Review
Pharmacology & Pharmacy
Daniela Maria Tanase, Alina Georgiana Apostol, Claudia Florida Costea, Claudia Cristina Tarniceriu, Ionut Tudorancea, Minela Aida Maranduca, Mariana Floria, Ionela Lacramioara Serban
Summary: Arterial hypertension is a prevalent disease characterized by increased incidence and heterogeneous pathophysiology. Oxidative stress plays an important role in its development, with excessive levels causing vascular cell damage and promoting hypertension. Transcription factors such as Nrf2 mediate antioxidant response pathways and provide protection.
Article
Biochemistry & Molecular Biology
Fan Kou, Lei Wu, Yu Zheng, Yeran Yi, Zhenyu Ji, Ziqi Huang, Shiwei Guo, Lili Yang
Summary: This study reveals the critical role of HMGB1 in glycolysis and metastasis in LUAD, by attenuating H3K9ace and H3K27ace through physical interaction with SET and HAT1.
Article
Biochemistry & Molecular Biology
Fan Kou, Lei Wu, Yu Zheng, Yeran Yi, Zhenyu Ji, Ziqi Huang, Shiwei Guo, Lili Yang
Summary: This study found that in lung adenocarcinoma, the overexpression of HMGB1 is associated with tumor grade and poor survival. HMGB1 interacts physically with SET and HAT1 to suppress H3K9ace and H3K27ace acetylation, promoting glycolysis and metastasis.
Article
Plant Sciences
Peng Feng, Xiaohuan Sun, Xiaodong Liu, Yuqiu Li, Qi Sun, Haoran Lu, Minglong Li, Xiaodong Ding, Yingshan Dong
Summary: The study found that the interaction between GsMYST1 and GsSnRK1 can regulate the expression of the COR15B gene through acetylation. Additionally, it was demonstrated that salt stress can activate GsSnRK1, which subsequently phosphorylates GsMYST1 to enhance its acetyltransferase activity, potentially promoting target gene expression through epigenetics.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Biology
Alicia Tapias, David Lazaro, Bo-Kun Yin, Seyed Mohammad Mahdi Rasa, Anna Krepelova, Erika Kelmer Sacramento, Paulius Grigaravicius, Philipp Koch, Joanna Kirkpatrick, Alessandro Ori, Francesco Neri, Zhao-Qi Wang
Summary: The study reveals the importance of TRRAP for neuroprotection and the network connecting TRRAP, HAT, and SP1 in regulating microtubule dynamics.
Article
Fisheries
Yun Wang, Yafei Duan, Jianhua Huang, Jun Wang, Chuanpeng Zhou, Shigui Jiang, Heizhao Lin, Zhe Zhang
Summary: PmNrf2, a member of CNC-bZIP transcription factor family, is constitutively expressed in various tissues of shrimp and responds to bacterial challenge. Knockdown of PmNrf2 results in decreased expression of PmGPx gene, indicating its role in regulating the transcription of antioxidant enzyme genes in shrimp.
FISH & SHELLFISH IMMUNOLOGY
(2021)
Review
Pharmacology & Pharmacy
Shunhao Zhang, Sining Duan, Zhuojun Xie, Wanlin Bao, Bo Xu, Wenbin Yang, Lingyun Zhou
Summary: The NRF2/KEAP1 signaling pathway plays a key role in cellular physiology by protecting cells from stress conditions. However, recent studies have shown that this pathway may have oncogenic effects and contribute to therapy resistance. This article investigates the role of epigenetic modifications in regulating the NRF2/KEAP1 signaling pathway and its impact on cancer development, and explores the potential of targeting epigenetic changes as therapeutic targets.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Laura Janko, Emese Toth, Miklos Laczik, Boglarka Rauch, Eszter Janka, Balint L. Balint, Peter Bai
Summary: PARP2 plays a role in DNA repair and has regulatory functions in mitochondrial and lipid metabolism. It is also involved in the adverse effects of pharmacological PARP inhibitors. Silencing of PARP2 affects the subcellular localization of NRF2, a regulator of cellular antioxidant defense, and leads to changes in the expression of genes encoding proteins with antioxidant function.
SCIENTIFIC REPORTS
(2023)
Review
Biochemistry & Molecular Biology
Pin Zhao, Samiullah Malik
Summary: This review describes how phosphorylation affects the transcription activity and other functions of DNA/histone modifying enzymes. Although the phosphorylated sites of these enzymes have been classified and partially explained, further research is still needed to determine their relationship with disease-associated transcriptional regulation.
CELL AND BIOSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Anagh Ray, Preeti Khan, Ronita Nag Chaudhuri
Summary: The study highlights the importance of lysine acetylation in maintaining chromatin structure and function, specifically focusing on the role of H4K16 acetylation in regulating the expression of constitutive genes. Deacetylation of H4K16 is associated with hypoacetylation of H4K12 and H3K9, along with hyperacetylation of H3K56, creating a chromatin landscape conducive for transcription of constitutive genes.
Article
Oncology
Jared Sivinski, Donna D. Zhang, Eli Chapman
Summary: NRF2 is a crucial transcription factor that regulates redox homeostasis. While being activated can protect normal cells, abnormal upregulation of NRF2 may facilitate the growth and spread of cancer cells. Researchers are therefore interested in discovering both NRF2 activators and inhibitors to better understand and control its dual role in health and disease.
SEMINARS IN CANCER BIOLOGY
(2021)
Article
Oncology
Xiaohui Pan, Wenxin Zhang, Longsheng Wang, Hongjie Guo, Mingming Zheng, Honghai Wu, Qinjie Weng, Qiaojun He, Ling Ding, Bo Yang
Summary: Recent studies have shown that Krupple-like factor 12 (KLF12) plays a crucial role in cancer-associated processes in non-small cell lung cancer (NSCLC), including proliferation, apoptosis, and metastasis. KLF12 is positively correlated with programmed death-ligand 1 (PD-L1) expression and can bind to the CACCC motif of the PD-L1 promoter to promote transcription. Knockout of KLF12 inhibits tumor growth and enhances infiltration of CD8(+) T cells in immunocompetent mice.
MOLECULAR ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Qian Shen, Ji Fang, Hengjiang Guo, Xue Su, Bingbing Zhu, Xingmei Yao, Yunman Wang, Aili Cao, Hao Wang, Li Wang
Summary: Defective antioxidant system and mitochondrial dysfunction contribute to the pathogenesis and progression of diabetic kidney disease (DKD). The activation of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated signaling, which is the central defensive mechanism against oxidative stress, has shown potential as a therapeutic strategy. Astragaloside IV (AS-IV), an active ingredient from Huangqi decoction (HQD), was found to promote Nrf2 escape from Keap1-Nrf2 interaction. AS-IV improved mitochondrial function, resistance to oxidative stress-induced diabetic kidney injury and podocyte apoptosis, and the process is closely associated with activation of Nrf2-ARE/TFAM signaling.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Multidisciplinary Sciences
Daniel Schator, Sonia Mondino, Jeremy Berthelet, Cristina Di Silvestre, Mathilde Ben Assaya, Christophe Rusniok, Fernando Rodrigues-Lima, Annemarie Wehenkel, Carmen Buchrieser, Monica Rolando
Summary: Legionella pneumophilia secretes more than 300 effectors, including RomA and LphD, via a type IV secretion system. RomA methylates histone H3 at K14 to counteract host immune responses, while LphD deacetylates H3K14 to work synergistically with RomA. The two effectors target host chromatin and bind the HBO1 histone acetyltransferase complex to regulate histone modifications.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, Research & Experimental
Jian Lu, Xue Qi Li, Pei Pei Chen, Jia Xiu Zhang, Liang Liu, Gui Hua Wang, Xiao Qi Liu, Ting Ting Jiang, Meng Ying Wang, Wen Tao Liu, Xiong Zhong Ruan, Kun Ling Ma
Summary: This study found that ACSS2 activation promoted podocyte injury in diabetic nephropathy by inhibiting autophagy through the raptor/mTORC1 pathway. Inhibition of ACSS2 improved autophagy and alleviated podocyte injury.
Review
Biochemistry & Molecular Biology
Hironari Nishizawa, Mie Yamanaka, Kazuhiko Igarashi
Summary: Ferroptosis is a form of cell death triggered by intracellular peroxidation of cell membrane phospholipids. It is regulated by transcription factors NRF2 and BACH1, which control various pathways and processes involved in ferroptosis.
Article
Biochemistry & Molecular Biology
Kei Segawa, Kazuhiko Igarashi, Kazutaka Murayama
Summary: The function of the transcription factor BACH1 is regulated by heme binding to multiple Cys-Pro (CP) motifs within its intrinsically disordered regions. The individual CP motifs contribute to the regulation of BACH1 activity by accepting heme in different coordination manners and their spatial locations are important for their individual functions. The presence of multiple CP motifs with distinct roles ensures the multifaceted, strict regulation of BACH1 by heme.
Article
Hematology
Masatoshi Ikeda, Hiroki Kato, Hiroki Shima, Mitsuyo Matsumoto, Eijiro Furukawa, Yan Yan, Ruiqi Liao, Jian Xu, Akihiko Muto, Tohru Fujiwara, Hideo Harigae, Emery H. Bresnick, Kazuhiko Igarashi
Summary: Iron deficiency promotes mitochondrial retention in red blood cells, while heme promotes mitochondrial clearance and erythroblast differentiation. The transcription factor GATA1 regulates autophagy and induces mitophagy through a heme-dependent mechanism. This mechanism provides a molecular framework for understanding this important cell biological process.
EXPERIMENTAL HEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Md Morshedul Alam, Akihiro Kishino, Eunkyu Sung, Hiroki Sekine, Takaaki Abe, Shohei Murakami, Takaaki Akaike, Hozumi Motohashi
Summary: NRF2 increases intracellular persulfides levels by upregulating the expression of cystine transporter xCT, thereby enhancing mitochondrial function.
Article
Biochemistry & Molecular Biology
Ryo Ikeda, Daisuke Noshiro, Hideaki Morishita, Shuhei Takada, Shun Kageyama, Yuko Fujioka, Tomoko Funakoshi, Satoko Komatsu-Hirota, Ritsuko Arai, Elena Ryzhii, Manabu Abe, Tomoaki Koga, Hozumi Motohashi, Mitsuyoshi Nakao, Kenji Sakimura, Arata Horii, Satoshi Waguri, Yoshinobu Ichimura, Nobuo N. Noda, Masaaki Komatsu
Summary: ULK1 is a kinase responsible for the phosphorylation of p62, which activates NRF2. p62(S351E/+) mice, with phosphorylation-mimicking mutation, exhibit NRF2 hyperactivation and growth retardation.
Article
Biochemistry & Molecular Biology
Qamarul Hafiz Zainol Abidin, Tomoaki Ida, Masanobu Morita, Tetsuro Matsunaga, Akira Nishimura, Minkyung Jung, Naim Hassan, Tsuyoshi Takata, Isao Ishii, Warren Kruger, Rui Wang, Hozumi Motohashi, Masato Tsutsui, Takaaki Akaike
Summary: Reactive sulfur species, such as cysteine hydropersulfide and glutathione persulfide, are produced abundantly in both prokaryotes and eukaryotes, including mammals. Cysteinyl-tRNA synthetase (CARS) has been identified as a new cysteine persulfide synthase (CPERS) responsible for the production of most reactive persulfides. However, the contribution of other enzymes, such as 3-mercaptopyruvate sulfurtransferase (3-MST), cystathionine beta-synthase (CBS), and cystathionine gamma-lyase (CSE), to reactive persulfide production is still debated. In this study, the authors used sulfur metabolome analysis to demonstrate that 3-MST, CBS, and CSE are not major sources of reactive persulfides in mammals, and CARS/CPERS is the principal enzyme involved.
Article
Hematology
Koki Nagai, Tetsuya Niihori, Akihiko Muto, Yoshikazu Hayashi, Taiki Abe, Kazuhiko Igarashi, Yoko Aoki
Summary: Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT) is an inherited bone marrow failure syndrome caused by missense mutations in the MECOM gene. Knockin mice harboring RUSAT-associated MECOM mutations recapitulate the bone marrow dysfunction observed in RUSAT patients.
Article
Multidisciplinary Sciences
Tetsuro Matsunaga, Hirohito Sano, Katsuya Takita, Masanobu Morita, Shun Yamanaka, Tomohiro Ichikawa, Tadahisa Numakura, Tomoaki Ida, Minkyung Jung, Seiryo Ogata, Sunghyeon Yoon, Naoya Fujino, Yorihiko Kyogoku, Yusaku Sasaki, Akira Koarai, Tsutomu Tamada, Atsuhiko Toyama, Takakazu Nakabayashi, Lisa Kageyama, Shigeru Kyuwa, Kenji Inaba, Satoshi Watanabe, Peter Nagy, Tomohiro Sawa, Hiroyuki Oshiumi, Masakazu Ichinose, Mitsuhiro Yamada, Hisatoshi Sugiura, Fan-Yan Wei, Hozumi Motohashi, Takaaki Akaike
Summary: Supersulphides have diverse physiological functions and their synthesis is mediated by CARS2. They play a protective role in viral airway infections, aged lungs, and chronic lung diseases. Supersulphides can mitigate lung pathology and lethal effects in animal models, highlighting their potential as a therapeutic target.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Haruna Takeda, Shohei Murakami, Zun Liu, Tomohiro Sawa, Masatomo Takahashi, Yoshihiro Izumi, Takeshi Bamba, Hideyo Sato, Takaaki Akaike, Hiroki Sekine, Hozumi Motohashi
Summary: The excessive inflammatory response of macrophages is regulated by the metabolic alteration involving cysteine and its related metabolites. Activation of the cystine transporter xCT increases cysteine uptake by macrophages and contributes to the production of supersulfides, creating a negative feedback loop to limit excessive inflammation. Understanding the finely tuned regulation of macrophage inflammatory response by sulfur metabolism is important for disease pathogenesis and potential therapeutic strategies.
Article
Multidisciplinary Sciences
Shingo Kasamatsu, Akira Nishimura, Md. Morshedul Alam, Masanobu Morita, Kakeru Shimoda, Tetsuro Matsunaga, Minkyung Jung, Seiryo Ogata, Uladzimir Barayeu, Tomoaki Ida, Motohiro Nishida, Akiyuki Nishimura, Hozumi Motohashi, Takaaki Akaike
Summary: Research has found that abundant formation of endogenous supersulfides catalyzes S-nitrosoglutathione (GSNO) metabolism by utilizing alcohol dehydrogenase 5 (ADH5), which serves as GSNO reductase (GSNOR) and formaldehyde dehydrogenase (FDH). The C174S mutation in ADH5 significantly reduces supersulfidation and GSNOR activity but spares FDH activity. ADH5 supersulfides play a substantial role in GSNO metabolism by mediating electron transfer from aldehydes.
Review
Immunology
Kyoko Ochiai, Kazuhiko Igarashi
Summary: BACH2 is a transcriptional repressor that regulates gene expression in B cells, promoting antibody class switch and affinity maturation while repressing plasma-cell differentiation. Recent studies suggest that BACH2 may have diverse functions, including gene activation. Understanding these new functions could provide insights into preventing human immune deficiencies.
INTERNATIONAL IMMUNOLOGY
(2023)
Meeting Abstract
Hematology
Koya Ono, Tohru Fujiwara, Hiroki Shima, Hironari Nishizawa, Chie Suzuki, Noriyuki Takahashi, Hiroki Kato, Koichi Onodera, Satoshi Ichikawa, Noriko Fukuhara, Yasushi Onishi, Hisayuki Yokoyama, Yukio Nakamura, Kazuhiko Igarashi, Hideo Harigae
Meeting Abstract
Oncology
Kazuhiko Igarashi, Hironari Nishizawa, Mitsuyo Matsumoto