Article
Biochemistry & Molecular Biology
Xue Zhong, Huiwen Deng, Min Long, Honglu Yin, Qiu Zhong, Shilong Zheng, Tao Gong, Ling He, Guangdi Wang, Qiu Sun
Summary: Berberine was discovered as a potent p300/CBP HAT inhibitor and showed inhibition of tumor growth. Novel analog 5d, derived from berberine, demonstrated high selectivity towards p300/CBP HAT and effectively suppressed tumor growth in animal models. Furthermore, liposomes-encapsulated 5d showed increased inhibition of tumor growth with good absorption properties in vivo.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Hong Ding, Yuan Pei, Yuanqing Li, Wen Xu, Lianghe Mei, Zeng Hou, Yiman Guang, Liyuan Cao, Peizhuo Li, Haijing Cao, Jinlei Bian, Kaixian Chen, Cheng Luo, Bing Zhou, Ting Zhang, Zhiyu Li, Yaxi Yang
Summary: This study modified the p300/CBP HAT domain inhibitor and obtained a highly active small molecule that showed significant anti-proliferation activity on ovarian cancer cells. The discovery provides a novel idea for the application of epigenetic inhibitors in the treatment of ovarian cancer.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Zhiqin Ji, Richard F. Clark, Vikram Bhat, T. Matthew Hansen, Loren M. Lasko, Kenneth D. Bromberg, Vlasios Manaves, Mikkel Algire, Ruth Martin, Wei Qiu, Maricel Torrent, Clarissa G. Jakob, Hong Liu, Philip A. Cole, Ronen Marmorstein, Edward A. Kesicki, Albert Lai, Michael R. Michaelides
Summary: p300 and CBP play essential roles in cellular processes and dysregulation of their histone acetyltransferase activity is linked to various human diseases. The novel drug-like compound 21 is a selective orally bioavailable inhibitor of p300/CBP histone acetyltransferase, more potent than A-485 and lacking off-target inhibition of dopamine and serotonin transporters.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Medicinal
Shenyou Nie, Fangrui Wu, Jingyu Wu, Xin Li, Chao Zhou, Yuan Yao, Yongcheng Song
Summary: Acetylation of histone lysine residues by p300 and CBP plays important roles in gene regulation. Compound 29 is a potential inhibitor of p300 HAT with activity against cancer cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Hyo-Jin Kim, Jangho Lee, Min-Yu Chung, Soo Hyun Park, Jae Ho Park, Hyo-Kyoung Choi, Jin-Taek Hwang
Summary: Tamarixetin (TX) derived from natural products is a potent antilipogenic agent that reduces lipid accumulation and inhibits the expression and activity of p300/CBP-associated factor (pCAF), thereby decreasing lipogenesis-related gene expression.
JOURNAL OF MEDICINAL FOOD
(2022)
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.
Article
Pharmacology & Pharmacy
Yoichi Sunagawa, Kiyotaka Shimizu, Ayumi Katayama, Masafumi Funamoto, Kana Shimizu, Sari Nurmila, Satoshi Shimizu, Yusuke Miyazaki, Yasufumi Katanasaka, Koji Hasegawa, Tatsuya Morimoto
Summary: The study investigated the potential effects of metformin on cardiac hypertrophy by inhibiting p300-mediated acetylation of histone-H3K9 and hypertrophic responses in cardiomyocytes. Metformin was shown to suppress PE-induced and p300-mediated hypertrophic responses, suggesting its potential therapeutic use in patients with diabetes and heart failure.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2021)
Article
Cell Biology
Linlin Zhang, Chunxiang Sheng, Feiye Zhou, Kecheng Zhu, Shushu Wang, Qianqian Liu, Miaomiao Yuan, Zhaoqian Xu, Yun Liu, Jieli Lu, Jianmin Liu, Libin Zhou, Xiao Wang
Summary: In this study, it was found that the HAT activity of CBP/p300 plays a dominant role in maintaining the identity of insulin-secreting β cells by regulating the expression of functional genes through transcriptional networks.
CELL DEATH & DISEASE
(2021)
Article
Chemistry, Medicinal
Anthony Mastracchio, Chunqiu Lai, Enrico Digiammarino, Damien B. Ready, Loren M. Lasko, Kenneth D. Bromberg, William J. McClellan, Debra Montgomery, Vlasios Manaves, Bailin Shaw, Mikkel Algire, Melanie J. Patterson, Chaohong C. Sun, Saul Rosenberg, Albert Lai, Michael R. Michaelides
Summary: The development of a covalent inhibitor targeting p300/CBP has been reported in this study, demonstrating selective binding to C1450. Mass spectrometry and kinetics experiments were used to confirm the covalent binding of the inhibitor, providing a unique tool for studying p300/CBP biology.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Multidisciplinary Sciences
Suguru Hatazawa, Jiuyang Liu, Yoshimasa Takizawa, Mohamad Zandian, Lumi Negishi, Tatiana G. Kutateladze, Hitoshi Kurumizaka
Summary: This study investigates the role of p303 in vital cellular processes and reveals the structures of p300 catalytic core in complex with the nucleosome core particle (NCP) using cryo-electron microscopy. The results show that the HAT domain and bromodomain of p300 interact with nucleosomal DNA at specific locations and that the catalytic site of the HAT domain is positioned near the N-terminal tail of histone H4.
Article
Endocrinology & Metabolism
Viviane S. da Silva, Jussara J. Simao, Victor Plata, Andressa Franca de Sousa, Roberta D. C. da Cunha de Sa, Cleiton Fagundes Machado, Taiza Stumpp, Maria Isabel C. Alonso-Vale, Lucia Armelin-Correa
Summary: This study analyzed the effects of a high-fat diet on the posttranscriptional modifications of H3K27 and the expression of histone-modifying enzymes in adipose-derived stromal cells (ASCs) from white adipose tissue. The results showed that an HFD significantly reduces the acetylation of H3K27 in ASCs and the expression of ATP-citrate lyase in subcutaneous ASCs.
Review
Biochemistry & Molecular Biology
Samuel D. Whedon, Philip A. Cole
Summary: Lysine acetyltransferase (KAT) enzymes are important in modulating chromatin structure and transcription regulation. Recent progress has been made on developing chemical probes for p300 and MYST family of KATs, which can be useful tools for basic and translational research.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yoichi Sunagawa, Ayumi Katayama, Masafumi Funamoto, Kana Shimizu, Satoshi Shimizu, Nurmila Sari, Yasufumi Katanasaka, Yusuke Miyazaki, Ryota Hosomi, Koji Hasegawa, Tatsuya Morimoto
Summary: This study found that both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) suppress cardiomyocyte hypertrophy and the development of heart failure to the same extent through the inhibition of p300-histone acetyltransferase activity.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Alison C. Waldman, Balaji M. Rao, Albert J. Keung
Summary: The article presents a versatile method for studying histone modifications efficiently, with potential for broad applications. By analyzing the writing specificity of histone acetyltransferase on specific residues, and screening the specificity of anti-acetylation antibodies, the complexity of histone modifications is revealed.
CELL CHEMICAL BIOLOGY
(2021)
Article
Biology
Emily Hsu, Nathan R. Zemke, Arnold J. Berk
Summary: The regulation of transcriptional elongation through promoter region histone H3 acetylation, especially by recruitment of the super-elongation complex dependent on CBP/p300, is an important mechanism that applies to about 7% of expressed protein-coding genes in human airway epithelial cells. The maintenance of promoter H3K18/27ac, but not enhancer H3K18/27ac, in response to inhibition of CBP/p300 acetyl transferase activity reveals a homeostatic mechanism that contributes to regulating gene expression. Additionally, the association of BRD4 at enhancers plays a role in controlling the release of paused Pol2 at nearby promoters.
