Article
Chemistry, Medicinal
Andrew M. Asberry, Xinpei Cai, Xuehong Deng, Ulises Santiago, Sheng Liu, Hunter S. Sims, Weida Liang, Xueyong Xu, Jun Wan, Wen Jiang, Carlos J. Camacho, Mingji Dai, Chang-Deng Hu
Summary: Protein arginine methyltransferase 5 (PRMT5) is a crucial epigenetic regulator and a validated therapeutic target in multiple cancers. Researchers have developed a novel small-molecule inhibitor, compound 17, which can target the protein-protein interaction between PRMT5 and MEP50. In vitro experiments demonstrated that compound 17 inhibits PRMT5 and MEP50 substrate methylation selectively, with an IC50 < 500 nM in prostate and lung cancer cells. It also dysregulates the TGF-beta signaling pathway according to RNA-seq analysis. This study provides proof of concept for targeting PRMT5:MEP50 protein-protein interaction and supports further preclinical development of inhibitors in this class.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Charles Brobbey, Shasha Yin, Liu Liu, Lauren E. Ball, Philip H. Howe, Joe R. Delaney, Wenjian Gan
Summary: Protein arginine methyltransferase 5 (PRMT5) catalyzes methylation on arginine residues and has potential as an antitumor target. This study shows that autophagy blockage increases the sensitivity of triple negative breast cancer cells to PRMT5 inhibitor. PRMT5 mediates autophagy by methylating ULK1, and inhibition of ULK1 enhances the therapeutic effect of PRMT5 inhibitor. These findings suggest the combination of PRMT5 and autophagy inhibitors as a potential strategy in cancer therapy.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Shuangjie Liu, Zhuonan Liu, Chiyuan Piao, Zhe Zhang, Chuize Kong, Lei Yin, Xi Liu
Summary: The study reveals PRMT5 as a therapeutic target for bladder cancer and identifies FKA, extracted from the kava plant, as an inhibitor of PRMT5 for the treatment of bladder cancer.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Developmental Biology
E. Nibona, C. Niyonkuru, X. Liang, Q. Yao, H. Zhao
Summary: The PRMT5-MEP50 complex plays a crucial role in various pathways, with a preference for histone substrates such as H2AR3, H4R3, H3R2, and H3R8. Loss of PRMT5 or MEP50 leads to deficiencies, highlighting the potential for drug design against diseases associated with overexpression of PRMT5-MEP50.
RUSSIAN JOURNAL OF DEVELOPMENTAL BIOLOGY
(2021)
Article
Microbiology
Xiaohui Ju, Yanying Yu, Wenlin Ren, Lin Dong, Xianbin Meng, Haiteng Deng, Yuchen Nan, Qiang Ding
Summary: This study systematically analyzed the host factors in HEV replication complex using ORF1 trans-complementation system and HEV replicon. The PRMT5/WDR77 complex was found to have an inhibitory role in HEV infection among different HEV strains, but not in HCV and SARS-CoV-2 infection. The complex methylates the 458th arginine in HEV ORF1, which is responsible for HEV replication. The findings provide insights into HEV replication and viral-host interaction, and inform antiviral strategies against HEV infection.
Article
Immunology
Yingxia Zheng, Zheyi Chen, Bingqian Zhou, Shiyu Chen, Li Han, Ningdai Chen, Yanhui Ma, Guohua Xie, Junyao Yang, Hong Nie, Lisong Shen
Summary: This study found that PRMT5 is important for T cell subset differentiation and antitumor immunity. PRMT5 deficiency promotes CD8(+) T cell differentiation into terminal effector cells and impairs the transition to memory precursor cells. Additionally, PRMT5 deficiency accelerates tumor progression.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Shayaan Rasheed, Renee A. Bouley, Ryan J. Yoder, Ruben C. Petreaca
Summary: Arginine methylation is an important posttranslational modification that regulates various cellular functions. PRMT5, an enzyme involved in arginine methylation, has been studied as a potential target for cancer treatment. This report analyzed PRMT5 mutations in cancer cells and identified key driver mutations that may affect the enzyme's activity and splicing, providing insights into the role of PRMT5 mutations in cancer cells and potential directions for targeted inhibition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Hematology
Shelby L. Sloan, Fiona Brown, Mackenzie Long, Christoph Weigel, Shirsha Koirala, Ji-Hyun Chung, Betsy Pray, Lynda Villagomez, Claire Hinterschied, Anuvrat Sircar, Jobeth Helmig-Mason, Alexander Prouty, Eric Brooks, Youssef Youssef, Walter Hanel, Samir Parekh, Wing Keung Chan, Zhengming Chen, Rosa Lapalombella, Lalit Sehgal, Kris Vaddi, Peggy Scherle, Selina Chen-Kiang, Maurizio Di Liberto, Olivier Elemento, Cem Meydan, Jonathan Foox, Daniel Butler, Christopher E. Mason, Robert A. Baiocchi, Lapo Alinari
Summary: Inhibition of PRMT5 in mantle cell lymphoma demonstrated antitumor activity and restored regulatory activity of the cell cycle, apoptotic cell death, and negative regulators of the B-cell receptor-PI3K/AKT signaling pathway. The selective targeting of PRMT5 shows promise as a potential therapy for patients with relapsed/refractory MCL.
Article
Cell Biology
Tian Xia, Ming Liu, Quan Zhao, Jian Ouyang, Bing Chen, Peipei Xu
Summary: PRMT5 is upregulated in multiple myeloma, and its inhibition enhances cell pyroptosis, while the expression of CASP1 negatively correlated with PRMT5 can be restored by suppressing PRMT5, promoting cell pyroptosis in MM.
CELL DEATH & DISEASE
(2021)
Article
Biotechnology & Applied Microbiology
Ying Wu, Zhe Wang, Lu Han, Zhihao Guo, Bohua Yan, Lili Guo, Huadong Zhao, Mengying Wei, Niuniu Hou, Jing Ye, Zhe Wang, Changhong Shi, Suling Liu, Ceshi Chen, Suning Chen, Ting Wang, Jun Yi, JianPing Zhou, Libo Yao, Wenxia Zhou, Rui Ling, Jian Zhang
Summary: Cancer cells regulate their response to the chemotherapeutic drug doxorubicin through RNA m6A modification. They do this by inhibiting RNA m6A modification through PRMT5 and enhancing the nuclear translocation of the demethylase ALKBH5. This leads to increased DNA repair ability and decreased efficacy of doxorubicin. The approved drug tadalafil was identified as a PRMT5 inhibitor that could enhance doxorubicin sensitivity in breast cancer cells by decreasing RNA m6A methylation.
Article
Biochemistry & Molecular Biology
Melody D. Fulton, Tran Dang, Tyler Brown, Y. George Zheng
Summary: This study explores how local changes on adjacent residues in histone substrate regulate the activities of PRMT1 and PRMT5 enzymes. Phosphorylation at H4S1 inhibits the activity of both enzymes, while the presence of a positively charged H4K5 is important for PRMT1 catalysis. Acetylation of H4K5 or loss of the H4K5 epsilon-amine affects the methylation of H4R3.
Article
Neurosciences
David K. Dansu, Jialiang Liang, Ipek Selcen, Haiyan Zheng, Dirk F. Moore, Patrizia Casaccia
Summary: PRMT5 is an enzyme expressed in oligodendrocyte lineage cells and is responsible for methylating arginine residues on histone tails. Through mass spectrometry and iTRAQ-based proteomics, it was discovered that PRMT5 interacts with numerous proteins and is involved in various molecular functions. Additionally, PRMT5 regulates multiple cellular processes, including RNA processing, transcription, and cell migration, in oligodendrocyte progenitor cells.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Medicine, Research & Experimental
Coralie Poulard, Thuy Ha Pham, Youenn Drouet, Julien Jacquemetton, Ausra Surmielova, Loay Kassem, Benoite Mery, Christine Lasset, Jonathan Reboulet, Isabelle Treilleux, Elisabetta Marangoni, Olivier Tredan, Muriel Le Romancer
Summary: Endocrine therapies targeting estrogen signaling have improved management of estrogen receptor alpha (ERα)-positive breast cancers. However, resistance to treatment remains a challenge. This study identifies nuclear PRMT5 expression as a predictive marker of sensitivity to tamoxifen in breast cancer patients, and reveals the mechanism of tamoxifen stimulating ERα methylation by PRMT5. This biomarker could be used to enhance response to tamoxifen in ERα-positive breast tumors.
EMBO MOLECULAR MEDICINE
(2023)
Article
Oncology
Liu Liu, Shasha Yin, Wenjian Gan
Summary: PRMT5 is overexpressed and activated in various types of cancer, including breast cancer. This study aims to understand the mechanism of how PRMT5 is dysregulated in cancer. The results show that TRAF6-mediated ubiquitination plays a key role in the regulation of PRMT5 activity and cell proliferation. Inhibiting TRAF6 could be a potential strategy for improving PRMT5 targeted therapy.
Article
Biology
Baskar Chakrapani, Mohd Imran K. Khan, Rajashekar Varma Kadumuri, Somlee Gupta, Mamta Verma, Sharad Awasthi, Gayathri Govindaraju, Arun Mahesh, Arumugam Rajavelu, Sreenivas Chavali, Arunkumar Dhayalan
Summary: PRMT5 is an enzyme that symmetrically dimethylates arginine residues in various proteins, and its overexpression is associated with several types of cancers. The study identified FAM47E as an interaction partner of PRMT5, which regulates PRMT5's stability and activity, affecting its functions and levels.
LIFE SCIENCE ALLIANCE
(2021)