Review
Oncology
Wen Zong, Yamin Gong, Wenli Sun, Tangliang Li, Zhao-Qi Wang
Summary: This review article discusses the diverse functions of PARP1 in the regulation of gene expression, focusing on the interaction with transcription factors and the chromatin remodeling dependent or independent of DNA damage. The molecular action mode of PARP1 in gene transcription may present as a potential target for therapeutic intervention of inflammation-related diseases and also for cancer therapy.
Article
Multidisciplinary Sciences
Soon-Keat Ooi, Shigeo Sato, Chieri Tomomori-Sato, Ying Zhang, Zhihui Wen, Charles A. S. Banks, Michael P. Washburn, Jay R. Unruh, Laurence Florens, Ronald C. Conaway, Joan W. Conaway
Summary: PARP1 has multiple functions in ALC1-dependent nucleosome remodeling beyond simply synthesizing PAR chains, as shown by investigation of separation-of-function mutants that activate ALC1 ATPase but do not support nucleosome remodeling by ALC1.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Shanshan Guo, Shuang Zhang, Yixiao Zhuang, Famin Xie, Ruwen Wang, Xingyu Kong, Qiongyue Zhang, Yonghao Feng, Huanqing Gao, Xingxing Kong, Tiemin Liu
Summary: Inhibition of PARP1 can extend the lifespan of Drosophila, particularly in muscle. Inhibition of PARP1 increases AMPKα activity and mitochondrial turnover, leading to improved resistance to starvation, oxidative stress, and enhanced climbing ability in older flies. Maintaining mitochondrial network homeostasis requires the involvement of PINK1. These findings suggest that the interaction between PARP1 and AMPKα can manipulate mitochondrial turnover and be targeted to promote longevity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Johannes Rudolph, Genevieve Roberts, Karolin Luger
Summary: PARP1 and PARP2 are key enzymes in the DNA damage response. HPF1 plays an essential role in modulating the PARylation of histones by forming a complex with both PARP1 and PARP2. Results show how HPF1 can affect the binding affinity of certain inhibitors to PARP1.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Arnold Tan, Awais Z. Younis, Alexander Evans, Jade V. Creighton, Clare Coveny, David J. Boocock, Craig Sale, Gareth G. Lavery, Amanda S. Coutts, Craig L. Doig
Summary: The PARP1 enzyme generates and applies ADP-Ribose, a post-translational modification. PARP1 plays important roles in genome maintenance, cellular identity, and energy homeostasis. In skeletal muscle cells, PARP1-mediated PARylation regulates the myogenic program and the muscle response to steroid hormones. PARylation is sensitive to glucose concentrations and glucocorticoids, which are crucial for muscle development and metabolism. PARP1 also influences the transcriptional activation of specific genes critical to skeletal muscle pathology, providing potential targets for selective glucocorticoid modulation.
CELL DEATH DISCOVERY
(2023)
Article
Biochemistry & Molecular Biology
Natasa Ilic, Yulei Tao, Sandy Boutros-Suleiman, Venkata Narasimha Kadali, Andrea Emanuelli, Gal Levy-Cohen, Michael Blank
Summary: SMURF2, a HECT-type E3 ubiquitin ligase, physically interacts with PARP1 in different cellular settings, directly ubiquitinates it in vitro and stimulates its PARylation activity in cells, playing a crucial role in the regulation of PARP1.
Article
Oncology
Fei Shi, Lei Wu, Di Cui, Menghao Sun, Yuanhao Shen, Zheng Zhou, Zheng Deng, Bangmin Han, Shujie Xia, Zheng Zhu, Feng Sun
Summary: FALEC is an oncogenic lncRNA in prostate cancer and its upregulation is associated with poor survival in post-castration PCa patients. It directly interacts with PARP1 and regulates its self PARylation through recruiting ART5. The combination of FALEC depletion and PARP1 inhibitor can inhibit tumor growth and metastasis in castration-resistant prostate cancer.
Review
Oncology
Xifeng Xiong, Xudong Lai, Aiguo Li, Zhihe Liu, Ningfang Ma
Summary: CHD1L is a multifunctional protein involved in regulating chromosomal integrity maintenance, DNA repair, and transcriptional regulation. It acts as an anti-apoptotic and pro-proliferative factor through its binding to DNA, and its overexpression can lead to dysregulation of downstream targets in various cancers. Recent research is shedding light on the molecular basis of CHD1L in normal cells and its role in tumorigenesis, suggesting further study is warranted in both basic biology and clinical applications.
BIOMARKER RESEARCH
(2021)
Review
Oncology
Saptarshi Sinha, Sefinew Molla, Chanakya Nath Kundu
Summary: Cancer progression requires tumorigenic mutations in genes encoding various proteins, with chromatin remodeling playing a crucial role in regulating the expression of these mutated genes. PARP1-mediated chromatin remodeling is important in cancer therapy and can be targeted to reverse drug resistance.
Article
Cell Biology
Natalya Maluchenko, Darya Koshkina, Anna Korovina, Vasily Studitsky, Alexey Feofanov
Summary: The cytotoxicity of poly(ADP-ribose-)polymerase-1 (PARP1) inhibitors (PARPi) in antitumor therapy is correlated with their trapping efficiency in cell chromatin. The interactions of PARP1-nucleosome complexes with PARPi were studied, and it was found that the efficiency of PARP1 trapping on nucleosomes is affected by the chromatin structure.
Article
Pharmacology & Pharmacy
Zhenzhen Li, Zhen Guo, Rui Lan, Sidong Cai, Zhirong Lin, Jingyan Li, Junjian Wang, Zhuoming Li, Peiqing Liu
Summary: BRD4 is crucial in the pathogenesis of cardiac hypertrophy by interacting with PARP1 to induce hypertrophic gene expression and transcription activation. Targeting the inhibition of PARP1-BRD4 interactions may have therapeutic potential for pathological cardiac hypertrophy.
ACTA PHARMACEUTICA SINICA B
(2021)
Review
Cell Biology
Taylor Lovsund, Fatemeh Mashayekhi, Amira Fitieh, James Stafford, Ismail Hassan Ismail
Summary: Detailing the connection between enzymatic families' homeostatic functions and tumorigenesis is crucial for understanding anti-cancer therapies. The PARP family, particularly known for its role in DNA repair and genomic stability, has multiple members involved in these processes. While several PARP inhibitors have been approved for clinical use, resistance to PARPi therapy is growing and requires new counter-resistance mechanisms. This review provides updated understanding of the homeostatic functions mediated by the PARP family, emphasizes the importance of PARPi therapies as anti-cancer agents, and discusses resistance mechanisms and counter-strategies.
Article
Genetics & Heredity
Byeong Jin Ye, Hyun Je Kang, Whaseon Lee-Kwon, Hyug Moo Kwon, Soo Youn Choi
Summary: Research has found that TonEBP can mediate resistance to cell death induced by DNA-damaging agents in cancer cells by preventing the accumulation of R-loops. This discovery contributes to understanding the impact of R-loop formation on genomic stability.
Article
Multidisciplinary Sciences
Li Wang, Kangjing Chen, Zhucheng Chen
Summary: ALC1, an oncogenic chromatin remodeler, plays a crucial role in DNA repair by relaxing chromatin. The study reveals the crystal structure of ALC1 and how it is activated by binding to nucleosomes.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Guangliang Wang, Xiaofeng Zhang, Wei Cheng, Yanxuan Mo, Juan Chen, Zhiming Cao, Xiaogang Chen, Huiqin Cui, Shanshan Liu, Li Huang, Ming Liu, Lei Ma, Ning-Fang Ma
Summary: CHD1L has been identified as a driver gene in hepatocellular carcinoma (HCC), and it promotes nmMYLK expression to prevent LPS-induced tumor cell death. A specific correlation between CHD1L and nmMYLK, a molecule associated with NF-kappa B signaling transduction, was disclosed in HCC, shedding light on a new potential target for HCC treatment.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Yi-Ping Yang, Chian-Shiu Chien, Aliaksandr A. Yarmishyn, Man-Sheung Chan, Andy Chi-Lung Lee, Yi-Wei Chen, Pin- Huang, Hsin- Ma, Wen-Liang Lo, Yueh Chien, Wen-Chang Lin, Mong-Lien Wang, Ming-Teh Chen
Summary: Glioblastoma (GBM) is the most lethal type of brain cancer, where the differentiation of M2 macrophages by MSI1 and MIF1 proteins in the tumor microenvironment promotes tumor progression.
Review
Biochemistry & Molecular Biology
Yu-Jen Chen, Chian-Shiu Chien, Chern-En Chiang, Chen-Huan Chen, Hao-Min Cheng
Summary: Heart failure is a syndrome caused by various important etiologies, and understanding genetic pathophysiology may lead to new therapies for improving HF prognosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Chiu-Yang Lee, Chih-Heng Huang, Elham Rastegari, Vimalan Rengganaten, Ping-Cheng Liu, Ping-Hsing Tsai, Yuan-Fan Chin, Jing-Rong Wu, Shih-Hwa Chiou, Yuan-Chi Teng, Chih-Wei Lee, Yanwen Liang, An-Yu Chen, Shu-Chen Hsu, Yi-Jen Hung, Jun-Ren Sun, Chian-Shiu Chien, Yueh Chien
Summary: Using iPSC-derived cardiomyocytes as a model, the study found that SARS-CoV2 infection can cause cardiomyocyte damage. Pretreatment with TNF-alpha enhances SARS-CoV2 entry, indicating a potential role in cytokine storm and aggravation of myocardial damage in COVID-19 patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Afeez Adekunle Ishola, Chian-Shiu Chien, Yi-Ping Yang, Yueh Chien, Aliaksandr A. Yarmishyn, Ping-Hsing Tsai, Jerry Chieh-Yu Chen, Po-Kuei Hsu, Yung-Hung Luo, Yuh-Min Chen, Kung-Hou Liang, Yuan-Tzu Lan, Teh-Ia Huo, Hsin- Ma, Ming-Teh Chen, Mong-Lien Wang, Shih-Hwa Chiou
Summary: Lung cancers, particularly non-small cell lung cancers, have a poor prognosis. A circular noncoding RNA called C190 has been identified as a negative prognostic biomarker for lung cancer, and this study explores its mechanistic function and potential as a therapeutic target for NSCLC.
Article
Biochemistry & Molecular Biology
Yung-Hung Luo, Yi-Ping Yang, Chian-Shiu Chien, Aliaksandr A. Yarmishyn, Afeez Adekunle Ishola, Yueh Chien, Yuh-Min Chen, Ping-Hsing Tsai, Tzu-Wei Lin, Mong-Lien Wang, Shih-Hwa Chiou
Summary: Lung cancer is the leading cause of death from cancer in Taiwan and worldwide. Immunotherapy has shown promising efficacy in non-small cell lung cancer (NSCLC) by blocking the PD-1/PD-L1 signaling pathway. Circular RNAs (circRNAs) have been identified as potential blood-based biomarkers to monitor the disease progression and immunotherapy efficacy. Hsa_ circ_0000190 was found to interfere with anti-PD-L1 antibody and T-cell activation, leading to immunotherapy resistance and poor prognosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Yi-Ping Yang, Andy Chi-Lung Lee, Liang-Ting Lin, Yi-Wei Chen, Pin- Huang, Hsin- Ma, Yi-Chen Chen, Wen-Liang Lo, Yuan-Tzu Lan, Wen-Liang Fang, Chien-Ying Wang, Yung-Yang Liu, Po-Kuei Hsu, Wen-Chang Lin, Chung-Pin Li, Ming-Teh Chen, Chian-Shiu Chien, Mong-Lien Wang
Summary: This study presents a new therapeutic strategy for GBM tumor by targeting the protein-protein interaction between MSI1 and AGO2 with synthetic peptides. The decoy peptides identified from the C-terminus of MSI1 showed promising therapeutic efficacy in suppressing tumor growth and prolonging survival rates. These findings provide a new rationale for developing targeted therapeutics for GBM.
Correction
Virology
Hsu-Feng Chu, Shu-Chun Cheng, Chiao-Yin Sun, Chi-Yuan Chou, Ta-Hsien Lin, Wei-Yi Chen
JOURNAL OF VIROLOGY
(2022)
Article
Cell Biology
Jun Wang, Xufen Yu, Weida Gong, Xijuan Liu, Kwang-Su Park, Anqi Ma, Yi-Hsuan Tsai, Yudao Shen, Takashi Onikubo, Wen-Chieh Pi, David F. Allison, Jing Liu, Wei-Yi Chen, Ling Cai, Robert G. Roeder, Jian Jin, Gang Greg Wang
Summary: The study reveals the noncanonical oncogenic roles of EZH2 in acute leukaemia, demonstrating its additional functions in binding cMyc and activating gene expression. To target the multifaceted tumorigenic functions of EZH2, the researchers developed a degrader, MS177, which effectively depletes both canonical and noncanonical complexes of EZH2 and shows a faster and more potent effect in suppressing cancer growth.
NATURE CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Zhihong Ren, Arum Kim, Yu-Ting Huang, Wen-Chieh Pi, Weida Gong, Xufen Yu, Jun Qi, Jian Jin, Ling Cai, Robert G. Roeder, Wei-Yi Chen, Gang Greg Wang
Summary: Acute myeloid leukemias (AMLs) with NUP98-NSD1 or MLL-r have stemness-related gene signatures and poor prognosis. Inhibiting EZH2 enzymatic activity shows that PRC2 is crucial for tumorigenicity in NUP98-NSD1(+) AML, and Kdm5b is directly repressed by PRC2. Kdm5b not only suppresses AML growth but also attenuates the anti-AML effects of PRC2 inhibitors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Hsueh-Tzu Shih, Wei-Yi Chen, Hsin-Yen Wang, Tung Chao, Hsien-Da Huang, Chih-Hung Chou, Zee-Fen Chang
Summary: This study investigates how DNMT3b dysfunction leads to genome instability using DNMT3b knockout cells and ICF cells. It demonstrates that R-loops contribute to DNA damages in DNMT3b knockout and ICF cells, and the loss of DNMT3b expression and p53 mutation contribute to more prominent DNA damage signal. In addition, XPG and XPF endonucleases play a role in removing (peri-)centromeric R-loops, causing DNA breaks and chromosome instability.
CELL DEATH & DISEASE
(2022)
Article
Materials Science, Multidisciplinary
Meng-Shiue Lee, Yueh Chien, Pai-Chi Teng, Xuan-Yang Huang, Yi-Ying Lin, Ting-Yi Lin, Shih-Jie Chou, Chian-Shiu Chien, Yu-Jer Hsiao, Yi-Ping Yang, Wensyang Hsu, Shih-Hwa Chiou
Summary: This study demonstrates that the doubly reentrant topology (DRT) surfaces have a significant antibiofouling effect that can effectively prevent viral contamination. This effect still exists even if the DRT surface is made of a hydrophilic material. By minimizing the contact area between pathogens and surfaces, fomite transmission of viruses can be effectively prevented. The unique geometric features of DRT surfaces also contribute to their excellent antibiofouling ability, which may shed light on pathogen elimination in alleviating the COVID-19 pandemic.
ADVANCED MATERIALS TECHNOLOGIES
(2023)
Article
Cell Biology
Chih-Jung Chen, Ya-Chuan Hu, Yueh Chien, Wei-Chieh Huang, Chi-Sheng Wu, Chung-Ying Tsai, Yang-Hsiang Lin, Meng-Shiue Lee, Chian-Shiu Chien, Yi-Ping Yang, Meng-Chou Lee, Chung-Chih Tseng, Hsiang-Cheng Chi
Summary: This study reveals the correlation between the malignancy of neuroblastoma (NB) cells and the expression of Calreticulin (CALR), as well as their radioresistant and stem cell properties. Manipulating CALR expression can alter the stem cell characteristics and radioresistance of NB cells. CALR overexpression increases ROS production and secretion of proinflammatory cytokines, significantly inhibiting the growth of NB tumors, especially when combined with radiotherapy.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2023)
Article
Multidisciplinary Sciences
Chung-Chi Liao, Yi-Sen Wang, Wen-Chieh Pi, Chun-Hsiung Wang, Yi-Min Wu, Wei-Yi Chen, Kuo-Chiang Hsia
Summary: The authors present a cryo-EM structure of Kap114p, revealing a non-canonical function beyond nuclear transport that modulates yTBP-dependent transcription.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Karen G. Rosal, Wei-Yi Chen, Bon-chu Chung
Summary: The study reveals that overexpression of CYP11A1 leads to the formation of tubulovesicular cristae in mitochondria and identifies specific regions of CYP11A1 that are involved in mitochondrial structural changes. The study also uncovers the interaction of CYP11A1 with Hsp60, which plays a crucial role in the accumulation of CYP11A1. Additionally, overexpression of CYP11A1 results in the reduction of the mitochondrial contact site and cristae organizing system.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
Article
Virology
Hsu-Feng Chu, Shu-Chun Cheng, Chiao-Yin Sun, Chi-Yuan Chou, Ta-Hsien Lin, Wei-Yi Chen
Summary: In this study, the crystal structure of porcine epidemic diarrhea virus (PEDV) papain-like protease 2 (PLP2) in complex with ubiquitin (Ub) was reported. The analysis revealed the interactions between PEDV PLP2 and the Ub substrate. Furthermore, the study identified key residues and a conformational feature of PEDV PLP2 that contribute to its function. These findings provide structural insights into the mechanistic effects of PEDV PLP2.
JOURNAL OF VIROLOGY
(2022)
