Article
Multidisciplinary Sciences
Daniel S. Park, Son C. Nguyen, Randi Isenhart, Parisha P. Shah, Wonho Kim, R. Jordan Barnett, Aditi Chandra, Jennifer M. Luppino, Jailynn Harke, May Wai, Patrick J. Walsh, Richard J. Abdill, Rachel Yang, Yemin Lan, Sora Yoon, Rebecca Yunker, Masato T. Kanemaki, Golnaz Vahedi, Jennifer E. Phillips-Cremins, Rajan Jain, Eric F. Joyce
Summary: Researchers developed a high-throughput DNA or RNA labeling technology called HiDRO, enabling the quantitative measurement of chromatin interactions in single cells. By screening the human druggable genome, they identified over 300 factors that influence genome folding during interphase, with 43 genes validated to increase or decrease interactions between topologically associating domains. Inhibition of the kinase GSK3A was found to increase long-range chromatin looping interactions in a genome-wide and cohesin-dependent manner. These findings highlight the importance of GSK3A signaling in nuclear architecture and demonstrate the utility of HiDRO for identifying mechanisms of spatial genome organization.
Article
Microbiology
Xuezhang Tian, Yaru Zhou, Shaowei Wang, Ming Gao, Yanlin Xia, Yangyang Li, Yunhong Zhong, Wenhao Xu, Lei Bai, Bishi Fu, Yu Zhou, Hye-Ra Lee, Hongyu Deng, Ke Lan, Pinghui Feng, Junjie Zhang
Summary: In this study, SMCHD1 was identified as a cell-intrinsic restriction factor that controls the replication of KSHV and a wide range of herpesviruses by targeting the origins of viral DNA replication. SMCHD1 deficiency facilitated the replication of a murine herpesvirus in vivo. This study helps us to better understand intrinsic antiviral immunity and could contribute to the development of new therapies for herpesvirus infection and related diseases.
Article
Biology
Olga T. Schubert, Joshua S. Bloom, Meru J. Sadhu, Leonid Kruglyak, Kevin J. Verstrepen
Summary: This article describes a genetic screening method for studying the encoding of protein abundance regulation in the genome. The researchers identified numerous regulatory relationships and revealed the different roles of specific regulators and broad regulators in protein translation.
Article
Biology
Michael C. Kiritsy, Laurisa M. Ankley, Justin Trombley, Gabrielle P. Huizinga, Audrey E. Lord, Pontus Orning, Roland Elling, Katherine A. Fitzgerald, Andrew J. Olive
Summary: Two parallel pathways, involving GSK3β and MED16, control the expression of MHCII induced by IFNγ, and are essential for CD4(+) T cell activation.
Article
Pharmacology & Pharmacy
Lingjie Bao, Zhe Wang, Zhenxing Wu, Hao Luo, Jiahui Yu, Yu Kang, Dongsheng Cao, Tingjun Hou
Summary: In this study, a model called AMGU was developed to predict the inhibitory activities of small molecules against various kinases. The AMGU model outperformed other models on both internal and external test sets, demonstrating its enhanced generalizability. Additionally, a method called edges masking was devised to explain the predictive mechanisms, and a web server called KIP was developed for predicting the polypharmacology effects of small molecules on the kinome.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Oncology
Rajnish Kumar Singh, Dipayan Bose, Erle S. Robertson
Summary: Epigenetic reprogramming of the KSHV genome occurs during hypoxia, leading to enrichment of both transcriptional activator and repressor modifications of histones. KSHV-encoded antigens contribute to the increase in modified histone proteins. Specific regions of the KSHV genome are critical for DNA replication under hypoxic conditions.
Article
Cell Biology
Jinghui Liu, Yue Zhao, Daheng He, Katelyn M. Jones, Shan Tang, Derek B. Allison, Yanquan Zhang, Jing Chen, Qiongsi Zhang, Xinyi Wang, Chaohao Li, Chi Wang, Lang Li, Xiaoqi Liu
Summary: Enzalutamide (ENZA), a second-generation androgen receptor antagonist, enhances the efficacy of treatment for metastatic prostate cancer (PCa), but resistance remains a challenge. Through a CRISPR-Cas9 knockout screen, casein kinase 1a (CK1a) has been identified as a therapeutic target to overcome ENZA resistance. Inhibition of CK1a stabilizes ATM and restores DNA-damage response signaling, leading to increased cell death and growth arrest.
CELL REPORTS MEDICINE
(2023)
Article
Multidisciplinary Sciences
Li-Ting Wang, Marie-Eve Proulx, Anne D. Kim, Virginie Lelarge, Luke McCaffrey
Summary: Proteomics-based screening identified proteins associated with lumen formation, including PARD3B, RALB, and HRNR. Functional analyses revealed their roles as regulators of lumen formation. Additionally, PTPN14 was identified as a component required for maintaining apical-basal polarity.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
John M. Allen, Madison Balagtas, Elizabeth Barajas, Carolina Cano Macip, Sarai Alvarez Zepeda, Ionit Iberkleid, Elizabeth M. Duncan, Ricardo M. Zayas
Summary: This study uncovers the roles of RING/U-box E3 ligases in stem cell regulation and regeneration, and identifies differential gene targets for two putative PRC1 factors required for maintaining cell-type-specific gene expression in planarians.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Natalie M. Garza, Aaron T. Griffin, Mohammad Zulkifli, Chenxi Qiu, Craig D. Kaplan, Vishal M. Gohil
Summary: This study identified novel genetic regulators of mitochondrial copper homeostasis through a genome-wide screen, including subunits of the AP-3 complex and components of the cellular pH-sensing pathway. These genes impact vacuolar acidity, which in turn perturbs mitochondrial copper homeostasis and CcO function. The study provides insights into how vacuolar pH affects mitochondrial respiration through copper homeostasis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Samir H. Barghout, Ahmed Aman, Kazem Nouri, Zachary Blatman, Karen Arevalo, Geethu E. Thomas, Neil MacLean, Rose Hurren, Troy Ketela, Mehakpreet Saini, Moustafa Abohawya, Taira Kiyota, Rima Al-Awar, Aaron D. Schimmer
Summary: The study revealed that the BEND3 gene plays a crucial role in the sensitivity of cancer drug TAK-243, with its knockout reducing the drug's impact on cancer cells. Knocking out BEND3 also affects the expression levels of BCRP, thereby regulating the intracellular levels of the drug TAK-243.
Article
Oncology
Tamar Evron, Michal Caspi, Michal Kazelnik, Yarden Shor-Nareznoy, Shir Armoza-Eilat, Revital Kariv, Zohar Manber, Ran Elkon, Ella H. Sklan, Rina Rosin-Arbesfeld
Summary: The Wnt signaling pathways are crucial in development and adult homeostasis, with aberrant activation implicated in diseases such as cancer. A genome-scale CRISPR-Cas9 knockout screen identified potential Wnt signaling inhibitors, with DHX29 shown to regulate the pathway's activity. These findings suggest DHX29 may act as a novel canonical Wnt signaling tumor suppressor and showcase the utility of this screening approach in identifying new Wnt signaling modulators.
Article
Biochemical Research Methods
Jared T. Miller, Caitlin N. Vitro, Siteng Fang, Samantha R. Benjamin, L. Nathan Tumey
Summary: The study found that novel linkers (AsnAsn) have better stability and efficacy, enhancing drug delivery applications for ADCs and SMDCs.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Sander A. L. Palit, Jeroen van Dorp, Daniel Vis, Cor Lieftink, Simon Linder, Roderick Beijersbergen, Andries M. Bergman, Wilbert Zwart, Michiel S. van der Heijden
Summary: This study identified activated BRAF signaling as a determinant for enzalutamide resistance in prostate cancer cells, and found that combined pharmaceutical targeting of AR and MAPK signaling resulted in strong synergistic inhibition of cell proliferation. The results suggest that co-targeting the MAPK and AR pathways may be effective, particularly in patients harboring oncogenic BRAF mutations.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Yun Zhang, Joana Liu Donaher, Sunny Das, Xin Li, Ferenc Reinhardt, Jordan A. Krall, Arthur W. Lambert, Prathapan Thiru, Heather R. Keys, Mehreen Khan, Matan Hofree, Molly M. Wilson, Ozlem Yedier-Bayram, Nathan A. Lack, Tamer T. Onder, Tugba Bagci-Onder, Michael Tyler, Itay Tirosh, Aviv Regev, Jacqueline A. Lees, Robert A. Weinberg
Summary: Loss of PRC2 or KMT2D-COMPASS enables distinct epithelial-mesenchymal transition (EMT) trajectories in carcinoma cells, with differing effects on metastatic ability. These findings provide insight into how carcinoma cells control their entrance into and residence in different states, and which states are favorable for metastasis.
NATURE CELL BIOLOGY
(2022)
