesis. In this review, we provide an overview of several recent studies on R2TP that are related to cell proliferation and carcinogenesis, and propose a possible role of R2TP in tumorigenesis through regulating snoRNA/snoRNP biogenesis.

    DOI: 10.1515/bmc-2014-0028

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  • Nutritional status modulates box C/D snoRNP biogenesis by regulated subcellular relocalization of the R2TP complex. 査読

    Kakihara Y, Makhnevych T, Zhao L, Tang W, Houry WA

    Genome biology   15 ( 7 )   404   2014年7月

  • Nutritional status modulates box C/D snoRNP biogenesis by regulated subcellular relocalization of the R2TP complex 査読

    Yoshito Kakihara, Taras Makhnevych, Liang Zhao, Weiwen Tang, Walid A. Houry

    GENOME BIOLOGY   15 ( 7 )   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: Box C/D snoRNPs, which are typically composed of box C/D snoRNA and the four core protein components Nop1, Nop56, Nop58, and Snu13, play an essential role in the modification and processing of pre-ribosomal RNA. The highly conserved R2TP complex, comprising the proteins Rvb1, Rvb2, Tah1, and Pih1, has been shown to be required for box C/D snoRNP biogenesis and assembly; however, the molecular basis of R2TP chaperone-like activity is not yet known.
    Results: Here, we describe an unexpected finding in which the activity of the R2TP complex is required for Nop58 protein stability and is controlled by the dynamic subcellular redistribution of the complex in response to growth conditions and nutrient availability. In growing cells, the complex localizes to the nucleus and interacts with box C/D snoRNPs. This interaction is significantly reduced in poorly growing cells as R2TP predominantly relocalizes to the cytoplasm. The R2TP-snoRNP interaction is mainly mediated by Pih1.
    Conclusions: The R2TP complex exerts a novel regulation on box C/D snoRNP biogenesis that affects their assembly and consequently pre-rRNA maturation in response to different growth conditions.

    DOI: 10.1186/s13059-014-0404-4

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  • PIH1D1 interacts with mTOR complex 1 and enhances ribosome RNA transcription 査読

    Yuya Kamano, Makio Saeki, Hiroshi Egusa, Yoshito Kakihara, Walid A. Houry, Hirofumi Yatani, Yoshinori Kamisaki

    FEBS Letters   587 ( 20 )   3303 - 3308   2013年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PIH1D1 is the defining component of the R2TP complex. Recently, R2TP has been reported to stabilize mTOR (mammalian target of rapamycin), an important regulator of cell growth and protein synthesis. Two complexes of mTOR, mTORC1 and mTORC2, have been identified. We demonstrate that immunoprecipitation (IP) of PIH1D1 results in the co-IP of Raptor (mTORC1 specific), but not Rictor (mTORC2 specific), and that knockdown of PIH1D1 decreases mTORC1 assembly, S6 kinase phosphorylation (indicator of mTORC1 activity), and rRNA transcription without affecting mTORC2 in human breast cancer MCF-7 cells. In addition, we provide evidence that PIH1D1 is overexpressed in various breast cancer cell lines. These findings collectively suggest that PIH1D1 may have an important role in mTORC1 regulation in breast cancers. © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.febslet.2013.09.001

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  • Exosome-Bound WD Repeat Protein Monad Inhibits Breast Cancer Cell Invasion by Degrading Amphiregulin mRNA 査読

    Makio Saeki, Hiroshi Egusa, Yuya Kamano, Yoshito Kakihara, Walid A. Houry, Hirofumi Yatani, Shinzaburo Noguchi, Yoshinori Kamisaki

    PLOS ONE   8 ( 7 )   e67326   2013年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Increased stabilization of mRNA coding for key cancer genes can contribute to invasiveness. This is achieved by down-regulation of exosome cofactors, which bind to 3'-UTR in cancer-related genes. Here, we identified amphiregulin, an EGFR ligand, as a target of WD repeat protein Monad, a component of R2TP/prefoldin-like complex, in MDA-MB-231 breast cancer cells. Monad specifically interacted with both the 3'-UTR of amphiregulin mRNA and the RNA degrading exosome, and enhanced decay of amphiregulin transcripts. Knockdown of Monad increased invasion and this effect was abolished with anti-amphiregulin neutralizing antibody. These results suggest that Monad could prevent amphiregulin-mediated invasion by degrading amphiregulin mRNA.

    DOI: 10.1371/journal.pone.0067326

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  • The R2TP complex: discovery and functions. 査読

    Kakihara Y, Houry WA

    Biochimica et biophysica acta   1823 ( 1 )   101 - 107   2012年1月

  • Alternative Oligomeric States of the Yeast Rvb1/Rvb2 Complex Induced by Histidine Tags 査読

    Kevin L. Y. Cheung, Jennifer Huen, Yoshito Kakihara, Walid A. Houry, Joaquin Ortega

    JOURNAL OF MOLECULAR BIOLOGY   404 ( 3 )   478 - 492   2010年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD  

    Rvb1 and Rvb2 are essential AAA(+) (ATPases associated with diverse cellular activities) helicases, which are important components of critical complexes such as chromatin remodeling and telomerase complexes. The oligomeric state of the Rvb proteins has been controversial. Independent studies from several groups have described the yeast and human Rvb1/Rvb2 complex both as a single and as a double hexameric ring complex. We found that histidine-tagged constructs of yeast Rvb proteins employed in some of these studies induced the assembly of double hexameric ring Rvb1/Rvb2 complexes. Instead, untagged versions of these proteins assemble into single hexameric rings. Furthermore, purified endogenous untagged Rvb1/Rvb2 complexes from Saccharomyces cerevisiae were also found as single hexameric rings, similar to the complexes assembled in vitro from the purified untagged components. These results demonstrate that some of the differences between the reported structures are caused by histidine tags and imply that further studies on the purified proteins should be carried out using untagged constructs. (c) 2010 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.jmb.2010.10.003

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  • Rvb1-Rvb2: essential ATP-dependent helicases for critical complexes 査読

    Jennifer Huen, Yoshito Kakihara, Francisca Ugwu, Kevin L. Y. Cheung, Joaquin Ortega, Walid A. Houry

    BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE   88 ( 1 )   29 - 40   2010年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS  

    DOI: 10.1139/O09-122

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  • An atlas of chaperone-protein interactions in Saccharomyces cerevisiae: implications to protein folding pathways in the cell 査読

    Yunchen Gong, Yoshito Kakihara, Nevan Krogan, Jack Greenblatt, Andrew Emili, Zhaolei Zhang, Walid A. Houry

    MOLECULAR SYSTEMS BIOLOGY   5   2009年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Molecular chaperones are known to be involved in many cellular functions, however, a detailed and comprehensive overview of the interactions between chaperones and their cofactors and substrates is still absent. Systematic analysis of physical TAP-tag based protein-protein interactions of all known 63 chaperones in Saccharomyces cerevisiae has been carried out. These chaperones include seven small heat-shock proteins, three members of the AAA+ family, eight members of the CCT/TRiC complex, six members of the prefoldin/GimC complex, 22 Hsp40s, 1 Hsp60, 14 Hsp70s, and 2 Hsp90s. Our analysis provides a clear distinction between chaperones that are functionally promiscuous and chaperones that are functionally specific. We found that a given protein can interact with up to 25 different chaperones during its lifetime in the cell. The number of interacting chaperones was found to increase with the average number of hydrophobic stretches of length between one and five in a given protein. Importantly, cellular hot spots of chaperone interactions are elucidated. Our data suggest the presence of endogenous multicomponent chaperone modules in the cell. Molecular Systems Biology 5: 275; published online 16 June 2009; doi: 10.1038/msb.2009.26

    DOI: 10.1038/msb.2009.26

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  • Molecular chaperone Hsp90 stabilizes Pih1/Nop 17 to maintain R2TP complex activity that regulates snoRNA accumulation 査読

    Rongmin Zhao, Yoshito Kakihara, Anna Gribun, Jennifer Huen, Guocheng Yang, May Khanna, Michael Costanzo, Renee L. Brost, Charles Boone, Timothy R. Hughes, Christopher M. Yip, Walid A. Houry

    JOURNAL OF CELL BIOLOGY   180 ( 3 )   563 - 578   2008年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ROCKEFELLER UNIV PRESS  

    Hsp90 is a highly conserved molecular chaperone that is involved in modulating a multitude of cellular processes. In this study, we identify a function for the chaperone in RNA processing and maintenance. This functionality of Hsp90 involves two recently identified interactors of the chaperone: Tah 1 and Pih1/Nop17. Tah1 is a small protein containing tetra tricopeptide repeats, whereas Pih1 is found to be an unstable protein. Tah1 and Pih1 bind to the essential helicases Rvb1 and Rvb2 to form the R2TP complex, which we demonstrate is required for the correct accumulation of box C/D small nucleolar ribonucleoproteins. Together with the Tah1 cofactor, Hsp90 functions to stabilize Pih1. As a consequence, the chaperone is shown to affect box C/D accumulation and maintenance, especially under stress conditions. Hsp90 and R2TP proteins are also involved in the proper accumulation of box H/ACA small nucleolar RNAs.

    DOI: 10.1083/icb.200709061

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  • Screening of drugs that suppress Ste11 MAPKKK activation in yeast identified a c-Abl tyrosine kinase inhibitor 査読

    Takao Kitagawa, Yuko Hashizume, Tatsuhiko Murakane, Emi Koga, Yuki Nomura, Yoshito Kakihara, Ayako Fujieda, Motoyuki Uchida, Hidetoshi Takahashi, Hisashi Hoshida, Rinji Akada

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   71 ( 3 )   772 - 782   2007年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    The yeast MAPKKK Ste11 activates three MAP kinase pathways, including pheromone signaling, osmo-sensing, and pseudohyphal/invasive growth pathways. We identified two chemical compounds, BTB03006 and GK03225, that suppress growth defects induced by Ste11 activation in diploid yeast cells. BTB03006, but not GK03225, was found to suppress growth defects induced by both a-factor and Ste4 G(beta) overexpression in the pheromone signaling pathway, suggesting that GK03225 is an osmosensing pathway-specific inhibitor. We also performed genome-wide suppressor analysis for Ste11 activation, using a yeast deletion strains collection, and identified PBS2 and HOG1, and several genes associated with chaperone functions, which represent potential target proteins of the drugs screened from Ste11 activation. GK03225 possesses an Iressa-like quinazoline ring structure, and its chemical analog, 11N-078, suppresses c-Abl human tyrosine kinase activity. These results suggest that drug screening in yeast can identify human tyrosine kinase inhibitors and other drugs for human diseases.

    DOI: 10.1271/bbb.60610

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  • PCR-mediated seamless gene deletion and marker recycling in Saccharomyces cerevisiae 査読

    R Akada, T Kitagawa, S Kaneko, D Toyonaga, S Ito, Y Kakihara, H Hoshida, S Morimura, A Kondo, K Kida

    YEAST   23 ( 5 )   399 - 405   2006年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOHN WILEY & SONS LTD  

    Repeated gene manipulations can be performed in yeast by excision of an introduced marker. Cassette modules containing a marker flanked by two direct repeat sequences of hisG or loxP have often been used for marker recycling, but these leave one copy of the repeats in the chromosome after excision. Genomic copies of a repeat can cause increased mistargeting of constructs containing the same repeats or unexpected chromosomal rearrangements via intra- or interchromosomal recombi nations. Here, we describe a novel marker recycling procedure that leaves no scar in the genome, which we have designated seamless gene deletion. A 40 base sequence derived from an adjacent region to the targeted locus was placed in an integrating construct to generate direct repeats after integration. Seamless HIS3 deletion was achieved via a PCR fragment that consisted of a URA3 marker attached to a 40 base repeat-generating sequence flanked by HIS3 targeting sequences at both ends. Transformation of the designed construct resulted in his3 disruption and the generation of 40 base direct repeats on both sides of URA3 in the targeted locus. The resulting his3::URA3 disruptants were plated on 5-fluoroorotic acid medium to select for URA3 loss. All the selected colonies had lost URA3 precisely by recombination between the repeats, resulting in his3 deletion without any extraneous sequences left behind in the chromosome. Copyright (c) 2006 John Wiley & Sons, Ltd.

    DOI: 10.1002/yea.1365

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  • Cost-saving design of PCR primers containing additional sequences 査読

    Yoshito Kakihara, Yasunobu Matsuura, Hisashi Hoshida, Yoshinori Nishizawa, Rinji Akada

    ITE letters   6 ( 2 )   135 - 139   2005年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Overlapping omt1(+) and omt2(+) genes are required for spore wall maturation in Schizosaccharomyces pombe 査読

    Y Kakihara, K Nabeshima, A Hirata, H Nojima

    GENES TO CELLS   8 ( 6 )   547 - 558   2003年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING LTD  

    Background: Overlapping genes that are transcribed from the same genomic regions are rare in eukaryotes and to date few detailed functional analyses have been reported.
    Results: We report here three novel overlapping transcripts that are specifically expressed during meiosis of Schizosaccharomyces pombe . They are denoted as omt1 (+) , omt2 (+) and omt3 (+) after o verlapping m eiotic transcripts. omt1 (+) encodes a 12-kDa protein and omt2 (+) encodes a 11-kDa protein with homology to the bifunctional mammalian protein DCoH/PCBD. omt3 (+) does not have a significant open reading frame. The omt2 (+) transcript overlaps with both the omt1 (+) and omt3 (+) transcripts but the latter two transcripts do not overlap. omt1Delta and omt2Delta but not omt3Delta failed to form mature spore walls. The Omt1-GFP and Omt2-GFP fusion proteins localized to the outside and the inside of the spore walls, respectively. The sporulation-specific protein Meu10 and the spore wall components were abnormally localized in the spore walls of omt1Delta and omt2Delta .
    Conclusion: The overlapping genes omt1 (+) and omt2 (+) express functional proteins that participate in spore wall maturation, indicating that gene overlap does not affect the physiological functions of the proteins encoded by these genes. Generation of overlapped RNA may be due to loose regulation of transcription termination during meiosis of S. pombe .

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  • Meu10 is required for spore wall maturation in Schizosaccharomyces pombe 査読

    T Tougan, Y Chiba, Y Kakihara, A Hirata, H Nojima

    GENES TO CELLS   7 ( 2 )   217 - 231   2002年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING LTD  

    Background: Many genes are meiosis and/or sporulation-specifically transcribed during this process. Isolation and analysis of these genes might help us to understand how meiosis and sporulation are regulated. For this purpose, we have isolated a large number of cDNA clones from Schizosaccharomyces pombe whose expression is up-regulated during meiosis.
    Results: We have isolated meu10(+) gene, which encodes 416 amino acids and bears homology to SPS2 of Saccharomyces cerevisiae. A strain whose meu10(+) gene has been deleted forms no viable spores. Thin-section electron micrographs showed that the meu10Delta strain has abnormally formed spore walls, and then they disrupt, allowing cytoplasmic material to escape. The Meu10-GFP fusion protein is localized to the spore periphery, thereafter returned to the cytoplasm after sporulation. Meu10-GFP localization to the spore wall was almost normal in the bgs2Delta or chs1Delta mutants that lack 1,3-beta-glucan or chitin, respectively. In contrast, 1,3-beta-glucan is abnormally localized in meu10Delta cells. Meu10 has an N-terminal domain with homology to the mammalian insulin receptor and a C-terminal domain with a transmembrane motif. Mutants whose N-terminal or C-terminal domain was truncated were severely defective for sporulation.
    Conclusions: Meu10 is a spore wall component and plays a pivotal role in the formation of the mature spore wall structure.

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  • A novel meiosis-specific protein of fission yeast, Meu13p, promotes homologous pairing independently of homologous recombination 査読

    K Nabeshima, Y Kakihara, Y Hiraoka, H Nojima

    EMBO JOURNAL   20 ( 14 )   3871 - 3881   2001年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Meiotic homologous pairing is crucial to proper homologous recombination, which secures subsequent reductional chromosome segregation. We have identified a novel meiosis-specific protein of fission yeast Schizosaccharomyces pombe, Meu13p, to be a molecule that is required for proper homologous pairing and recombination. Rec12p (homologue of Saccharomyces cerevisiae Spo11p), which is essential for the initiation of meiotic recombination, is also shown for the first time to participate in the pairing process of S. pombe. Meu13p, however, contributes to pairing through a recombination-independent mechanism, as disruption of the meu13(+) gene reduces pairing whether the rec12(+) gene is deleted or not. We also demonstrate a dynamic nature of homologous pairing in living meiotic cells, which is markedly affected by meu13 deletion. Meu13p is not required for telomere clustering and the nuclear movement process, which are well known requirements for efficient pairing in S. pombe. Based on these results, together with the localization of Meu13p on meiotic chromatin, we propose that Meu13p directly promotes proper homologous pairing and recombination.

    DOI: 10.1093/emboj/20.14.3871

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  • Comprehensive isolation of meiosis-specific genes identifies novel proteins and unusual non-coding transcripts in Schizosaccharomyces pombe 査読

    T Watanabe, K Miyashita, TT Saito, T Yoneki, Y Kakihara, K Nabeshima, YA Kishi, C Shimoda, H Nojima

    NUCLEIC ACIDS RESEARCH   29 ( 11 )   2327 - 2337   2001年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    In order to isolate meiosis-specific genes in Schizosaccharomyces pombe, we have constructed a subtracted cDNA library enriched in clones whose expression is enhanced during meiosis induced by nitrogen starvation. Using northern blot analysis, we isolated 31 kinds of clones whose expression was induced in a meiosis/sporulation-specific manner. We comprehensively named them meu after meiotic expression upregulated, The transcription of 20 meu genes was found to be dependent on the mei4+ gene, which encodes a transcription factor required for the progression of meiosis, DNA sequencing indicated that most of the meu genes encode novel proteins, Notably, five of the meu genes harbor no apparent protein coding sequences, and the transcripts form stable hairpin structures, suggesting that they may generate non-coding RNAs or antisense RNAs, The results presented here imply that RNAs are also important for the comprehensive characterization of genomic expression.

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  • Characterization of rec7, an early meiotic recombination gene in Schizosaccharomyces pombe 査読

    M Molnar, S Parisi, Y Kakihara, H Nojima, A Yamamoto, Y Hiraoka, A Bozsik, M Sipiczki, J Kohli

    GENETICS   157 ( 2 )   519 - 532   2001年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:GENETICS  

    rec7 is involved in intra- and intergenic meiotic recombination in all tested regions of the genome of the fission yeast Schizosaccharomyces pombe. Segregational analysis in a rec7 gene disruption mutant revealed frequent occurrence of two-spored asci. Spores giving rise to diploid colonies were shown to derive from skipping of the second meiotic division. Nondisjunction of homologous chromosomes at the first meiotic division was also frequent. The cytological structures and processes, such as formation of linear elements, pairing of homologous chromosomes, and clustering of telomeres and centromeres, are regular in the mutant. Northern blot experiments revealed meiosis-specific expression of rec7. Screening of a meiotic cDNA library also identified transcripts from the opposite strand in the rec7 region. A Rec7-GFP fusion protein was localized in the nucleus of whole cells before karyogamy, during prophase, and after meiosis I. On spreads of prophase nuclei approximately 50 foci of Rec7-GFP were counted. Some of the observed phenotypes of the disruption mutant and the N-terminal sequence homology suggest that Rec7p is a functional homolog of Rec114p of Saccharomyces cerevisae. The observed phenotypes of the disruption and the appearance of Rec7-GFP in mating haploid cells and after meiosis I are consistent with Rec7p functions before, during, and after meiotic prophase.

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MISC

  • Reptinは胎仔上皮におけるDNA損傷応答を介して器官形成を制御する

    目黒史也, 目黒史也, 目黒史也, 柿原嘉人, 川崎真依子, 川崎勝盛, 川崎勝盛, 丹原惇, 丹原惇, トゥラカナン スッパラック, 工藤武久, 工藤武久, 山田茜, 山田茜, 前田健康, 多部田康一, 佐伯万騎男, 大峡淳

    新潟歯学会雑誌   50 ( 2 )   2020年

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  • 日本酒によるストレス誘発性の咬筋侵害応答の軽減効果は日本酒含有エタノールの直接作用ではない

    中谷 暢佑, 柿原 嘉人, 清水 志保, 黒瀬 雅之, 佐伯 万騎男, 高木 律男, 山村 健介, 岡本 圭一郎

    Journal of Oral Biosciences Supplement   2018   260 - 260   2018年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • ROCK阻害剤の骨代謝および矯正学的歯の移動への影響

    中田 樹里, 柿原 嘉人, 秋葉 陽介, 江口 香里, 丹原 惇, 大倉 麻里子, 加藤 寛子, 泉 健次, 佐伯 万騎男, 齋藤 功

    新潟歯学会雑誌   47 ( 2 )   120 - 120   2017年12月

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    記述言語:日本語   出版者・発行元:新潟歯学会  

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  • ROCK阻害剤による骨形成促進メカニズムの解析

    中田 樹里, 柿原 嘉人, 丹原 惇, 佐伯 万騎男, 齋藤 功

    日本矯正歯科学会大会プログラム・抄録集   76回   184 - 184   2017年10月

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    記述言語:日本語   出版者・発行元:(公社)日本矯正歯科学会  

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  • 『酒は百薬の長』の根拠を科学的に解明するストレス誘発性の咬筋侵害受容反応に対する日本酒の影響について

    岡本 圭一郎, 中谷 暢佑, 黒瀬 雅之, 柿原 嘉人, 木口 哲郎, 長谷川 真奈, 藤井 規孝, 佐伯 万騎男, 高木 律男, 山村 健介

    Journal of Oral Biosciences Supplement   2017   462 - 462   2017年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • セロトニン再取り込み阻害薬は繰り返しストレスによる咬筋の侵害受容反応の増強を抑制する

    中谷 暢佑, 黒瀬 雅之, 清水 志保, 柿原 嘉人, 木口 哲郎, 長谷川 真奈, 佐伯 万騎男, 高木 律男, 山村 健介, 岡本 圭一郎

    Journal of Oral Biosciences Supplement   2017   463 - 463   2017年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • 分子シャペロンR2TPの口腔扁平上皮癌進展における作用機序の解析

    木口 哲郎, 柿原 嘉人, 山崎 学, 高木 律男, 佐伯 万騎男

    Journal of Oral Biosciences Supplement   2017   256 - 256   2017年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • ROCK阻害剤の骨代謝への影響とその作用機序の解析

    中田 樹里, 秋葉 陽介, 江口 香里, 丹原 惇, 齋藤 功, 柿原 嘉人, 佐伯 万騎男

    日本骨代謝学会学術集会プログラム抄録集   35回   184 - 184   2017年7月

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    記述言語:日本語   出版者・発行元:(一社)日本骨代謝学会  

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  • 破骨細胞分化に影響を与える薬剤のスクリーニングとその作用機序の解析

    中田 樹里, 柿原 嘉人, 秋葉 陽介, 丹原 惇, 齋藤 功, 佐伯 万騎男

    日本骨代謝学会学術集会プログラム抄録集   34回   207 - 207   2016年7月

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    記述言語:日本語   出版者・発行元:(一社)日本骨代謝学会  

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  • リボソーム合成制御因子R2TPの口腔扁平上皮癌進展における作用機序の解析

    木口哲郎, 木口哲郎, 柿原嘉人, 山崎学, 永田昌毅, 高木律男, 佐伯万騎男

    日本薬理学会北部会プログラム・抄録集   67th   64   2016年

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    記述言語:日本語  

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  • 破骨細胞の分化を誘導する小分子化合物の探索

    西川 実沙, 柿原 嘉人, 秋葉 陽介, 江草 宏, 佐伯 万騎男

    Journal of Oral Biosciences Supplement   2015   546 - 546   2015年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • 破骨細胞分化に影響を与える薬剤の探索

    中田 樹里, 柿原 嘉人, 丹原 惇, 齋藤 功, 江草 宏, 佐伯 万騎男

    日本骨代謝学会学術集会プログラム抄録集   33回   196 - 196   2015年7月

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    記述言語:日本語   出版者・発行元:(一社)日本骨代謝学会  

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  • 破骨細胞分化に影響を与える薬剤のケミカルライブラリースクリーニング

    中田樹里, 中田樹里, 柿原嘉人, 秋葉陽介, 丹原惇, 齋藤功, 江草宏, 佐伯万騎男

    日本薬理学会北部会プログラム・抄録集   66th   53   2015年

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  • 破骨細胞の分化を誘導する小分子化合物の探索

    西川実沙, 柿原嘉人, 秋葉陽介, 江草宏, 佐伯万騎男

    Journal of Oral Biosciences Supplement (Web)   2015   2015年

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  • The R2TP complex: Discovery and functions

    Yoshito Kakihara, Walid A. Houry

    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH   1823 ( 1 )   101 - 107   2012年1月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ELSEVIER SCIENCE BV  

    The two closely related AAA + family ATPases Rvb1 and Rvb2 are part of several critical multiprotein complexes, and, thus, are involved in a wide range of cellular processes including chromatin remodelling, telomerase assembly, and snoRNP biogenesis. It was found that Rvb1 and Rvb2 form a tight functional complex with Pih1 (Protein interacting with Hsp90) and Tah1 (TPR-containing protein associated with Hsp90), which are two Hsp90 interactors. We named the complex R2TP. The complex was originally isolated from Saccharomyces cerevisiae and was, subsequently, identified in mammalian cells. R2TP was found to be required for box C/D snoRNP biogenesis in yeast and mammalian cells. More recently, several studies revealed that the complex is also involved in multiple biological processes including apoptosis, phosphatidylinositol-3 kinase-related protein kinase (PIKK) signalling, and RNA polymerase II assembly. In this review, we describe the discovery of the complex and discuss the emerging critical roles that R2TP plays in distinct cellular processes. This article is part of a Special Issue entitled: AAA ATPases: structure and function. (C) 2011 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.bbamcr.2011.08.016

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  • Comprehensive isolation of meiosis-specific genes identifies novel proteins and unusual non-coding transcripts in Schizosaccharomyces pombe.

    T Watanabe, K Miyashita, T Saito, T Yoneki, Y Kakihara, K Nabeshima, C Shimoda, H Nojima

    YEAST   18   S58 - S58   2001年8月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JOHN WILEY & SONS LTD  

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  • 分裂酵母Meu13は減数分裂特異的に発現し,減数分裂前期の相同染色体の秩序立った空間的配置を促進する

    鍋島建太郎, 柿原嘉人, 平岡泰, 野島博

    日本分子生物学会年会プログラム・講演要旨集   23rd   270   2000年11月

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担当経験のある授業科目

  • 日本酒学A-1

    2021年
    -
    現在
    機関名:新潟大学

  • 日本酒学A-2

    2021年
    -
    現在
    機関名:新潟大学

  • 人体のしくみ

    2020年
    -
    現在
    機関名:新潟大学

  • 日本酒学B

    2020年
    -
    現在
    機関名:新潟大学

  • 歯科薬理学

    2018年
    -
    現在
    機関名:新潟大学

  • 薬理学

    2015年
    -
    現在
    機関名:新潟大学

  • 基礎科学演習

    2015年
    -
    2016年
    機関名:新潟大学

  • 組織工学実習

    2015年
    -
    2016年
    機関名:新潟大学

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