Nagaoka Hitoshi

J-GLOBAL         Last updated: Jul 2, 2019 at 02:42
 
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Name
Nagaoka Hitoshi
Affiliation
Gifu University
Section
Graduate School of Medicine

Profile

Molecular basis of generation and maintenance of antibody memory/To elucidate the molecular mechanisms by which memory B lymphocytes and/or long lived plasma cells were generated and maintained after vaccination.

Research Areas

 
 

Published Papers

 
Srinontong P, Wu Z, Sato K, Nagaoka H, Maekawa Y
Biochemical and biophysical research communications      Oct 2018   [Refereed]
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   Jun 2017   [Refereed]
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   Nov 2016   [Refereed]
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   Jan 2013   [Refereed]
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   [Refereed]
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   Mar 2012   [Refereed]
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...
HonjoTasuku, Kobayashi Maki, Begum Nasim, Kotani Ai, Sabouri Somayeh, Nagaoka Hitoshi
Advances in cancer research   113 1-44   2012   [Refereed]
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   Dec 2011   [Refereed]
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 Cancer Institute),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   May 2011   [Refereed]
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   Apr 2010   [Refereed]
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...
Tran Thinh Huy, Nakata Mikiyo, Suzuki Keiichiro, Begum Nasim A, Shinkura Reiko, Fagarasan Sidonia, Honjo Tasuku, Nagaoka Hitoshi
Nature immunology   11(2) 148-54   Feb 2010   [Refereed]
Activation-induced cytidine deaminase (AID) is essential for the generation of antibody memory but also targets oncogenes, among other genes. We investigated the transcriptional regulation of Aicda (which encodes AID) in class switch-inducible CH1...
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   Dec 2009   [Refereed]
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   Aug 2009   [Refereed]
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 detailedmechanisms of the DNA strand cleavage in SHM and CSR a...
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   Feb 2009   [Refereed]
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   Nov 2002   [Refereed]
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   Dec 1999
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   Mar 2004   [Refereed]
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   Jan 2007   [Refereed]
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   Feb 2004   [Refereed]
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   Feb 2002   [Refereed]
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   Jun 2002   [Refereed]
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   Sep 2003   [Refereed]
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   Jul 2005   [Refereed]
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   Aug 2004   [Refereed]
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   Feb 2005   [Refereed]
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   Jan 2006   [Refereed]
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   Feb 2009   [Refereed]
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   Jan 2008   [Refereed]
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   Mar 2012   [Refereed]
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   Feb 2006   [Refereed]
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   Jan 2007   [Refereed]
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   Jul 2004   [Refereed]
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   Aug 2004   [Refereed]
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...

Conference Activities & Talks

 
Activation-induced cytidine deaminase expression in CD4+ T cells is associated with a unique IL-10-producing subset that increases with age
Hitoshi Nagaoka
国際シンポジウム 細胞運命制御   Nov 2012   文部科学省新学術領域「細胞運命制御」

Research Grants & Projects

 
Ministry of Education, Culture, Sports, Science and Technology: Grants-in-Aid for Scientific Research(挑戦的萌芽研究)
Project Year: 2011 - 2013    Investigator(s): Hitoshi NAGAOKA
We studied the Aicda (activation-induced cytidine deaminase's gene) gene regulation in vivo by using Aicda-cre BAC transgenic system. We found that the Aicda gene is expressed in some mature T cells in periphery in addition to the germinal center ...
Ministry of Education, Culture, Sports, Science and Technology: Grants-in-Aid for Scientific Research(基盤研究(C))
Project Year: 2008 - 2011    Investigator(s): Hitoshi NAGAOKA
AID is the molecule central for Immunoglobulin gene alteration ; its activity is believed to be involved in tumorigenesis in various types of cells. We have analyzed the regulatory elements in/around Aicda, the gene for AID and have determined ess...
Ministry of Education, Culture, Sports, Science and Technology: Grants-in-Aid for Scientific Research(基盤研究(C))
Project Year: 2004 - 2005    Investigator(s): Hitoshi NAGAOKA
B-lymphocytes modify their immunoglobulin genes upon antigen stimulation in helper T-lymphocyte dependent manner. The modifications include somatic hypermutation (SHM) and class switch recombination (CSR), which are molecular basis's of affinity m...
Ministry of Education, Culture, Sports, Science and Technology: Grants-in-Aid for Scientific Research(一般研究(C))
Project Year: 1994 - 1996    Investigator(s): 三沢 幸子, Hitoshi NAGAOKA
CD43 is a major surface sialoprotein on hemopoietic cells, whose extracellular domain is heavily O-glycosilated.The functional role of CD43 in the hemopoietic system is not fully understood ; however, it has been suggested that CD43 may have a rol...
Japan Society for the Promotion of Science: Grants-in-Aid for Scientific Research
Project Year: 2011 - 2013