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Oncology
Chong Wang, Tao Wang, Kang-Jing Li, Ling-Hong Hu, Yue Li, Yu-Zhong Yu, Tao Xie, Sha Zhu, Du-Jiang Fu, Yang Wang, Xian-Zi Zeng, Feng-Ping Liu, Hong Chen, Zhe-Sheng Chen, Ning-Han Feng, Jinghua Liu, Yong Jiang, Shan-Chao Zhao
Summary: The SETD4 protein plays a crucial role in prostate cancer by catalyzing histone lysine methylation and suppressing NUPR1 transcription, leading to the inhibition of Akt signaling pathway and preventing PCa development.
Article
Immunology
Xuyong Chen, Benjamin Sunkel, Meng Wang, Siwen Kang, Tingting Wang, J. N. Rashida Gnanaprakasam, Lingling Liu, Teresa A. Cassel, David A. Scott, Ana M. Munoz-Cabello, Jose Lopez-Barneo, Jun Yang, Andrew N. Lane, Gang Xin, Benjamin Z. Stanton, Teresa W. -M. Fan, Ruoning Wang
Summary: Effective T cell-mediated immune responses require proper allocation of metabolic resources and epigenetic control. Our study revealed that tricarboxylic acid cycle flux fuels biosynthetic processes and controls the ratio of succinate/alpha-ketoglutarate to modulate T cell inflammation. SDH/complex II deficiency in T cells caused proliferation and survival defects when the TCA cycle was truncated, but replenishing the nucleoside pool partially relieved the dependence of T cells on SDH/complex II. SDH deficiency induced a proinflammatory gene signature and promoted T helper 1 and T helper 17 lineage differentiation by increasing succinate/alpha-KG ratio. SDH/complex II plays a role in allocating carbon resources and epigenetic regulation in T cell proliferation and inflammation.
SCIENCE IMMUNOLOGY
(2022)
Article
Cell Biology
Rosari Hernandez-Vicens, Jagreeti Singh, Nomi Pernicone, Tamar Listovsky, Gabi Gerlitz
Summary: Our study suggests that SETDB1 affects microtubule dynamics by interacting with both microtubules and HDAC6 to enhance tubulin deacetylation. These findings provide a novel insight into the cytoplasmic role of SETDB1 in the regulation of microtubule dynamics.
CELL PROLIFERATION
(2022)
Review
Biochemistry & Molecular Biology
Monika Pieniawska, Katarzyna Izykowska
Summary: Histone deacetylases (HDACs) are enzymes that alter chromatin structure, affecting gene expression. They play important roles in T-cell development and function. This review summarizes the current understanding of the role of HDACs in early T-cell development and mature lymphocyte function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Na Li, Hong Yang, Ke Liu, Liwei Zhou, Yuting Huang, Danyan Cao, Yanlian Li, Yaoliang Sun, Aisong Yu, Zhiyan Du, Feng Yu, Ying Zhang, Bingyang Wang, Meiyu Geng, Jian Li, Bing Xiong, Shilin Xu, Xun Huang, Tongchao Liu
Summary: Researchers have developed a potent inhibitor 38 that selectively targets the NSD2-PWWP1 domain. This inhibitor has been shown to affect the expression of genes regulated by NSD2.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Lillian J. Eichner, Stephanie D. Curtis, Sonja N. Brun, Caroline K. McGuire, Irena Gushterova, Joshua T. Baumgart, Elijah Trefts, Debbie S. Ross, Tammy J. Rymoff, Reuben J. Shaw
Summary: HDAC3 plays a critical role in Kras-mutant lung cancer, promoting tumor growth and mediating the expression of target genes, including FGFR1. Inhibition of HDAC3 with entinostat can reverse resistance to the MEK inhibitor trametinib. Combination treatment of entinostat and trametinib shows therapeutic benefit in Kras/LKB1 GEMM.
Article
Oncology
Tiffany M. Tran, Julia Philipp, Jaspal Singh Bassi, Neha Nibber, Jolene M. Draper, Tasha L. Lin, Jayanth Kumar Palanichamy, Amit Kumar Jaiswal, Oscar Silva, May Paing, Jennifer King, Sol Katzman, Jeremy R. Sanford, Dinesh S. Rao
Summary: IGF2BP3 plays a crucial role in MLL-Af4 translocated leukemia, deletion of which significantly improves survival and reduces disease burden in mice. At the cellular and molecular levels, IGF2BP3 regulates leukemia cell survival and proliferation by targeting important genes and influencing both steady-state mRNA levels and pre-mRNA splicing.
Article
Biochemistry & Molecular Biology
Mohammad B. Aljazi, Yuen Gao, Yan Wu, Jin He
Summary: This study reveals that SMYD5 is a specific methyltransferase that catalyzes histone H3K36/K37 mono-methylation in mammalian cells. The genetic deletion of Smyd5 in mouse embryonic stem cells reduces the global level of H3K37me1.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Yuming Cao, Qi Sun, Zhenlie Chen, Jing Lu, Ting Geng, Ling Ma, Yuanzhen Zhang
Summary: Our study revealed that CDKN2AIP is expressed in spermatocytes and spermatids, and plays a role in spermiogenesis and germ cell development. Loss of Cdkn2aip expression in male mice resulted in sperm head defects and age-dependent germ cell loss. Mechanistically, Cdkn2aip deficiency led to synapsis failure and increased apoptosis due to impaired DNA double-strand break repair and crossover formation.
CELL AND BIOSCIENCE
(2022)
Article
Biology
Zhen Sun, Yingpeng Yao, Menghao You, Jingjing Liu, Wenhui Guo, Zhihong Qi, Zhao Wang, Fang Wang, Weiping Yuan, Shuyang Yu
Summary: The kinase PDK1 plays a crucial role in promoting T follicular helper (Tfh) cell differentiation and germinal center responses. PDK1 deficiency in T cells resulted in impaired early differentiation and maintenance of Tfh cells, with downregulation of key Tfh regulators. Mechanistically, ablation of PDK1 led to defective AKT phosphorylation and mTORC1 activation, ultimately impacting Tfh cell differentiation.
Review
Oncology
Stefano Zoroddu, Irene Marchesi, Luigi Bagella
Summary: Muscle differentiation failure may involve epigenetic systems and the PRC2 complex. Research has shown that EZH2 is often deregulated in rhabdomyosarcoma and is associated with tumor malignancy.
CLINICAL EPIGENETICS
(2021)
Article
Chemistry, Medicinal
Joshua S. Alford, John W. Lampe, Dorothy Brach, Richard Chesworth, Kat Cosmopoulos, Kenneth W. Duncan, Sean T. Eckley, Alejandra Raimondi, Thomas V. Riera, Brian Shook, Cuyue Tang, Jennifer Totman, Neil A. Farrow
Summary: The study identified a novel SETD2 inhibitor tool compound suitable for preclinical studies, and further evolution led to compounds appropriate for clinical evaluation. This optimization process resulted in the discovery of EZM0414, a potent and selective inhibitor of SETD2 with good pharmacokinetic properties.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
John W. Lampe, Joshua S. Alford, P. Ann Boriak-Sjodin, Dorothy Brach, Kat Cosmopoulos, Kenneth W. Duncan, Sean T. Eckley, Megan A. Foley, Darren M. Harvey, Vinny Motwani, Michael J. Munchhof, Alejandra Raimondi, Thomas Riera, Cuyue Tang, Michael J. Thomenius, Jennifer Totman, Neil A. Farrow
Summary: EPZ-719, a novel and potent SETD2 inhibitor with high selectivity over other histone methyltransferases, is an attractive tool compound for the interrogation of SETD2 biology.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Wei Cai, Junxun Zhang, Hong Zhou, Xiangxiao Li, Fangzhou Lou, Yang Sun, Zhenyao Xu, Jing Bai, Qianqian Yin, Zhikai Wang, Libo Sun, Xiaojie Cai, Sibei Tang, Yue Wu, Li Fan, Hong Wang, Honglin Wang, Qun Li
Summary: Our study reveals that loss of Pp6 in T-reg cells leads to spontaneous autoinflammation and decreased FoxP3 levels, exacerbating T-reg-related autoinflammation in mice. Mechanistically, Pp6 deficiency affects DNA methylation and Akt signaling, resulting in impaired FoxP3 expression in T-reg cells.
Article
Chemistry, Medicinal
Bin Zhou, Xiaofei Liang, Husheng Mei, Shuang Qi, Zongru Jiang, Aoli Wang, Fengming Zou, Qingwang Liu, Juan Liu, Wenliang Wang, Chen Hu, Yongfei Chen, Zuowei Wang, Beilei Wang, Li Wang, Jing Liu, Qingsong Liu
Summary: EZH2, the catalytic subunit of PRC2, is associated with various malignancies. A novel inhibitor 29 targeting EZH2 with high selectivity and potential therapeutic efficacy has been discovered. It shows promising pharmacokinetic properties and improved efficacy in mouse models, suggesting its potential as a therapeutic candidate for EZH2 mutant cancers.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Ryunosuke Muro, Takeshi Nitta, Kenta Nakano, Tadashi Okamura, Hiroshi Takayanagi, Harumi Suzuki
JOURNAL OF CLINICAL INVESTIGATION
(2018)
Article
Biochemistry & Molecular Biology
Ryunosuke Muro, Takeshi Nitta, Masayuki Kitajima, Toshiyuki Okada, Harumi Suzuki
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2018)
Article
Cell Biology
Soon-Ki Han, Xingyun Qi, Kei Sugihara, Jonathan H. Dang, Takaho A. Endo, Kristen L. Miller, Eun-Deok Kim, Takashi Miura, Keiko U. Torii
DEVELOPMENTAL CELL
(2018)
Article
Cell Biology
Tomohiro Miyai, Junichiro Takano, Takaho A. Endo, Eiryo Kawakami, Yasutoshi Agata, Yasutaka Motomura, Masato Kubo, Yukie Kashima, Yutaka Suzuki, Hiroshi Kawamoto, Tomokatsu Ikawa
GENES & DEVELOPMENT
(2018)
Article
Immunology
Mari Tenno, Satoshi Kojo, Divine-Fondzenyuy Lawir, Isabell Hess, Katsuyuki Shiroguchi, Takashi Ebihara, Takaho A. Endo, Sawako Muroi, Rumi Satoh, Hiroshi Kawamoto, Thomas Boehm, Ichiro Taniuchi
JOURNAL OF EXPERIMENTAL MEDICINE
(2018)
Article
Allergy
Norimasa Tamehiro, Kyoko Nishida, Yu Sugita, Kunihiro Hayakawa, Hiroyo Oda, Takeshi Nitta, Miwa Nakano, Akiko Nishioka, Reiko Yanobu-Takanashi, Motohito Goto, Tadashi Okamura, Reiko Adachi, Kazunari Kondo, Akimichi Morita, Harumi Suzuki
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2019)
Article
Developmental Biology
Hirofumi Nishizono, Mohamed Darwish, Takaho A. Endo, Kyosuke Uno, Hiroyuki Abe, Ryohei Yasuda
Article
Immunology
Masayuki Kitajima, Masato Kubo, Steven F. Ziegler, Harumi Suzuki
JOURNAL OF IMMUNOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Yuji Kurihara, Toshiyuki Takai, Kohtaro Takei
JOURNAL OF NEUROCHEMISTRY
(2020)
Article
Cell Biology
Satomi Takahashi, Ikuo Nobuhisa, Kiyoka Saito, Melig Gerel, Ayumi Itabashi, Kaho Harada, Mitsujiro Osawa, Takaho A. Endo, Atsushi Iwama, Tetsuya Taga
Article
Multidisciplinary Sciences
Yasuhide Ohinata, Takaho A. Endo, Hiroki Sugishita, Takashi Watanabe, Yusuke Iizuka, Yurie Kawamoto, Atsunori Saraya, Mami Kumon, Yoko Koseki, Takashi Kondo, Osamu Ohara, Haruhiko Koseki
Summary: This study reports the derivation of primitive endoderm stem cells (PrESCs) in mice, which recapitulate the developmental potential of primitive endoderm. PrESCs can efficiently incorporate into the embryo and interact with other stem cells, generating descendants with yolk sac-like structures.
Article
Biology
Stacey A. Vincent, Jong-Myong Kim, Imma Perez-Salamo, Taiko Kim To, Chieko Torii, Junko Ishida, Maho Tanaka, Takaho A. Endo, Prajwal Bhat, Paul F. Devlin, Motoaki Seki, Alessandra Devoto
Summary: The study shows that jasmonates and HDA6 have overlapping functions in regulating plant development and response to stress at the level of histone modifications. Jasmonates and HDA6 modulate histone modifications in different ways to regulate genetic variability and enable adaptation to environmental challenges.
Article
Immunology
Fumika Itagaki, Keita Nakatsuka, Haruka Sakai, Shota Endo, Mei-Tzu Su, Toshiyuki Takai
Summary: Natural killer (NK) cells play important roles in innate immunity and anti-tumor responses, while their activity is regulated by inhibitory receptors. The inhibitory receptor ILT3/LILRB4, found on activated NK cells, is hypothesized to bind fibronectin on target cells along with integrins and deliver an inhibitory signal. This study suggests that NK cell cytotoxicity is negatively regulated through the sensing of fibronectin by LILRB4/gp49B on target cells, shedding light on their unexpected role in attenuating NK cell cytotoxicity in the tumor microenvironment.
INTERNATIONAL IMMUNOLOGY
(2023)
Article
Immunology
Mei-Tzu Su, Karin Ono, Dai Kezuka, Shotaro Miyamoto, Yu Mori, Toshiyuki Takai
Summary: The interaction between LILRB4/gp49B and Fibronectin plays a crucial role in osteoclastogenesis, negatively regulating the signaling pathway induced by RANKL and inhibiting osteoclast formation.
INTERNATIONAL IMMUNOLOGY
(2023)
Meeting Abstract
Immunology
M. Kitajima, S. Ziegler, H. Suzuki
EUROPEAN JOURNAL OF IMMUNOLOGY
(2019)