Papers - KAWAUCHI Keiko
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Loss of p53 function promotes DNA damage-induced formation of nuclear actin filaments. Reviewed International journal
Takeru Torii, Wataru Sugimoto, Katsuhiko Itoh, Natsuki Kinoshita, Masaya Gessho, Toshiyuki Goto, Ikuno Uehara, Wataru Nakajima, Yemima Budirahardja, Daisuke Miyoshi, Takahito Nishikata, Nobuyuki Tanaka, Hiroaki Hirata, Keiko Kawauchi
Cell death & disease 14 ( 11 ) 766 - 766 2023.11
Joint Work
Authorship：Last author, Corresponding author
Tumor suppressor p53 plays a central role in response to DNA damage. DNA-damaging agents modulate nuclear actin dynamics, influencing cell behaviors; however, whether p53 affects the formation of nuclear actin filaments remains unclear. In this study, we found that p53 depletion promoted the formation of nuclear actin filaments in response to DNA-damaging agents, such as doxorubicin (DOXO) and etoposide (VP16). Even though the genetic probes used for the detection of nuclear actin filaments exerted a promotive effect on actin polymerization, the detected formation of nuclear actin filaments was highly dependent on both p53 depletion and DNA damage. Whilst active p53 is known to promote caspase-1 expression, the overexpression of caspase-1 reduced DNA damage-induced formation of nuclear actin filaments in p53-depleted cells. In contrast, co-treatment with DOXO and the pan-caspase inhibitor Q-VD-OPh or the caspase-1 inhibitor Z-YVAD-FMK induced the formation of nuclear actin filament formation even in cells bearing wild-type p53. These results suggest that the p53-caspase-1 axis suppresses DNA damage-induced formation of nuclear actin filaments. In addition, we found that the expression of nLifeact-GFP, the filamentous-actin-binding peptide Lifeact fused with the nuclear localization signal (NLS) and GFP, modulated the structure of nuclear actin filaments to be phalloidin-stainable in p53-depleted cells treated with the DNA-damaging agent, altering the chromatin structure and reducing the transcriptional activity. The level of phosphorylated H2AX (γH2AX), a marker of DNA damage, in these cells also reduced upon nLifeact-GFP expression, whilst details of the functional relationship between the formation of nLifeact-GFP-decorated nuclear actin filaments and DNA repair remained to be elucidated. Considering that the loss of p53 is associated with cancer progression, the results of this study raise a possibility that the artificial reinforcement of nuclear actin filaments by nLifeact-GFP may enhance the cytotoxic effect of DNA-damaging agents in aggressive cancer cells through a reduction in gene transcription.
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Development of a pseudo-cellular system to quantify specific interactions determining G-quadruplex function in cells. Reviewed International journal
Journal of the American Chemical Society 146 ( 12 ) 8005 - 8015 2024.2
Joint Work
Publisher：Journal of the American Chemical Society
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Inhibitory Effects of Shikonin Dispersion, an Extract of Lithospermum erythrorhizon Encapsulated in β-1,3-1,6 Glucan, on Streptococcus mutans and Non-Mutans Streptococci. Reviewed International journal
Ryota Nomura, Yuto Suehiro, Fumikazu Tojo, Saaya Matayoshi, Rena Okawa, Masakazu Hamada, Shuhei Naka, Michiyo Matsumoto-Nakano, Rika Unesaki, Kazuya Koumoto, Keiko Kawauchi, Takahito Nishikata, Tatsuya Akitomo, Chieko Mitsuhata, Masatoshi Yagi, Toshiro Mizoguchi, Koki Fujikawa, Taizo Taniguchi, Kazuhiko Nakano
International journal of molecular sciences 25 ( 2 ) 2024.1
Shikonin is extracted from the roots of Lithospermum erythrorhizon, and shikonin extracts have been shown to have inhibitory effects on several bacteria. However, shikonin extracts are difficult to formulate because of their poor water solubility. In the present study, we prepared a shikonin dispersion, which was solubilized by the inclusion of β-1,3-1,6 glucan, and analysed the inhibitory effects of this dispersion on Streptococcus mutans and non-mutans streptococci. The shikonin dispersion showed pronounced anti-S. mutans activity, and inhibited growth of and biofilm formation by this bacterium. The shikonin dispersion also showed antimicrobial and antiproliferative effects against non-mutans streptococci. In addition, a clinical trial was conducted in which 20 subjects were asked to brush their teeth for 1 week using either shikonin dispersion-containing or non-containing toothpaste, respectively. The shikonin-containing toothpaste decreased the number of S. mutans in the oral cavity, while no such effect was observed after the use of the shikonin-free toothpaste. These results suggest that shikonin dispersion has an inhibitory effect on S. mutans and non-mutans streptococci, and toothpaste containing shikonin dispersion may be effective in preventing dental caries.
DOI： 10.3390/ijms25021075
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Inhibitory Effect of Adsorption of Streptococcus mutans onto Scallop-Derived Hydroxyapatite. Reviewed International journal
Momoko Usuda, Mariko Kametani, Masakazu Hamada, Yuto Suehiro, Saaya Matayoshi, Rena Okawa, Shuhei Naka, Michiyo Matsumoto-Nakano, Tatsuya Akitomo, Chieko Mitsuhata, Kazuya Koumoto, Keiko Kawauchi, Takahito Nishikata, Masatoshi Yagi, Toshiro Mizoguchi, Koki Fujikawa, Taizo Taniguchi, Kazuhiko Nakano, Ryota Nomura
International journal of molecular sciences 24 ( 14 ) 2023.7
Hydroxyapatite adsorbs various substances, but little is known about the effects on oral bacteria of adsorption onto hydroxyapatite derived from scallop shells. In the present study, we analyzed the effects of adsorption of Streptococcus mutans onto scallop-derived hydroxyapatite. When scallop-derived hydroxyapatite was mixed with S. mutans, a high proportion of the bacterial cells adsorbed onto the hydroxyapatite in a time-dependent manner. An RNA sequencing analysis of S. mutans adsorbed onto hydroxyapatite showed that the upregulation of genes resulted in abnormalities in pathways involved in glycogen and histidine metabolism and biosynthesis compared with cells in the absence of hydroxyapatite. S. mutans adsorbed onto hydroxyapatite was not killed, but the growth of the bacteria was inhibited. Electron microscopy showed morphological changes in S. mutans cells adsorbed onto hydroxyapatite. Our results suggest that hydroxyapatite derived from scallop shells showed a high adsorption ability for S. mutans. This hydroxyapatite also caused changes in gene expression related to the metabolic and biosynthetic processes, including the glycogen and histidine of S. mutans, which may result in a morphological change in the surface layer and the inhibition of the growth of the bacteria.
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The iron chelator deferriferrichrysin induces paraptosis via extracellular-signal-regulated kinase activation in cancer cells Reviewed International coauthorship
Kinoshita N, Gessho M, Torii T, Ashida Y, Akamatsu M, Guo AK, Lee S, Katsuno T, Nakajima W, Budirahardja Y, Miyoshi D, Todokoro T, Ishida H, Nishikata T, Kawauchi K
Genes to Cells 28 ( 9 ) 653 - 662 2023.6
Authorship：Last author, Corresponding author
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Simple and fast screening for structure-selective G-quadruplex ligands. Reviewed International journal
Yoshiki Hashimoto, Yoshiki Imagawa, Kaho Nagano, Ryuichi Maeda, Naho Nagahama, Takeru Torii, Natsuki Kinoshita, Nagisa Takamiya, Keiko Kawauchi, Hisae Tatesishi-Karimata, Naoki Sugimoto, Daisuke Miyoshi
Chemical communications (Cambridge, England) 59 ( 33 ) 4891 - 4894 2023.4
Joint Work
Structural selectivity of G-quadruplex ligands is essential for cellular applications since there is an excess of nucleic acids forming duplex structures compared to G-quadruplex structures in living cells. In this study, we developed new structure-selective G-quadruplex ligands utilizing a simple and fast screening system. The affinity, selectivity, enzymatic inhibitory activity and cytotoxicity of the structure-selective G-quadruplex ligands were demonstrated along with a structural selectivity-cytotoxicity relationship of G-quadruplex ligands.
DOI： 10.1039/d3cc00556a
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Controlling liquid-liquid phase separation of G-quadruplex-forming RNAs in a sequence-specific manner. Reviewed International journal
Mitsuki Tsuruta, Takeru Torii, Kazuki Kohata, Keiko Kawauchi, Hisae Tateishi-Karimata, Naoki Sugimoto, Daisuke Miyoshi
Chemical communications (Cambridge, England) 58 ( 93 ) 12931 - 12934 2022.11
Joint Work
We constructed a minimum liquid-liquid phase separation model system to form liquid droplets using only G-quadruplex-forming oligonucleotides and R- and G-rich oligopeptides. We found that the G-quadruplex structure is an essential component for RNA to form droplets with the peptide. Based on this model system and our findings, droplet redissolution via structure transition from a G-quadruplex to a duplex was achieved in a sequence-specific manner.
DOI： 10.1039/d2cc04366a
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Intramolecular G-quadruplex-hairpin loop structure competition of a GC-rich exon region in the TMPRSS2 gene Reviewed International journal
Wataru Sugimoto, Natsuki Kinoshita, Minori Nakata, Tatsuya Ohyama, Hisae Tateishi-Karimata, Takahito Nishikata, Naoki Sugimoto, Daisuke Miyoshi, Keiko Kawauchi
Chemical Communications 58 ( 1 ) 48 - 51 2022.1
Joint Work
Authorship：Last author, Corresponding author Publisher：Royal Society of Chemistry (RSC)
We identified cytosine-rich regions adjacent to guanine-rich regions in the TMPRSS2 gene, which showed structural competition between a G-quadruplex and a hairpin loop. Furthermore, this competition significantly affected transcription efficiency.
DOI： 10.1039/d1cc05523b
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Anti-Malignant Effect of Tensile Loading to Adherens Junctions in Cutaneous Squamous Cell Carcinoma Cells Reviewed International journal
Dobrokhotov O, Sunagawa M, Torii T, Mii S, Kawauch K, Enomoto A, Sokabe M, Hirata H.
Frontiers in Cell and Developmental Biology 11 2021.11
Joint Work
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Detection of Intracellular Reactive Oxidative Species Using the Fluorescent Probe Hydroxyphenyl Fluorescein Invited Reviewed International journal
Methods Mol Biol. 2274 207 - 215 2021.5
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Novel Strategy of Photodynamic Therapy Targeting RAS mRNA with G-Quadruplex Ligands for Cancer Treatment Invited Reviewed International journal
Takeru Torii, Wataru Sugimoto, Keiko Kawauchi, Daisuke Miyoshi
Journal of Data Mining in Genomics & Proteomics 11 ( 2 ) 2020.8
Joint Work
Authorship：Corresponding author
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MMP24 as a Target of YAP is a Potential Prognostic Factor in Cancer Patients Reviewed International journal
Wataru Sugimoto, Katsuhiko Ito, Hiroaki Hirata, Yoshinori Abe, Takeru Torii, Yasumasa Mitsui, Yemima Budirahardja, Nobuyuki Tanaka, Keiko Kawauchi
Bioengineering 7 ( 18 ) 1 - 12 2020.2
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DMPK is a new candidate mediator of tumor suppressor p53-dependent cell death. Reviewed International journal
Itoh K, Ebata T, Hirata H, Torii T, Sugimoto W, Onodera K, Nakajima W, Uehara I, Okuzaki D, Yamauchi S, Budirahardja Y, Nishikata T, Tanaka N, Kawauchi K
Molecules (Basel, Switzerland) 24 ( 17 ) 2019.9
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Mechanical regulation of bone homeostasis through p130Cas-mediated alleviation of NF-κB activity. Reviewed International journal
Miyazaki T, Zhao Z, Ichihara Y, Yoshino D, Imamura T, Sawada K, Hayano S, Kamioka H, Mori S, Hirata H, Araki K, Kawauchi K, Shigemoto K, Tanaka S, Bonewald FL, Honda H, Shinohara M, Nagao M, Ogata T, Harada I, Sawada Y.
Science Adv. 5 2019.9
Joint Work
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Mitochondrial protein E2F3d, a distinctive E2F3 product, mediates hypoxia-induced mitophagy in cancer cells. Reviewed International journal
Araki K, Kawauchi K, Sugimoto W, Tsuda D, Oda H, Yoshida R, Ohtani K.
Communications Biol. 6 550 - 561 2019.1
Joint Work
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An anionic phthalocyanine decreases NRAS expression by breaking down its RNA G-quadruplex Reviewed International journal
Kawauchi K, Sugimoto W, Yasui T, Murata K, Itoh K, Takagi K, Tsuruoka T, Akamatsu K, Tateishi-Karimata H, Sugimoto N, Miyoshi D.
Nature Commun. 9 2271 2018.6
Joint Work
Authorship：Lead author, Corresponding author
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Substrate rigidity-dependent positive feedback regulation between YAP and ROCK2. Reviewed International journal
Sugimoto W, Itoh K, Mitsui Y, Ebata T, Fujita H, Hirata H, Kawauchi K
Cell adhesion & migration 12 ( 2 ) 101 - 108 2018.3
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Nanocomposite injectable gels capable of self-replenishing regenerative extracellular microenvironments for in vivo tissue engineering Reviewed International journal
Koji Nagahama, Naho Oyama, Kimika Ono, Atsushi Hotta, Keiko Kawauchi, Takahito Nishikata
Biomater Sci. 6 550 - 561 2018.2
Joint Work
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Destabilization of DNA G-quadruplexes by chemical environment changes during tumor progression facilitates transcription Reviewed International journal
Hisae Tateishi-Karimata, Keiko Kawauchi, Naoki Sugimoto
J Am Chem Soc. 140 642 - 651 2018.1
Joint Work
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NF-kappaB prevents oncogenic Ras-induced b-actin cleavage in p53-deficient cells Reviewed
Wataru Sugimoto, Katsuhiko Itoh, Toshiya Kotari, Alvin K. Guo,Takahiro Ebata, Hiroaki Hirata, Keiko Kawauchi
International Journal of Cancer & Cellular Biology Research 2 ( 1 ) 15 - 18 2017.5