Article
Medicine, Research & Experimental
Yuanyang Wang, Cheng Qin, Bangbo Zhao, Zeru Li, Tianyu Li, Xiaoying Yang, Yutong Zhao, Weibin Wang
Summary: This study found that EGR1 is highly expressed in pancreatic cancer and is associated with prognosis and cancer metastasis. EGR1 promotes migration and invasion ability of pancreatic cancer cells and is correlated with the epithelial-mesenchymal transition process. The study also revealed that EGR1 activates the SNAI2 gene through interaction with p300/CBP. In vivo experiments confirmed that EGR1 promotes liver metastasis of pancreatic cancer. Therefore, blocking the expression of EGR1 could be a new anticancer strategy for pancreatic cancer.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Kee-Beom Kim, Ashish Kabra, Dong-Wook Kim, Yongming Xue, Yuanjian Huang, Pei-Chi Hou, Yunpeng Zhou, Leilani J. Miranda, Jae-Il Park, Xiaobing Shi, Timothy P. Bender, John H. Bushweller, Kwon-Sik Park
Summary: EP300, an important transcription coactivator in proliferation and differentiation, is frequently mutated in various cancer types. This study found that EP300 mutants without acetyltransferase domain accelerate tumor development in small cell lung cancer (SCLC) mouse models, while complete EP300 knockout suppresses SCLC development and proliferation. The kinase inducible domain-interacting (KIX) domain of EP300, specifically its interaction with transcription factors including MYB, was identified as the determinant of protumorigenic activity. Inhibition of KIX-mediated interactions inhibits SCLC development and cell growth.
Review
Medicine, Research & Experimental
Qingjuan Chen, Binhui Yang, Xiaochen Liu, Xu D. Zhang, Lirong Zhang, Tao Liu
Summary: CBP/p300, critical drivers of oncogenesis, promote tumorigenesis and have been shown to be over-expressed in cancer cells; their inhibitors and degraders are considered promising anticancer agents that reduce H3K27ac, regulate oncogene transcription, induce cancer cell death and activate immune response.
Article
Multidisciplinary Sciences
Jin Wu, Yingying Han, Hao Xu, Hongyang Sun, Rui Wang, Haigang Ren, Guanghui Wang
Summary: This study investigates the role of chaperone-mediated autophagy (CMA) in neuroinflammation and its impact on microglia activation and neuronal damage. The researchers found that CMA activation can inhibit microglial activation and inflammation through the p300-associated NF-kappa B signaling pathway. Additionally, they demonstrated that CMA dysfunction worsens microglial activation and inflammation. These findings provide insight into the mechanistic link between CMA and neuroinflammation.
Article
Neurosciences
Michal Lipinski, Sergio Ninerola, Miguel Fuentes-Ramos, Luis M. Valor, Beatriz del Blanco, Jose P. Lopez-Atalaya, Angel Barco
Summary: Environmental factors and life experiences can affect brain circuits, triggering adaptive changes. Epigenetic regulators play a crucial role in this neuroadaptation. The elimination of CBP reduces the expression and chromatin acetylation of plasticity genes, weakens activity-driven transcription, and causes memory deficits.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Fabienne Bejjani, Claire Tolza, Mathias Boulanger, Damien Downes, Raphael Romero, Muhammad Ahmad Maqbool, Amal Zine El Aabidine, Jean-Christophe Andrau, Sophie Lebre, Laurent Brehelin, Hughes Parrinello, Marine Rohmer, Tony Kaoma, Laurent Vallar, Jim R. Hughes, Kazem Zibara, Charles-Henri Lecellier, Marc Piechaczyk, Isabelle Jariel-Encontre
Summary: The dimeric transcription factors AP-1, composed of Fos and Jun family proteins, play a key role in gene regulation. The overexpression of the Fos family protein Fra-1 in triple negative breast cancers contributes to tumor aggressiveness, while its actions in controlling transcription remain complex and involve a wide range of biological processes.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Microbiology
Wesley Kendle, Kimson Hoang, Erica Korleski, Amanda R. Panfil, Nicholas Polakowski, Isabelle Lemasson
Summary: Infection with human T-cell leukemia virus type 1 (HTLV-1) can cause various pathological effects. HTLV-1 predominantly infects CD4(+) T-cells and spreads through cell-to-cell contact. HBZ, a viral protein, enhances HTLV-1 infection by activating ICAM1 and MYOF genes.
Article
Multidisciplinary Sciences
Archana Bommi-Reddy, Sungmi Park-Chouinard, David N. Mayhew, Esteban Terzo, Aparna Hingway, Michael J. Steinbaugh, Jonathan E. Wilson, Robert J. Sims, Andrew R. Conery
Summary: This study demonstrates that the acetyltransferase activity of coactivator paralogs CREBBP/EP300 is a promising therapeutic target in ER+ breast cancer. It acts orthogonal to directly targeting ER and inhibits ER-dependent transcription by targeting enhancers defined by the pioneer transcription factor FOXA1.
Article
Medicine, Research & Experimental
Guizhen Zhao, Yang Zhao, Haocheng Lu, Ziyi Chang, Hongyu Liu, Huilun Wang, Wenying Liang, Yuhao Liu, Tianqing Zhu, Oren Rom, Yanhong Guo, Lin Chang, Bo Yang, Minerva T. Garcia-Barrio, Jiandie D. Lin, Y. Eugene Chen, Jifeng Zhang
Summary: The study demonstrates that BAF60c plays a crucial role in preventing and treating abdominal aortic aneurysm (AAA). It maintains the contractile phenotype of vascular smooth muscle cells (VSMCs), suppresses inflammation, and prevents apoptosis to maintain VSMC homeostasis.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biochemistry & Molecular Biology
Fabienne Bejjani, Emilie Evanno, Samantha Mahfoud, Claire Tolza, Kazem Zibara, Marc Piechaczyk, Isabelle Jariel-Encontre
Summary: This study reveals that the transcription factor Fra-1 down-regulates the expression of the TGFB2 gene by decreasing the formation of its transcription-initiating form. Complex long-range chromatin interactions involving multiple heterogeneous Fra-1-bound transcriptional enhancers are involved in this process. The transcriptional output of the TGFB2 gene depends on a balance between the positive and negative effects of Fra-1 at these enhancers.
CELL AND BIOSCIENCE
(2023)
Article
Immunology
Lairong Wang, Yan Wang, Meijuan Meng, Nana Ma, Guozhen Wei, Ran Huo, Guangjun Chang, Xiangzhen Shen
Summary: High-concentrate diet can induce subacute ruminal acidosis (SARA) and mastitis in dairy cows. In this study, cows were fed low-concentrate or high-concentrate diets, and the results showed that high-concentrate diet reduced ruminal pH and increased lactate concentration in mammary gland and plasma. Furthermore, high-concentrate diet also caused inflammatory responses and activated the TLR4/NF-kappa B signaling pathway.
MICROBIAL PATHOGENESIS
(2023)
Article
Oncology
Tao Zhang, Bofang Wang, Baohong Gu, Fei Su, Lin Xiang, Le Liu, Xuemei Li, Xueyan Wang, Lei Gao, Hao Chen
Summary: This research systematically analyzed the molecular alterations and clinical relevance of histone acetyltransferase (HAT) and histone deacetylase (HDAC) genes in five types of digestive cancers. It found recurrent mutations and copy number variations in acetylation-associated genes, and identified their correlation with cancer hallmark-related pathways. The expression pattern of these genes stratified patients' clinical benefit in hepatocellular carcinoma and pancreatic cancer.
JOURNAL OF ONCOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Stephen T. Joy, Matthew J. Henley, Samantha N. De Salle, Matthew S. Beyersdorf, Isaac W. Vock, Allison J. L. Huldin, Anna K. Mapp
Summary: MybLL-tide is a picomolar dual-site inhibitor of the Myb-CBP/p300 KIX interaction, showing high affinity and selectivity, effectively inhibiting key genes in AML cells.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Review
Oncology
Aaron R. Waddell, Haojie Huang, Daiqing Liao
Summary: CBP and p300 are paralogous lysine acetyltransferases that play critical roles in regulating transcription factors in cancer signaling pathways. They have been established as important regulators of nuclear hormone signaling, such as androgen receptor (AR) and estrogen receptor (ER), which are associated with tumor growth in hormone-dependent prostate and breast cancers. Inhibitors targeting CBP and p300 show potential as a novel therapeutic strategy for prostate and breast cancers by blocking AR and ER transactivation activity.
Article
Multidisciplinary Sciences
Shaochen You, Michael J. Bollong
Summary: ChREBP, a central regulator of metabolism, senses and responds to dietary glucose levels by stimulating the transcription of glycolytic and lipogenic enzymes. A recent pharmacological screen identified novel inhibitors of ChREBP-driven transcription, providing a toolkit to investigate ChREBP activation and potential therapeutic approaches for metabolic diseases.
Review
Immunology
Koji Onomoto, Kazuhide Onoguchi, Mitsutoshi Yoneyama
Summary: RLRs are RNA sensor molecules that play essential roles in innate antiviral immunity by inducing downstream signaling via interactions with various host and viral factors. The signaling mediated by RLRs is regulated by interactions with endogenous RNAs and host proteins, and deregulation can lead to autoimmune and autoinflammatory disorders.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Nanoscience & Nanotechnology
Noriyuki Kodera, Daisuke Noshiro, Sujit K. Dora, Tetsuya Mori, Johnny Habchi, David Blocquel, Antoine Gruet, Marion Dosnon, Edoardo Salladini, Christophe Bignon, Yuko Fujioka, Takashi Oda, Nobuo N. Noda, Mamoru Sato, Marina Lotti, Mineyuki Mizuguchi, Sonia Longhi, Toshio Ando
Summary: High-speed atomic force microscopy imaging can provide a semiquantitative, realistic description of the dynamic structure of intrinsically disordered proteins, which dynamically sample a multitude of conformational states, making their structural analysis difficult.
NATURE NANOTECHNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
William J. Valentine, Keisuke Yanagida, Hiroki Kawana, Nozomu Kono, Nobuo N. Noda, Junken Aoki, Hideo Shindou
Summary: The diversity of glycerophospholipid species in cellular membranes is immense and is influenced by the enzymes GPATs, LPLATs, and phospholipase A(1/2)s. In mammals, these enzymes play essential roles in physiology and disease processes.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Yushi Hayashi, Hidenori Suzuki, Wataru Nakajima, Ikuno Uehara, Atsuko Tanimura, Toshiki Himeda, Satoshi Koike, Tatsuya Katsuno, Shin-ichiro Kitajiri, Naoto Koyanagi, Yasushi Kawaguchi, Koji Onomoto, Hiroki Kato, Mitsutoshi Yoneyama, Takashi Fujita, Nobuyuki Tanaka
Summary: The research revealed that viral infection is a major cause of sensorineural hearing loss, and the mechanism of virus-induced hair cell death in the cochlear sensory epithelium was explored. Corticosteroids were found to inhibit virus-induced hair cell death, suggesting a potential target for preventing virus-induced SHL.
Article
Biochemistry & Molecular Biology
Haruka Chino, Akinori Yamasaki, Koji L. Ode, Hiroki R. Ueda, Nobuo N. Noda, Noboru Mizushima
Summary: This study reveals the critical role of LIR phosphorylation in the interaction, localization, and initiation of autophagy of the ER-phagy receptor TEX264 with ATG8. Structural analysis shows that phosphorylation increases binding affinity by generating multiple hydrogen bonds with ATG8, which cannot be mimicked by acidic residues. This finding highlights the importance of LIR phosphorylation in LIR-ATG8 interactions.
Article
Cell Biology
Takuo Osawa, Kazuaki Matoba, Nobuo N. Noda
Summary: This article summarizes the recent advances in the lipid transport activities of autophagy-related proteins and their collaboration mechanisms during autophagosome formation.
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Yuji Kubota, Yuko Fujioka, Ashwini Patil, Yusuke Takagi, Daisuke Matsubara, Masatomi Iijima, Isao Momose, Ryosuke Naka, Kenta Nakai, Nobuo N. Noda, Mutsuhiro Takekawa
Summary: This study reveals the mutant structure of MEK1 and qualitative differences in biological properties between cancer- and RASopathy-associated mutants, providing insights into the pathophysiology, diagnosis, and treatment of these diseases.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Sang-Won Park, Pureum Jeon, Akinori Yamasaki, Hye Eun Lee, Haneul Choi, Ji Young Mun, Yong-Woo Jun, Ju-Hui Park, Seung-Hwan Lee, Soo-Kyeong Lee, You-Kyung Lee, Hyun Kyu Song, Michael Lazarou, Dong-Hyong Cho, Masaaki Komatsu, Nobuo N. Noda, Deok-Jin Jang, Jin-A Lee
Summary: This study identified the selective interactions of various membrane-anchored mATG8 proteins in mammals and developed tools to regulate the autophagy of disease-related protein aggregates. This has significant implications for understanding the functional roles of mATG8 proteins on autophagic membranes in autophagy research.
Article
Chemistry, Multidisciplinary
Jin Cui, Yuta Ogasawara, Ikuko Kurata, Kazuaki Matoba, Yuko Fujioka, Nobuo N. Noda, Masakatsu Shibasaki, Takumi Watanabe
Summary: The study demonstrates that a stapled peptide derived from ATG16L1 exhibits potent binding affinity to ATG5, strong resistance to proteolysis, and significant autophagy inhibition activities in cells.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Review
Oncology
Yutaro Hama, Yuta Ogasawara, Nobuo N. Noda
Summary: Autophagy is a cellular process that degrades biomolecules and organelles, contributing to cellular homeostasis. Its roles in cancer are complex, acting as either a promoter or suppressor depending on the cancer stage and type. This review summarizes the basic mechanisms of autophagy and discusses its complicated roles in cancer. Additionally, it provides an overview of clinical trials on autophagy inhibitors for cancer and the development of more specific inhibitors for future clinical application.
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.
Editorial Material
Cell Biology
Tomoyuki Fukuda, Kentaro Furukawa, Tatsuro Maruyama, Nobuo N. Noda, Tomotake Kanki
Summary: Mitophagy is a selective form of autophagy that targets dysfunctional or superfluous mitochondria for degradation. Our recent study has identified Atg44 as a mitochondrial fission factor that generates mitochondrial fragments suitable for phagophore engulfment. We propose the term mitofissin to refer to Atg44 and its homologous proteins that might participate in diverse cellular processes.
Review
Biochemistry & Molecular Biology
Nobuo N. Noda
Summary: Autophagy is a conserved intracellular degradation system that involves the sequestration of degradation targets into autophagosomes. Autophagosome formation and cargo selectivity rely on core Atg proteins and cargo receptors, respectively. This review covers the 30-year history of structural studies on core Atg proteins and cargo receptors and discusses the molecular mechanisms of autophagosome formation and selective autophagy.
Article
Cell Biology
Kanae Hitomi, Tetsuya Kotani, Nobuo N. Noda, Yayoi Kimura, Hitoshi Nakatogawa
Summary: Hitomi et al. reveal that the phosphatidylinositol 3-kinase complex I is recruited to the autophagosome precursor via interactions with Vac8, Atg1 complex, and Atg9. These interactions cooperate to target the phosphatidylinositol 3-kinase complex I to the pre-autophagosomal structure and provide a molecular basis for its localization during autophagosome biogenesis.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Ryosuke Ishimura, Sota Ito, Gaoxin Mao, Satoko Komatsu-Hirota, Toshifumi Inada, Nobuo N. Noda, Masaaki Komatsu
Summary: Research has shown that UFM1 plays a role in processes such as endoplasmic reticulum-associated protein degradation, ribosome-associated protein quality control, and ER-phagy, and the UFM1 E3 complex is involved in both ufmylation and ER-RQC.
