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38 results on '"Okabe, Atsushi"'

1. Enhancer infestation drives tumorigenic activation of inactive B compartment in Epstein-Barr virus-positive nasopharyngeal carcinoma

Author

Mizokami, Harue, Okabe, Atsushi, Choudhary, Ruchi, Mima, Masato, Saeda, Kenta, Fukuyo, Masaki, Rahmutulla, Bahityar, Seki, Motoaki, Goh, Boon-Cher, Kondo, Satoru, Dochi, Hirotomo, Moriyama-Kita, Makiko, Misawa, Kiyoshi, Hanazawa, Toyoyuki, Tan, Patrick, Yoshizaki, Tomokazu, Fullwood, Melissa Jane, and Kaneda, Atsushi

Published
2024
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2. An integrative transcriptional logic model of hepatic insulin resistance

Author

Kitamoto, Takumi, Kuo, Taiyi, Okabe, Atsushi, Kaneda, Atsushi, and Accili, Domenico

Subjects
Biochemistry and Cell Biology, Biological Sciences, Liver Disease, Nutrition, Digestive Diseases, Genetics, Diabetes, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Metabolic and endocrine, Animals, Fasting, Forkhead Box Protein O1, Gene Expression Regulation, Insulin Resistance, Liver, Male, Mice, Mice, Inbred C57BL, Models, Biological, Transcription, Genetic, diabetes, insulin sensitizers, drug failures, chromatin structure, animal models of human disease
Abstract

Abnormalities of lipid/lipoprotein and glucose metabolism are hallmarks of hepatic insulin resistance in type 2 diabetes. The former antedate the latter, but the latter become progressively refractory to treatment and contribute to therapeutic failures. It's unclear whether the two processes share a common pathogenesis and what underlies their progressive nature. In this study, we investigated the hypothesis that genes in the lipid/lipoprotein pathway and those in the glucose metabolic pathway are governed by different transcriptional regulatory logics that affect their response to physiologic (fasting/refeeding) as well as pathophysiologic cues (insulin resistance and hyperglycemia). To this end, we obtained genomic and transcriptomic maps of the key insulin-regulated transcription factor, FoxO1, and integrated them with those of CREB, PPAR-α, and glucocorticoid receptor. We found that glucose metabolic genes are primarily regulated by promoter and intergenic enhancers in a fasting-dependent manner, while lipid genes are regulated through fasting-dependent intron enhancers and fasting-independent enhancerless introns. Glucose genes also showed a remarkable transcriptional resiliency (i.e., the ability to compensate following constitutive FoxO1 ablation through an enrichment of active marks at shared PPAR-α/FoxO1 regulatory elements). Unexpectedly, insulin resistance and hyperglycemia were associated with a "spreading" of FoxO1 binding to enhancers and the emergence of unique target sites. We surmise that this unusual pattern correlates with the progressively intractable nature of hepatic insulin resistance. This transcriptional logic provides an integrated model to interpret the combined lipid and glucose abnormalities of type 2 diabetes.

Published
2021

6. Chemical catalyst manipulating cancer epigenome and transcription.

Author

Yamanashi, Yuki, Takamaru, Shinpei, Okabe, Atsushi, Kaito, Satoshi, Azumaya, Yuto, Kamimura, Yugo R., Yamatsugu, Kenzo, Kujirai, Tomoya, Kurumizaka, Hitoshi, Iwama, Atsushi, Kaneda, Atsushi, Kawashima, Shigehiro A., and Kanai, Motomu

Subjects
ELONGATION factors (Biochemistry), GENETIC engineering, HISTONE acetylation, GENETIC transcription, CANCER chemotherapy
Abstract

The number and variety of identified histone post-translational modifications (PTMs) are continually increasing. However, the specific consequences of each histone PTM remain largely unclear, primarily due to the lack of methods for selectively and rapidly introducing a desired histone PTM in living cells without genetic engineering. Here, we report the development of a cell-permeable histone acetylation catalyst, BAHA-LANA-PEG-CPP44, which selectively enters leukemia cells, binds to chromatin, and acetylates H2BK120 of endogenous histones in a short reaction time. Time-course analyses of this in-cell catalytic reaction revealed that H2BK120 acetylation attenuates the chromatin binding of negative elongation factor E (NELFE), an onco-transcription factor. This H2BK120 acetylation-mediated removal of NELFE from chromatin reshapes transcription, slows leukemia cell viability, and reduces their tumorigenic potential in mice. Therefore, this histone acetylation catalyst provides a unique tool for elucidating the time-resolved consequences of histone PTMs and may offer a modality for cancer chemotherapy. Here, the authors develop a cell-permeable chemical catalyst that acetylates histone H2BK120 in leukemia cells, attenuates NELFE chromatin binding, reprograms transcription, and reduces the tumorigenic potential of leukemia cells in mice. [ABSTRACT FROM AUTHOR]

Published
2025
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7. Identification of AR-V7 downstream genes commonly targeted by AR/AR-V7 and specifically targeted by AR-V7 in castration resistant prostate cancer

Author

Sugiura, Masahiro, Sato, Hiroaki, Okabe, Atsushi, Fukuyo, Masaki, Mano, Yasunobu, Shinohara, Ken-ichi, Rahmutulla, Bahityar, Higuchi, Kosuke, Maimaiti, Maihulan, Kanesaka, Manato, Imamura, Yusuke, Furihata, Tomomi, Sakamoto, Shinichi, Komiya, Akira, Anzai, Naohiko, Kanai, Yoshikatsu, Luo, Jun, Ichikawa, Tomohiko, and Kaneda, Atsushi

Published
2021
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8. Dose‐dependent effects of histone methyltransferase NSD2 on site‐specific double‐strand break repair.

Author

Iwasaki, Koh, Tojo, Akari, Kobayashi, Haruka, Shimizu, Kai, Kamimura, Yoshitaka, Horikoshi, Yasunori, Fukuto, Atsuhiko, Sun, Jiying, Yasui, Manabu, Honma, Masamitsu, Okabe, Atsushi, Fujiki, Ryoji, Nakajima, Nakako Izumi, Kaneda, Atsushi, Tashiro, Satoshi, Sassa, Akira, and Ura, Kiyoe

Subjects
HOMOLOGOUS recombination, HISTONE methylation, GENETIC transcription, METHYLTRANSFERASES, THYMIDINE, DNA repair, DOUBLE-strand DNA breaks
Abstract

Histone modifications are catalyzed and recognized by specific proteins to regulate dynamic DNA metabolism processes. NSD2 is a histone H3 lysine 36 (H3K36)‐specific methyltransferase that is associated with both various transcription regulators and DNA repair factors. Specifically, it has been implicated in the repair of DNA double‐strand breaks (DSBs); however, the role of NSD2 during DSB repair remains enigmatic. Here, we show that NSD2 does not accumulate at DSB sites and that it is not further mobilized by DSB formation. Using three different DSB repair reporter systems, which contained the endonuclease site in the active thymidine kinase gene (TK) locus, we demonstrated separate dose‐dependent effects of NSD2 on homologous recombination (HR), canonical‐non‐homologous end joining (c‐NHEJ), and non‐canonical‐NHEJ (non‐c‐NHEJ). Endogenous NSD2 has a role in repressing non‐c‐NHEJ, without affecting DSB repair efficiency by HR or total NHEJ. Furthermore, overexpression of NSD2 promotes c‐NHEJ repair and suppresses HR repair. Therefore, we propose that NSD2 has functions in chromatin integrity at the active regions during DSB repair. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Integrated enhancer regulatory network by enhancer–promoter looping in gastric cancer

Author

Zhu, Tianhui, primary, Okabe, Atsushi, additional, Usui, Genki, additional, Fujiki, Ryoji, additional, Komiyama, Daichi, additional, Huang, Kie Kyon, additional, Seki, Motoaki, additional, Fukuyo, Masaki, additional, Abe, Hiroyuki, additional, Ning, Meng, additional, Okada, Tomoka, additional, Minami, Mizuki, additional, Matsumoto, Makoto, additional, Fan, Qin, additional, Rahmutulla, Bahityar, additional, Hoshii, Takayuki, additional, Tan, Patrick, additional, Morikawa, Teppei, additional, Ushiku, Tetsuo, additional, and Kaneda, Atsushi, additional

Published
2024
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10. Aberrant Upregulation of RUNX3 Activates Developmental Genes to Drive Metastasis in Gastric Cancer

Author

Suda, Kazuto, primary, Okabe, Atsushi, additional, Matsuo, Junichi, additional, Chuang, Linda Shyue Huey, additional, Li, Ying, additional, Jangphattananont, Nawaphat, additional, Mon, Naing Naing, additional, Myint, Khine Nyein, additional, Yamamura, Akihiro, additional, So, Jimmy Bok-Yan, additional, Voon, Dominic Chih-Cheng, additional, Yang, Henry, additional, Yeoh, Khay Guan, additional, Kaneda, Atsushi, additional, and Ito, Yoshiaki, additional

Published
2024
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11. The Link of mRNA and rRNA Transcription by PUF60/FIR through TFIIH/P62 as a Novel Therapeutic Target for Cancer

Author

Kitamura, Kouichi, primary, Hoshino, Tyuji, additional, Okabe, Atsushi, additional, Fukuyo, Masaki, additional, Rahmutulla, Bahityar, additional, Tanaka, Nobuko, additional, Kobayashi, Sohei, additional, Tanaka, Tomoaki, additional, Shida, Takashi, additional, Ueda, Mashiro, additional, Minamoto, Toshinari, additional, Matsubara, Hisahiro, additional, Kaneda, Atsushi, additional, Ishii, Hideshi, additional, and Matsushita, Kazuyuki, additional

Published
2023
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13. Correction: Chromatin Rewiring by Mismatch Repair Protein MSH2 Alters Cell Adhesion Pathways and Sensitivity to BET Inhibition in Gastric Cancer

Author

Nargund, Amrita M., primary, Xu, Chang, additional, Mandoli, Amit, additional, Okabe, Atsushi, additional, Chen, Gao Bin, additional, Huang, Kie Kyon, additional, Sheng, Taotao, additional, Yao, Xiaosai, additional, Teo, Jia Ming Nickolas, additional, Sundar, Raghav, additional, Kok, Yee Jiun, additional, See, Yi Xiang, additional, Xing, Manjie, additional, Li, Zhimei, additional, Yong, Chern Han, additional, Anand, Aparna, additional, Bin Adam Isa, Zul Fazreen, additional, Poon, Lai Fong, additional, Ng, Michelle Shu Wen, additional, Koh, Javier Yu Peng, additional, Ooi, Wen Fong, additional, Tay, Su Ting, additional, Ong, Xuewen, additional, Tan, Angie Lay Keng, additional, Smoot, Duane T., additional, Ashktorab, Hassan, additional, Grabsch, Heike I., additional, Fullwood, Melissa J., additional, Teh, Bin Tean, additional, Bi, Xuezhi, additional, Kaneda, Atsushi, additional, Li, Shang, additional, and Tan, Patrick, additional

Published
2023
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14. [Chiba Medical Society Young Investigator Award Minireview] Epigenetic contribution to tumorigenesis of host cells by Epstein-Barr virus infection

Author

FUJII, Takahiro, OKABE, Atsushi, and KANEDA, Atsushi

Subjects
hemic and lymphatic diseases
Abstract

[ABSTRACT] Epstein-Barr virus (EBV) is known as an oncogenic virus and causes tumors in a variety of tissues, including lymphocytes and epithelial cells. EBV infects host cells latently as an episome and affects the host genome and epigenome while switching between three types of latent stages and a lytic stage. In recent years, the development of analytic methods using next generation sequencing and chromosome conformation capture technologies has enabled us to identify abnormalities at the molecular level in cancer cells. In EBV-positive tumors, pigenetic alterations such as DNA methylation, viral miRNA-mediated expression changes, and aberrations in histone modification and 3D chromatin structure, together with the involvement of EBV, have been revealed by analysis of tumor cells and in vitro EBV infection experiments. Further understanding of host-EBV interactions and their roles in the cancer pathogenesis is expected to lead to the development of revolutionary therapies targeting the epigenome. Here we review epigenetic contribution to tumorigenesis by EBV infection in host cells.

Published
2022

15. Chromatin Rewiring by Mismatch Repair Protein MSH2 Alters Cell Adhesion Pathways and Sensitivity to BET Inhibition in Gastric Cancer

Author

Nargund, Amrita M., primary, Xu, Chang, additional, Mandoli, Amit, additional, Okabe, Atsushi, additional, Chen, Gao Bin, additional, Huang, Kie Kyon, additional, Sheng, Taotao, additional, Yao, Xiaosai, additional, Teo, Jia Ming Nickolas, additional, Sundar, Raghav, additional, Kok, Yee Jiun, additional, See, Yi Xiang, additional, Xing, Manjie, additional, Li, Zhimei, additional, Yong, Chern Han, additional, Anand, Aparna, additional, Bin Adam Isa, Zul Fazreen, additional, Poon, Lai Fong, additional, Ng, Michelle Shu Wen, additional, Koh, Javier Yu Peng, additional, Ooi, Wen Fong, additional, Tay, Su Ting, additional, Ong, Xuewen, additional, Tan, Angie Lay Keng, additional, Smoot, Duane T., additional, Ashktorab, Hassan, additional, Grabsch, Heike I., additional, Fullwood, Melissa J., additional, Teh, Bin Tean, additional, Bi, Xuezhi, additional, Kaneda, Atsushi, additional, Li, Shang, additional, and Tan, Patrick, additional

Published
2022
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16. Activation of EHF via STAT3 phosphorylation by LMP2A in Epstein‐Barr virus–positive gastric cancer

Author

Li, Wenzhe, primary, Okabe, Atsushi, additional, Usui, Genki, additional, Fukuyo, Masaki, additional, Matsusaka, Keisuke, additional, Rahmutulla, Bahityar, additional, Mano, Yasunobu, additional, Hoshii, Takayuki, additional, Funata, Sayaka, additional, Hiura, Nobuhiro, additional, Fukayama, Masashi, additional, Tan, Patrick, additional, Ushiku, Tetsuo, additional, and Kaneda, Atsushi, additional

Published
2021
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17. TET1 upregulation drives cancer cell growth through aberrant enhancer hydroxymethylation of HMGA2 in hepatocellular carcinoma

Author

Shirai, Kiyokazu, primary, Nagae, Genta, additional, Seki, Motoaki, additional, Kudo, Yotaro, additional, Kamio, Asuka, additional, Hayashi, Akimasa, additional, Okabe, Atsushi, additional, Ota, Satoshi, additional, Tsutsumi, Shuichi, additional, Fujita, Takanori, additional, Yamamoto, Shogo, additional, Nakaki, Ryo, additional, Kanki, Yasuharu, additional, Osawa, Tsuyoshi, additional, Midorikawa, Yutaka, additional, Tateishi, Keisuke, additional, Ichinose, Masao, additional, and Aburatani, Hiroyuki, additional

Published
2021
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20. Epstein‐Barr virus‐positive gastric cancer involves enhancer activation through activating transcription factor 3

Author

Asakawa, Yuta, primary, Okabe, Atsushi, additional, Fukuyo, Masaki, additional, Li, Wenzhe, additional, Ikeda, Eriko, additional, Mano, Yasunobu, additional, Funata, Sayaka, additional, Namba, Hiroe, additional, Fujii, Takahiro, additional, Kita, Kazuko, additional, Matsusaka, Keisuke, additional, and Kaneda, Atsushi, additional

Published
2020
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22. Ethyl β-d-glucoside: a novel chemoattractant of Ralstonia solanacearum isolated from tomato root exudates by a bioassay-guided fractionation

Author

Hasegawa, Takuya, Okabe, Atsushi, Kato, Yusuke, Ooshiro, Atsushi, Kawaide, Hiroshi, and Natsume, Masahiro

Subjects
fungi, food and beverages, biochemical phenomena, metabolism, and nutrition, equipment and supplies
Abstract

A chemoattractant of Ralstonia solanacearum isolated from the activated charcoal-adsorbed fraction of tomato root exudates was identified as ethyl β-d-glucopyranoside by instrumental analyses and comparison with synthetic preparations. Ethyl β-D-glucopyranoside showed unambiguous activity at above 1 µmol/disc. Its stereoisomers and D-glucose were inactive. Structure of chemoattractant for Ralstonia solanacearum isolated from tomato root exudates with the guidance of bioassay was identified as ethyl β-D-glucopyranoside.

Published
2018
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23. PHLDA1, another PHLDA family protein that inhibits Akt

Author

Chen, Yu, primary, Takikawa, Masahiro, additional, Tsutsumi, Shuichi, additional, Yamaguchi, Yoko, additional, Okabe, Atsushi, additional, Shimada, Mayuna, additional, Kawase, Tatsuya, additional, Sada, Akane, additional, Ezawa, Issei, additional, Takano, Yuhei, additional, Nagata, Kisaburo, additional, Suzuki, Yutaka, additional, Semba, Kentaro, additional, Aburatani, Hiroyuki, additional, and Ohki, Rieko, additional

Published
2018
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24. Region-specific alteration of histone modification by LSD1 inhibitor conjugated with pyrrole-imidazole polyamide

Author

Alagarswamy, Kokiladevi, primary, Shinohara, Ken-Ichi, additional, Takayanagi, Shihori, additional, Fukuyo, Masaki, additional, Okabe, Atsushi, additional, Rahmutulla, Bahityar, additional, Yoda, Natsumi, additional, Qin, Rui, additional, Shiga, Naoki, additional, Sugiura, Masahiro, additional, Sato, Hiroaki, additional, Kita, Kazuko, additional, Suzuki, Takayoshi, additional, Nemoto, Tetsuhiro, additional, and Kaneda, Atsushi, additional

Published
2018
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28. Single extreme low dose/low dose rate irradiation causes alteration in lifespan and genome instability in primary human cells

Author

Okada, Maki, Okabe, Atsushi, Uchihori, Yukio, Kitamura, Hisashi, Sekine, Emiko, Ebisawa, Satoru, Suzuki, Masao, and Okayasu, Ryuichi

Abstract

To investigate the long term biological effect of extreme low dose ionizing radiation (IR), we irradiated normal human fibroblasts (HFL III) with carbon ions (290 MeV/u, 70 keV/µm) and gamma-rays at 1 mGy (total dose) once at a low dose rate (1 mGy/6-8 h), and observed the cell growth kinetics up to five months by continuous culturing. The growth of carbon irradiated cells started to slow down considerably sooner than that of non-irradiated cells before reaching senescence. In contrast, cells irradiated with gamma-rays under similar conditions did not show significant deviation from the non-irradiated cells. A DNA double strand break (DSB) marker, gammaH2AX foci and a DSB repair marker, phosphorylated DNA-PKcs foci, increased in number when non-irradiated cells reached several passages before senescence. A single low dose/low dose rate carbon ion exposure further raised the numbers of these markers. Furthermore, the numbers of foci for these two markers were significantly reduced after the cells became fully senescent. Our results indicate that high linear energy transfer (LET) radiation (carbon ions) causes different effects than low LET radiation (gamma-rays) even at very low doses and that a single low dose of heavy ion irradiation can affect the stability of the genome many generations after irradiation.

Published
2007

31. Novel p53 target gene FUCA1 encodes a fucosidase and regulates growth and survival of cancer cells

Author

Ezawa, Issei, primary, Sawai, Yuichiro, additional, Kawase, Tatsuya, additional, Okabe, Atsushi, additional, Tsutsumi, Shuichi, additional, Ichikawa, Hitoshi, additional, Kobayashi, Yuka, additional, Tashiro, Fumio, additional, Namiki, Hideo, additional, Kondo, Tadashi, additional, Semba, Kentaro, additional, Aburatani, Hiroyuki, additional, Taya, Yoichi, additional, Nakagama, Hitoshi, additional, and Ohki, Rieko, additional

Published
2016
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32. SCFFbxo22-KDM4A targets methylated p53 for degradation and regulates senescence

Author

Johmura, Yoshikazu, primary, Sun, Jia, additional, Kitagawa, Kyoko, additional, Nakanishi, Keiko, additional, Kuno, Toshiya, additional, Naiki-Ito, Aya, additional, Sawada, Yumi, additional, Miyamoto, Tomomi, additional, Okabe, Atsushi, additional, Aburatani, Hiroyuki, additional, Li, ShengFan, additional, Miyoshi, Ichiro, additional, Takahashi, Satoru, additional, Kitagawa, Masatoshi, additional, and Nakanishi, Makoto, additional

Published
2016
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33. IER5 generates a novel hypo-phosphorylated active form of HSF1 and contributes to tumorigenesis

Author

Asano, Yoshinori, primary, Kawase, Tatsuya, additional, Okabe, Atsushi, additional, Tsutsumi, Shuichi, additional, Ichikawa, Hitoshi, additional, Tatebe, Satoko, additional, Kitabayashi, Issay, additional, Tashiro, Fumio, additional, Namiki, Hideo, additional, Kondo, Tadashi, additional, Semba, Kentaro, additional, Aburatani, Hiroyuki, additional, Taya, Yoichi, additional, Nakagama, Hitoshi, additional, and Ohki, Rieko, additional

Published
2016
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34. Tumor Suppressor miR-22 Determines p53-Dependent Cellular Fate through Post-transcriptional Regulation of p21

Author

Tsuchiya, Naoto, primary, Izumiya, Masashi, additional, Ogata-Kawata, Hiroko, additional, Okamoto, Koji, additional, Fujiwara, Yuko, additional, Nakai, Makiko, additional, Okabe, Atsushi, additional, Schetter, Aaron J., additional, Bowman, Elise D., additional, Midorikawa, Yutaka, additional, Sugiyama, Yasuyuki, additional, Aburatani, Hiroyuki, additional, Harris, Curtis C., additional, and Nakagama, Hitoshi, additional

Published
2011
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37. A distal enhancer of GATA3 regulates Th2 differentiation and allergic inflammation.

Author

Kumagai T, Iwata A, Furuya H, Kato K, Okabe A, Toda Y, Kanai M, Fujimura L, Sakamoto A, Kageyama T, Tanaka S, Suto A, Hatano M, Kaneda A, and Nakajima H

Subjects
Animals, Mice, Humans, Mice, Knockout, Inflammation immunology, Inflammation genetics, Hypersensitivity immunology, Hypersensitivity genetics, Polymorphism, Single Nucleotide, Mice, Inbred C57BL, GATA3 Transcription Factor metabolism, GATA3 Transcription Factor genetics, Th2 Cells immunology, Cell Differentiation immunology, Asthma immunology, Asthma genetics, Asthma pathology, Enhancer Elements, Genetic
Abstract

Asthma is a widespread airway disorder where GATA3-dependent Type-2 helper T (Th2) cells and group 2 innate lymphoid cells (ILC2s) play vital roles. Asthma-associated single nucleotide polymorphisms (SNPs) are enriched in a region located 926-970 kb downstream from GATA3 in the 10p14 (hG900). However, it is unknown how hG900 affects the pathogenesis of allergic airway inflammation. To investigate the roles of the asthma-associated GATA3 enhancer region in experimental allergic airway inflammation, we first examined the correlation between GATA3 expression and the activation of the hG900 region was analyzed by flow cytometry and ChIP-qPCR. We found that The activation of enhancers in the hG900 region was strongly correlated to the levels of GATA3 in human peripheral T cell subsets. We next generated mice lacking the mG900 region (mG900KO mice) were generated by the CRISPR-Cas9 system, and the development and function of helper T cells and ILCs in mG900KO mice were analyzed in steady-state conditions and allergic airway inflammation induced by papain or house dust mite (HDM). The deletion of the mG900 did not affect the development of lymphocytes in steady-state conditions or allergic airway inflammation induced by papain. However, mG900KO mice exhibited reduced allergic inflammation and Th2 differentiation in the HDM-induced allergic airway inflammation. The analysis of the chromatin conformation around Gata3 by circular chromosome conformation capture coupled to high-throughput sequencing (4C-seq) revealed that the mG900 region interacted with the transcription start site of Gata3 with an influencing chromatin conformation in Th2 cells. These findings indicate that the mG900 region plays a pivotal role in Th2 differentiation and thus enhances allergic airway inflammation., Competing Interests: Competing interests statement:The authors declare no competing interest.

Published
2024
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38. RNAi-mediated knockdown showing impaired cell survival in Drosophila wing imaginal disc.

Author

Umemori M, Habara O, Iwata T, Maeda K, Nishinoue K, Okabe A, Takemura M, Takahashi K, Saigo K, Ueda R, and Adachi-Yamada T

Abstract

The genetically amenable organism Drosophila melanogaster has been estimated to have 14,076 protein coding genes in the genome, according to the flybase release note R5.13 (http://flybase.bio.indiana.edu/static_pages/docs/release_notes.html). Recent application of RNA interference (RNAi) to the study of developmental biology in Drosophila has enabled us to carry out a systematic investigation of genes affecting various specific phenotypes. In order to search for genes supporting cell survival, we conducted an immunohistochemical examination in which the RNAi of 2,497 genes was independently induced within the dorsal compartment of the wing imaginal disc. Under these conditions, the activities of a stress-activated protein kinase JNK (c-Jun N-terminal kinase) and apoptosis-executing factor Caspase-3 were monitored. Approximately half of the genes displayed a strong JNK or Caspase-3 activation when their RNAi was induced. Most of the JNK activation accompanied Caspase-3 activation, while the opposite did not hold true. Interestingly, the area activating Caspase-3 was more broadly seen than that activating JNK, suggesting that JNK is crucial for induction of non-autonomous apoptosis in many cases. Furthermore, the RNAi of essential factors commonly regulating transcription and translation showed a severe and cell-autonomous apoptosis but also elicited another apoptosis at an adjacent area in a non-autonomous way. We also found that the frequency of apoptosis varies depending on the tissues.

Published
2009
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