長岡 仁

J-GLOBALへ         更新日: 19/07/02 02:42
 
アバター
研究者氏名
長岡 仁
 
ナガオカ ヒトシ
所属
岐阜大学
部署
医学系研究科 医科学専攻 病態制御学講座 分子病態学分野
職名
教授
学位
医学博士(京都大学)
その他の所属
医学系研究科連合創薬医療情報研究科

プロフィール

抗体記憶形成の分子機構/高親和性スイッチ型抗体遺伝子をもつ記憶Bリンパ球や長期生存形質細胞の形成維持機構を分子レベルで解明する。

研究分野

 
 

経歴

 
2011年
 - 
2014年
岐阜大学 医学(系)研究科(研究院) 教授
 
1993年4月
 - 
1994年3月
京都大学医学部付属病院
 
1994年4月
 - 
2000年3月
国立感染症研究所
 
1998年4月
 - 
2001年3月
Howard Hughes Medical Institute, the Rockefeller University
 
2001年1月
 - 
2011年3月
京都大学医学研究科
 

学歴

 
1983年4月
 - 
1989年3月
山口大学医学部  
 
1989年4月
 - 
1993年3月
京都大学医学研究科  
 

論文

 
Srinontong P, Wu Z, Sato K, Nagaoka H, Maekawa Y
Biochemical and biophysical research communications      2018年10月   [査読有り]
Ohashi T, Aoki M, Tomita H, Akazawa T, Sato K, Kuze B, Mizuta K, Hara A, Nagaoka H, Inoue N, Ito Y
Cancer science   108(6) 1128-1134   2017年6月   [査読有り]
Sato K, Kimura M, Sugiyama K, Nishikawa M, Okano Y, Nagaoka H, Nagase T, Kitade Y, Ueda H
The Journal of biological chemistry   291(48) 25227-25238   2016年11月   [査読有り]
Katsuya Sato, Hiroaki Handa, Masashi Kimura, Yukio Okano, Hitoshi Nagaoka, Takahiro Nagase, Tsuyoshi Sugiyama, Yukio Kitade, Yukio Kitade, Hiroshi Ueda, Hiroshi Ueda
Cellular Signalling   25(1) 41-49   2013年1月   [査読有り]
FLJ00018/PLEKHG2 is a guanine nucleotide exchange factor for the Rho family small GTPases. FLJ00018 is directly activated by heterotrimeric G protein Gβγ subunits. Using two-hybrid screening, we have identified non-muscle cytosolic actin as a bind...
Le Thi Huong, Le Thi Huong, Maki Kobayashi, Mikiyo Nakata, Go Shioi, Hitoshi Miyachi, Tasuku Honjo, Hitoshi Nagaoka
PLoS ONE   8(4) e61433   2013年   [査読有り]
The Aicda gene encodes activation-induced cytidine deaminase (AID). Aicda is strongly transcribed in activated B cells to diversify immunoglobulin genes, but expressed at low levels in various other cells in response to physiological or pathologic...
Kawamata Toyotaka, Lu Jun, Sato Tadayuki, Tanaka Masafumi, Nagaoka Hitoshi, Agata Yasutoshi, Toyoshima Takae, Yokoyama Kazuaki, Oyaizu Naoki, Nakamura Naoya, Ando Kiyoshi, Tojo Arinobu, Kotani Ai
Blood   119(13) 3123-7   2012年3月   [査読有り]
Activation-induced cytidine deaminase (AID) is essential for class switch recombination and somatic hypermutation. Its deregulated expression acts as a genomic mutator that can contribute to the development of various malignancies. During treatmen...
Honjo Tasuku, Kobayashi Maki, Begum Nasim, Kotani Ai, Sabouri Somayeh, Nagaoka Hitoshi
Advances in cancer research   113 1-44   2012年   [査読有り]
Activation-induced cytidine deaminase (AID), which is both essential and sufficient for forming antibody memory, is also linked to tumorigenesis. AID is found in many B lymphomas, in myeloid leukemia, and in pathogen-induced tumors such as adult T...
Qin, H., Suzuki, K., Nakata, M., Chikuma, S., Izumi, N., Thi Huong, L., Maruya, M., Fagarasan, S., Busslinger, M., Honjo, T., and Nagaoka, H.
PLoS One   6(12) e29141   2011年12月   [査読有り]
Activation-induced cytidine deaminase (AID), produced by the Aicda gene, is essential for the immunoglobulin gene (Ig) alterations that form immune memory. Using a Cre-mediated genetic system, we unexpectedly found CD4 + T cells that had expressed...
Okazaki IM(Kyoto University),Natsume Tohru(National Institute of Advanced Industrial Science and Technology),Iemura Shun-Ichiro(National Institute of Advanced Industrial Science and Technology),Honjo Tasuku(Kyoto University),Okawa Katsuya(Kyowa Hakko Kirin Co.),Kobayashi Maki(Kyoto university),Yoshikawa Kiyotsugu(Dana-Farber CancerInstitute),Kawamoto Shimpei(RIKEN Research Center),Nagaoka Hitoshi(Gifu University),Shinkura Reiko(Nagahama Institute of Bioscience and Technology),Kitawaki Yoko(Kyoto University),Taniguchi Hisaaki(University of Tokushima)
Proc Natl Acad Sci U S A   108(19) 7920-7925   2011年5月   [査読有り]
Activation-induced cytidine deaminase (AID) is shown to be essential and sufficient to induce two genetic alterations in the Ig loci: class switch recombination (CSR) and somatic hypermutation (SHM). However, it is still unknown how a single-molec...
Nagaoka Hitoshi, Tran Thinh Huy, Kobayashi Maki, Aida Masatoshi, Honjo Tasuku
International immunology   22(4) 227-35   2010年4月   [査読有り]
Activation-induced cytidine deaminase (AID) is essential and sufficient to accomplish class-switch recombination and somatic hypermutation, whichare two genetic events required for the generation of antibody-mediated memory responses. However, AID...
Tran Thinh Huy, Nakata Mikiyo, Suzuki Keiichiro, Begum Nasim A, Shinkura Reiko, Fagarasan Sidonia, Honjo Tasuku, Nagaoka Hitoshi
Nature immunology   11(2) 148-54   2010年2月   [査読有り]
Activation-induced cytidine deaminase (AID) is essential for the generation of antibodymemory but also targets oncogenes, among other genes. We investigated the transcriptional regulation of Aicda (which encodes AID) in class switch-inducible CH12...
Kobayashi Maki, Aida Masatoshi, Nagaoka Hitoshi, Begum Nasim A, Kitawaki Yoko, Nakata Mikiyo, Stanlie Andre, Doi Tomomitsu, Kato Lucia, Okazaki Il-mi, Shinkura Reiko, Muramatsu Masamichi, Kinoshita Kazuo, Honjo Tasuku
Proceedings of the National Academy of Sciences of the United States of America   106(52) 22375-80   2009年12月   [査読有り]
To initiate class switch recombination (CSR) activation-induced cytidine deaminase (AID) induces staggered nick cleavage in the S region, which lies 5'to each Ig constant region gene and is rich in palindromic sequences. Topoisomerase 1 (Top1) con...
Sabouri Zahra, Okazaki Il-Mi, Shinkura Reiko, Begum Nasim, Nagaoka Hitoshi, Tsuchimoto Daisuke, Nakabeppu Yusaku, Honjo Tasuku
International immunology   21(8) 947-55   2009年8月   [査読有り]
The DNA cleavage step in both the class switch recombination (CSR) and somatic hypermutation (SHM) of Ig genes is initiated by activation-induced cytidine deaminase (AID). However, the detailed mechanisms of the DNA strand cleavage in SHM and CSR ...
Doi Tomomitsu, Kato Lucia, Ito Satomi, Shinkura Reiko, Wei Min, Nagaoka Hitoshi, Wang Jishu, Honjo Tasuku
Proceedings of the National Academy of Sciences of the United States of America   106(8) 2758-63   2009年2月   [査読有り]
Activation-induced cytidine deaminase (AID) is an essential factor for the class switch recombination (CSR) and somatic hypermutation (SHM) of Ig genes. CSR and SHM are initiated by AID-induced DNA breaks in the S and V regions, respectively. Beca...
Sidonia Fagarasan, Masamichi Muramatsu, Keiichiro Suzuki, Hitoshi Nagaoka, Hiroshi Hiai, Tasuku Honjo
Science   298(5597) 1424-1427   2002年11月   [査読有り]
Activation-induced cytidine deaminase (AID) plays an essential role in class switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes. We report here that deficiency in AID results in the development of hyperplasia of iso...
W. Yu, H. Nagaoka, Z. Misulovin, E. Meffre, H. Suh, M. Jankovic, N. Yannoutsos, R. Casellas, E. Besmer, F. Papavasiliou, X. Qin, M. C. Nussenzweig
Cold Spring Harbor Symposia on Quantitative Biology   64 207-210   1999年12月
Amy Reichlin, Anna Gazumyan, Hitoshi Nagaoka, Kathrin H. Kirsch, Manfred Kraus, Klaus Rajewsky, Michel C. Nussenzweig, Michel C. Nussenzweig, Michel C. Nussenzweig
Journal of Experimental Medicine   199(6) 855-865   2004年3月   [査読有り]
B cell receptor (BCR) signaling is mediated through immunoglobulin (Ig)α and Igβ a membrane-bound heterodimer. Igα and Igβ are redundant in their ability to support early B cell development, but their roles in mature B cells have not been defined....
Hiroshi Kimoto, Hitoshi Nagaoka, Yoshihiro Adachi, Toshiaki Mizuochi, Takachika Azuma, Takenori Yagi, Tetsutaro Sata, Shin Yonehara, Yasuko Tsunetsugu-Yokota, Masaru Taniguchi, Toshitada Takemori, Toshitada Takemori
European Journal of Immunology   27 268-279
Well-developed germinal centers (GC) contain rapidly dividing surface immunoglobulin-negative (sIg-) B cells (centroblasts), and most of their progeny are sIg+ B cells (centrocytes) in a resting state. It has been predicted that somatic hypermutat...
Ai Kotani, Naoki Kakazu, Tatsuaki Tsuruyama, Il Mi Okazaki, Masamichi Muramatsu, Kazuo Kinoshita, Hitoshi Nagaoka, Daisuke Yabe, Tasuku Honjo
Proceedings of the National Academy of Sciences of the United States of America   104(5) 1616-1620   2007年1月   [査読有り]
Activation-induced cytidine deaminase (AID), which is essential to both class switch recombination and somatic hypermutation of the Ig gene, is expressed in many types of human B cell lymphoma/ leukemia. AID is a potent mutator because it is invol...
Satomi Ito, Hitoshi Nagaoka, Reiko Shinkura, Nasim Begum, Masamichi Muramatsu, Mikiyo Nakata, Tasuku Honjo
Proceedings of the National Academy of Sciences of the United States of America   101(7) 1975-1980   2004年2月   [査読有り]
Activation-induced cytidine deaminase (AID) is a molecule central to initiating class switch recombination, somatic hypermutation, and gene conversion of Ig genes. However, its mechanism to initiate these genetic alterations is still unclear. AID ...
Hitoshi Nagaoka, Masamichi Muramatsu, Namiko Yamamura, Kazuo Kinoshita, Tasuku Honjo, Tasuku Honjo
Journal of Experimental Medicine   195(4) 529-534   2002年2月   [査読有り]
Somatic hypermutation (SHM) and class switch recombination (CSR) cause distinct genetic alterations at different regions of immunoglobulin genes in B lymphocytes: point mutations in variable regions and large deletions in S regions, respectively. ...
Kiyotsugu Yoshikawa, Il mi Okazaki, Tomonori Eto, Kazuo Kinoshita, Masamichi Muramatsu, Hitoshi Nagaoka, Tasuku Honjo
Science   296(5575) 2033-2036   2002年6月   [査読有り]
Activation-induced cytidine deaminase (AID), a putative RNA-editing enzyme, is indispensable for somatic hypermutation (SHM), class switch recombination, and gene conversion of immunoglobulin genes, which indicates a common molecular mechanism for...
Van Thanh Ta, Hitoshi Nagaoka, Nadia Catalan, Anne Durandy, Alain Fischer, Kohsuke Imai, Kohsuke Imai, Shigeaki Nonoyama, Shigeaki Nonoyama, Junko Tashiro, Masaya Ikegawa, Satomi Ito, Kazuo Kinoshita, Masamichi Muramatsu, Tasuku Honjo
Nature Immunology   4(9) 843-848   2003年9月   [査読有り]
Activation-induced cytidine deaminase (AID) is the essential and sole B cell-specific factor required for class-switch recombination (CSR) and somatic hypermutation (SHM). However, it is not known how AID differentially regulates these two indepen...
Tasuku Honjo, Hitoshi Nagaoka, Reiko Shinkura, Masamichi Muramatsu
Nature Immunology   6(7) 655-661   2005年7月   [査読有り]
The limitations of genomic information forced our ancestors to adopt a strategy for introducing somatic DNA alterations with the risk of genome instability. Although activation-induced deaminase (AID) is involved in DNA cleavage in somatic hypermu...
Y. Komeno, Y. Komeno, J. Kitaura, J. Kitaura, N. Watanabe-Okochi, N. Watanabe-Okochi, N. Kato, N. Kato, T. Oki, T. Oki, F. Nakahara, F. Nakahara, Y. Harada, H. Harada, R. Shinkura, H. Nagaoka, Y. Hayashi, T. Honjo, T. Kitamura, T. Kitamura
Leukemia   24 1018-1024
Activation-induced cytidine deaminase (AID) diversifies immunoglobulin through somatic hypermutation (SHM) and class-switch recombination (CSR). AID-transgenic mice develop T-lymphoma, indicating that constitutive expression of AID leads to tumori...
Zahra Sabouri, Il mi Okazaki, Il mi Okazaki, Reiko Shinkura, Nasim Begum, Hitoshi Nagaoka, Tasuku Honjo
International Immunology   22 213-214
A. Reichlin, Y. Hu, E. Meffre, H. Nagaoka, S. Gong, M. Kraus, K. Rajewsky, M. C. Nussenzweig
Journal of Experimental Medicine   193 13-23
The B cell receptor (BCR) regulates B cell development and function through immunoglobulin (Ig)α and Igβ, a pair of membrane-bound Ig superfamily proteins, each of which contains a single cytoplasmic immunoreceptor tyrosine activation motif (ITAM)...
Yukiko Misawa, Hitoshi Nagaoka, Hiroshi Kimoto, Yasunori Ishii, Kazuyuki Kitamura, Yasuko Tsunetsugu-Yokota, Masafumi Shibuya, Toshitada Takemori, Toshitada Takemori
European Journal of Immunology   26 2573-2581
CD43 is a major surface sialoprotein on hemopoietic cells, whose extracellular domain is heavily O-glycosylated. The functional role of CD43 in the hemopoietic system is not fully understood; however, it has been suggested that CD43 may have a rol...
Makoto Haino, Hidenori Hayashida, Takashi Miyata, Euy Kyun Shin, Fumihiko Matsuda, Hitoshi Nagaoka, Ryusuke Matsumura, Shigeo Taka-ishi, Yosho Fukita, Junji Fujikura, Tasuku Honjo, Tasuku Honjo
Journal of Biological Chemistry   269 2619-2626
Nucleotide sequences of 64 VH segments within the 3′ 0.8-megabase region of the human immunoglobulin germ line VH locus were compared with trace evolution of human VH segments. Based on alignment of the deduced amino acid sequences of 37 functiona...
Wong Yu, Hitoshi Nagaoka, Hitoshi Nagaoka, Mila Jankovic, Mila Jankovic, Ziva Misulovin, Ziva Misulovin, Heikyung Suh, Heikyung Suh, Antonius Rolink, Fritz Melchers, Eric Meffre, Eric Meffre, Michel C. Nussenzweig, Michel C. Nussenzweig
Nature   400 682-687
Models of B-cell development in the immune system suggest that only those immature B cells in the bone marrow that undergo receptor editing express V(D)J-recombination-activating genes (RAGs). Here we investigate the regulation of RAG expression i...
Nasim A. Begum, Kazuo Kinoshita, Masamichi Muramatsu, Hitoshi Nagaoka, Reiko Shinkura, Tasuku Honjo
Proceedings of the National Academy of Sciences of the United States of America   101(35) 13003-13007   2004年8月   [査読有り]
Activation-induced cytidine deaminase is required for the DNA cleavage step of Ig class switch recombination (CSR). However, its molecular mechanism is controversial. RNA-editing hypothesis postulates that activation-induced cytidine deaminase dea...
Hitoshi Nagaoka, Satomi Ito, Masamichi Muramatsu, Mikiyo Nakata, Tasuku Honjo
Proceedings of the National Academy of Sciences of the United States of America   102(6) 2022-2027   2005年2月   [査読有り]
Activation-induced cytidine deaminase (AID) is required for the DNA cleavage step of Ig somatic hypermutation (SHM). However, its molecular mechanism is controversial. The RNA editing hypothesis postulates that AID deaminates cytosine in an unknow...
Koshou Wakae, Brad G. Magor, Holly Saunders, Hitoshi Nagaoka, Akemi Kawamura, Kazuo Kinoshita, Tasuku Honjo, Masamichi Muramatsu
International Immunology   18(1) 41-47   2006年1月   [査読有り]
Following activation of mammalian B cells, class switch recombination (CSR) and somatic hypermutation (SHM) of the Ig heavy chain (IgH) gene can improve the functions of the expressed antibodies. Activation-induced cytidine deaminase (AID) is the ...
Nasim A. Begum, Andre Stanlie, Tomomitsu Doi, Yoko Sasaki, Hai Wei Jin, Yong Sung Kim, Hitoshi Nagaoka, Tasuku Honjo
Proceedings of the National Academy of Sciences of the United States of America   106(8) 2752-2757   2009年2月   [査読有り]
Activation-induced cytidine deaminase (AID) introduces DNA cleavage in the Ig gene locus to initiate somatic hypermutation (SHM) and class switch recombination (CSR) in B cells. The DNA deamination model assumes that AID deaminates cytidine (C) on...
Jishu Wang, Reiko Shinkura, Masamichi Muramatsu, Hitoshi Nagaoka, Kazuo Kinoshita, Tasuku Honjo
Journal of Biological Chemistry   281 19115-19123
Activation-induced cytidine deaminase (AID) is essential to all three genetic alterations required for generation of antigen-specific immunoglobulin: class switch recombination, somatic hypermutation, and gene conversion. Here we demonstrate that ...
Jishu Wang, Reiko Shinkura, Masamichi Muramatsu, Hitoshi Nagaoka, Kazuo Kinoshita, Tasuku Honjo
Journal of Biological Chemistry   283(1) 660   2008年1月   [査読有り]
Toyotaka Kawamata, Jun Lu, Tadayuki Sato, Masafumi Tanaka, Hitoshi Nagaoka, Yasutoshi Agata, Takae Toyoshima, Kazuaki Yokoyama, Naoki Oyaizu, Naoya Nakamura, Kiyoshi Ando, Arinobu Tojo, Ai Kotani
Blood   119(13) 3123-3127   2012年3月   [査読有り]
Activation-induced cytidine deaminase (AID) is essential for class switch recombination and somatic hypermutation. Its deregulated expression acts as a genomic mutator that can contribute to the development of various malignancies. During treatmen...
M. Kimura, T. Yoshioka, M. Saio, M. Saio, Y. Banno, H. Nagaoka, Y. Okano, Y. Okano
Cell Death and Disease   4 
Mitotic catastrophe, which refers to cell death or its prologue triggered by aberrant mitosis, can be induced by a heterogeneous group of stimuli, including chromosome damage or perturbation of the mitotic apparatus. We investigated the mechanism ...
Taro Muto, Taro Muto, Il Mi Okazaki, Shuichi Yamada, Yoshimasa Tanaka, Kazuo Kinoshita, Masamichi Muramatsu, Hitoshi Nagaoka, Tasuku Honjo
Proceedings of the National Academy of Sciences of the United States of America   103(8) 2752-2757   2006年2月   [査読有り]
Both class switch recombination (CSR) and somatic hypermutation (SHM) of the Ig genes require the activity of activation-induced cytidine deaminase (AID). Expression of AID is restricted to B cells in the germinal centers of the lymphoid organs, w...
Hitoshi Nagaoka, Hitoshi Nagaoka, Gloria Gonzalez-Aseguinolaza, Moriya Tsuji, Michel C. Nussenzweig, Michel C. Nussenzweig, Michel C. Nussenzweig
Journal of Experimental Medicine   191 2113-2120
Recombination activating gene (RAG) expression in peripheral B cells increases after immunization with (4-hydroxy-3-nitrophenyl) acetyl coupled to chicken gamma globulin (NP-CGG) in alum. This increase could result from reinduction of RAG expressi...
Fumihiko Matsuda, Euy Kyun Shin, Yasuhiko Hirabayashi, Hitoshi Nagaoka, Michihiro C. Yoshida, Michihiro C. Yoshida, Shu Quin Zong, Tasuku Honjo
EMBO Journal   9 2501-2506
We have studied the organization of variable region (V) genes of the human immunoglobulin heavy chain (H) by cosmid cloning. We isolated two independent immunoglobulin D5 clusters (D5-a and D5-b) from cosmid libraries of the human genome. Restrict...
Euy Kyun Shin, Fumihiko Matsuda, Hitoshi Nagaoka, Yosho Fukita, Takashi Imai, Kazushige Yokoyama, Eiichi Soeda, Tasuku Honjo, Tasuku Honjo
EMBO Journal   10 3641-3645
We have constructed the physical map of the 3′ region of the human immunoglobulin heavy chain variable region (VH) genes. DNA segments extending to 200 kb upstream of the JH segment were isolated in two YAC clones. Five VH segments were identified...
Hitoshi Nagaoka, Hitoshi Nagaoka, Yoshimasa Takahashi, Reiko Hayashi, Tohru Nakamura, Tohru Nakamura, Kumiko Ishii, Junichiro Matsuda, Atsuo Ogura, Yumiko Shirakata, Hajime Karasuyama, Tetsuo Sudo, Shin Ichi Nishikawa, Takeshi Tsubata, Tsuguo Mizuochi, Toshihiko Asano, Hitoshi Sakano, Toshitada Takemori, Toshitada Takemori
Journal of Experimental Medicine   192 171-181
Ras is essential for the transition from early B cell precursors to the pro-B stage, and is considered to be involved in the signal cascade mediated by pre-B cell antigen receptors. To examine the role of p21(ras) in the late stage of B cell diffe...
Hitoshi Nagaoka, Kazuo Ozawa, Fumihiko Matsuda, Hidenori Hayashida, Ryusuke Matsumura, Makoto Haino, Euy Kyun Shin, Yosho Fukita, Takashi Imai, Rakesh Anand, Kazushige Yokoyama, Toshihiko Eki, Eiichi Soeda, Tasuku Honjo
Genomics   22 189-197
We studied the organization and origin of three orphon regions, VH-F, D5-a, and D5-b, of the human immunoglobulin heavy-chain gene using yeast artificial chromosomes. VH-F and two D5 regions were mapped to chromosome bands 16p11 and 15q11-q12, res...
Nasim A. Begum, Nakako Izumi, Momoko Nishikori, Hitoshi Nagaoka, Reiko Shinkura, Tasuku Honjo
Journal of Biological Chemistry   282(1) 731-742   2007年1月   [査読有り]
Activation-induced cytidine deaminase (AID) and uracil DNA glycosylase (UNG) are required for class switch recombination (CSR). AID is involved in the DNA cleavage step of CSR, but the precise role of UNG is not yet understood. Mutations and delet...
Reiko Shinkura, Satomi Ito, Nasim A. Begum, Hitoshi Nagaoka, Masamichi Muramatsu, Kazuo Kinoshita, Yishimasa Sakakibara, Hiroko Hijikata, Tasuku Honjo
Nature Immunology   5(7) 707-712   2004年7月   [査読有り]
Activation-induced cytidine deaminase (AID) is essential for class-switch recombination (CSR) and somatic hypermutation (SHM). Mutants with changes in the C-terminal region of AID retain SHM but lose CSR activity. Here we describe five mutants wit...
Ryusuke Matsumura, Fumihiko Matsuda, Hitoshi Nagaoka, Junji Fujikura, Euy Kyun Shin, Euy Kyun Shin, Yosho Fukita, Yosho Fukita, Makoto Haino, Tasuku Honjo, Tasuku Honjo, Tasuku Honjo
Journal of Immunology   152 660-666
The organization and evolution of the 0.8-Mb JH-proximal region in the human Ig VH locus were studied by mapping DNA fragments hybridized to non-repetitive intergenic probes and by determination of the content and distribution of repetitive sequen...
F. Matsuda, E. K. Shin, H. Nagaoka, R. Matsumura, M. Haino, Y. Fukita, S. Taka-ishi, T. Imai, J. H. Riley, R. Anand, E. Soeda, T. Honjo
Nature Genetics   3 88-94
We have constructed the physical map of the 0.8 megabase DNA fragment which contains the 3' 64 variable region (V) gene segments of the human immunoglobulin heavy chain (H) locus. The organization of the V(H) locus showed several features that ind...
Nasim A. Begum, Kazuo Kinoshita, Naoki Kakazu, Masamichi Muramatsu, Hitoshi Nagaoka, Reiko Shinkura, Detlev Biniskiewicz, Laurie A. Boyer, Rudolf Jaenisch, Tasuku Honjo
Science   305(5687) 1160-1163   2004年8月   [査読有り]
Activation-induced cytidine deaminase (AID) is required for the DNA cleavage step in immunoglobulin class switch recombination (CSR). AID is proposed to deaminate cytosine to generate uracil (U) in either mRNA or DNA. In the second instance, DNA c...
Masaki Kashiwada, Yumiko Shirakata, Jun Ichiro Inoue, Hiroyasu Nakano, Kenji Okazaki, Ko Okumura, Tadashi Yamamoto, Hitoshi Nagaoka, Toshitada Takemori, Toshitada Takemori
Journal of Experimental Medicine   187 237-244
CD40 activates nuclear factor kappa B (NFκB) and the mitogen-activated protein kinase (MAPK) subfamily, including extracellular signal-regulated kinase (ERK). The CD40 cytoplasmic tail interacts with tumor necrosis factor receptor-associated facto...

Misc

 
Ilmi Okazaki, Kiyotsugu Yoshikawa, Kiyotsugu Yoshikawa, Kazuo Kinoshita, Masamichi Muramatsu, Hitoshi Nagaoka, Tasuku Honjo
Annals of the New York Academy of Sciences   987 1-8
Activation-induced cytidine deaminase (AID), a putative RNA-editing cytidine deaiminase that is expressed strictly in activated B cells, is indispensable in three apparently distinct genetic alterations of immunoglobulin genes - namely, class swit...
Tasuku Honjo, Tasuku Honjo, Tasuku Honjo, Tasuku Honjo, Masamichi Muramatsu, Hitoshi Nagaoka, Kazuo Kinoshita, Reiko Shinkura
Proceedings of the Japan Academy Series B: Physical and Biological Sciences   82 104-120
The immune system has adopted somatic DNA alterations to overcome the limitations of the genomic information. Activation induced cytidine deaminase (AID) is an essential enzyme to regulate class switch recombination (CSR), somatic hypermutation (S...
Masamichi Muramatsu, Masamichi Muramatsu, Hitoshi Nagaoka, Reiko Shinkura, Nasim A. Begum, Nasim A. Begum, Tasuku Honjo
Advances in Immunology   94 1-36
Discovery of activation-induced cytidine deaminase (AID) paved a new path to unite two genetic alterations induced by antigen stimulation; class switch recombination (CSR) and somatic hypermutation (SHM). AID is now established to cleave specific ...
Velizar Shivarov, Reiko Shinkura, Tomomitsu Doi, Nasim A. Begum, Hitoshi Nagaoka, Il Mi Okazaki, Satomi Ito, Taichiro Nonaka, Kazuo Kinoshita, Tasuku Honjo
Philosophical Transactions of the Royal Society B: Biological Sciences   364 569-575
Activation-induced cytidine deaminase (AID) is the essential enzyme inducing the DNA cleavage required for both somatic hypermutation and class switch recombination (CSR) of the immunoglobulin gene. We originally proposed the RNA-editing model for...
Hitoshi Nagaoka, Thinh Huy Tran, Maki Kobayashi, Masatoshi Aida, Tasuku Honjo
International Immunology   22 227-235
Activation-induced cytidine deaminase (AID) is essential and sufficient to accomplish class-switch recombination and somatic hypermutation, which are two genetic events required for the generation of antibody-mediated memory responses. However, AI...

講演・口頭発表等

 
転写因子BATF-IRF4複合体による遺伝子座の高次構造形成とAID遺伝子発現調節
佐藤克哉 掘賢一郎 安田一 長岡仁.
第91回日本生化学会大会   2018年9月24日   日本生化学会
CRISPR/Cas9を用いた抗体遺伝子改変酵素AIDの発現調節機構の解析
掘賢一郎 佐藤克哉 金山佳史 安田一 長屋州宣 長岡仁.
BMB2015   2015年12月4日   日本生化学会 日本分子生物学会
抗体遺伝子に免疫記憶を刻む分子AID [招待有り]
長岡 仁.
第37回免疫カンファレンス   2011年11月   免疫カンファレンス
AID遺伝子が発現するT細胞サブセットはIL-10を発現し加齢とともに蓄積するユニークなサブセットである
長岡 仁.
第84回日本生化学会大会   2011年9月   日本生化学会
RNF8によるPlk1タンパク質の現象とがん細胞における異常
木村正志
第84回日本生化学会大会   2011年9月   日本生化学会
Activation-induced cytidine deaminase expression in CD4+ T cells is associated with a unique IL-10-producing subset that increases with age
長岡 仁.
国際シンポジウム 細胞運命制御   2012年11月   文部科学省新学術領域「細胞運命制御」

担当経験のある科目

 
 

競争的資金等の研究課題

 
文部科学省: 科学研究費補助金(基盤研究(C))
研究期間: 2014年 - 2016年    代表者: 長岡 仁
文部科学省: 科学研究費補助金(挑戦的萌芽研究)
研究期間: 2011年 - 2013年    代表者: 長岡 仁
効率的にBリンパ球最終分化の分子機構を解析する為に、cre依存的に不可逆的に遺伝子制御を可能とする事を目指したウィルスベクターを作製した。また、Cre発現マウスとして、Bリンパ球最終分化に重要な分子AIDの遺伝子を用いたCre発現トランスジェニックマウスを解析した。Cre発現をモニターできるレポーターマウスと掛け合わせたものを用い、生理的条件下でのAID発現を個体レベルでシングルセルレベルで解析し、活性化Bリンパ球以外にTリンパ球等でもAIDが発現する事を明らかにした。更に、AIDの遺伝子...
文部科学省: 科学研究費補助金(新学術領域研究(研究領域提案型))
研究期間: 2011年 - 2012年    代表者: 長岡 仁
本研究は、免疫応答においてIgM陽性のナイーブBリンパ球が活性化され胚中心細胞を経てクラススイッチした抗親和型抗体を産生する形質細胞及びメモリー細胞へ分化する際の終末分化のメカニズムを解明する事を目的とする。Bリンパ球移入解析系の構築に資するため、活性化Bリンパ球特異的に誘導され抗体遺伝子のクラススイッチ組み換えと体細胞突然変異に必須の酵素AIDの遺伝子Aicdaのコード領域にcreを導入した190kbのマウスゲノムBACクローンを導入されたトランスジェニックマウスで、Creレポーターと内...
文部科学省: 科学研究費補助金(基盤研究(C))
研究期間: 2008年 - 2011年    代表者: 長岡 仁
AIDは抗体遺伝子の改変や細胞の腫瘍化に係るタンパク質で、その発現制御と作用機構を分子レベルで解析した。AIDの遺伝子Aicdaの制御にエンハンサーとサイレンサーとして機能するエレメントをin vitro及びin vivoで明らかにし、そこに結合する因子を同定した。また、AID分子にヒストンシャペロンSpt6が結合する事また、AIDのC末端ドメインは抗体遺伝子のクラススイッチ組み換えでDNA修復の過程に関与する事を明らかにした。これらの知見はAIDの機能やその破綻による細胞がん化過程の理解...
文部科学省: 科学研究費補助金(特定領域研究)
研究期間: 2006年 - 2007年    代表者: 長岡 仁
AIDはがん遺伝子に変異を入れ、細胞腫瘍化に於いて病的に機能している可能性が高い。本研究は元来免疫グロブリン(Ig)に変異を蓄積する事で有効な感染防御の獲得に寄与すべきAIDが、何故がん遺伝子を標的としてしまうのか、又それが腫瘍の誘因と成るのか、進展を助長するのか等特にリンパ腫の発生の観点から明らかにする事を目的とする。AIDを強制発現させた時にIg可変(V)領域遺伝子に導入される体細胞突然変異(SHM)の効率が高いヒトBリンパ球系株BL-2とほとんど見られないNalm6で、V領域遺伝子部...

社会貢献活動

 
斐太高等学校学部学科説明会
【】  斐太高等学校  斐太高等学校  2016年5月26日 - 2016年5月26日
斐太高等学校において医学部医学科の概要説明を行うとともに研究内容及び活動等を高校生に説明を行う,
名古屋市立大学最新医学講座オープンカレッジ
【講師】  名古屋市立大学  講演会  (名古屋市立大学)  2017年11月17日 - 2017年11月17日
2
本庶氏ノーベル賞 がん免疫療法発見 指導受けた県内研究者ら喜び「待ち焦がれていた」
【その他】  岐阜新聞  マスコミ報道  2018年10月2日