Article
Environmental Sciences
Haojie Li, Junjiang Fan, Yangfei Zhao, Jiarong Yang, Huimiao Xu, Ram Kumar Manthari, Xiaofang Cheng, Jundong Wang, Jinming Wang
Summary: The study shows that long-term excessive intake of fluoride can cause kidney damage and apoptosis, while dietary calcium supplementation can alleviate this damage. Calcium supplementation mitigates fluoride-induced kidney apoptosis through various signaling pathways.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Review
Biochemistry & Molecular Biology
Longfei Deng, Xuan Zhai, Ping Liang, Hongjuan Cui
Summary: TRAIL holds therapeutic potential in cancer treatment, but many cancers, including GBM, exhibit resistance. Recent studies have identified new mechanisms in regulating TRAIL-induced apoptosis in GBM and effective combinatorial strategies. The TRAIL/TRAIL death receptor axis may have future clinical applications for GBM treatment.
Article
Biology
Dongjin Jeong, Hye Sung Kim, Hye Young Kim, Min Jueng Kang, Hyeryeon Jung, Yumi Oh, Donghyun Kim, Jaemoon Koh, Sung-Yup Cho, Yoon Kyung Jeon, Eun Bong Lee, Seung Hyo Lee, Eui-Cheol Shin, Ho Min Kim, Eugene C. Yi, Doo Hyun Chung
Summary: This study shows that sFasL interacts with DR5 to promote inflammation, potentially enhancing it through the CX3CL1-CX3CR1 axis. The interaction plays a role in autoantibody-induced arthritis, possibly mediated through the NF-kappa B pathway.
Article
Hematology
Hilma J. van der Horst, Anne T. Gelderloos, Martine E. D. Chamuleau, Esther C. W. Breij, Sonja Zweegman, Inger S. Nijhof, Marije B. Overdijk, Tuna Mutis
Summary: HexaBody-DRS/DRS antibodies show potential therapeutic efficacy in multiple myeloma, especially exhibiting the highest cytotoxic activity in relapsed/refractory patients who have recently been treated, with synergistic effects observed when combined with other anti-MM drugs such as bortezomib, lenalidomide, and daratumumab.
Review
Biochemistry & Molecular Biology
You-Take Oh, Shi-Yong Sun
Summary: The involvement of the TRAIL/death receptor signaling pathway in the regulation of cancer invasion and metastasis is complex, with both positive and negative roles reported. The underlying molecular mechanisms are even more complicated. This review focuses on discussing the current understanding of how TRAIL/death receptor-mediated signaling regulates cancer cell invasion and metastasis.
Article
Pharmacology & Pharmacy
Chantana Boonyarat, Chavi Yenjai, Prasert Reubroycharoen, Suchada Chaiwiwatrakul, Pitchayakarn Takomthong, Pongput Pimsa, Pornthip Waiwut
Summary: This study investigated the mechanisms behind TRAIL-induced HT29 colon cancer cell death by using heptaphylline and 7-methoxyheptaphylline from Clausena harmandiana. The findings showed that 7-methoxyheptaphylline enhanced the expression of death receptor 5 (DR5) via the JNK pathway, resulting in intensified TRAIL-induced HT29 cell death.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2023)
Review
Physiology
Laurel A. Grisanti
Summary: Cardiovascular disease is a leading cause of death globally. Cardiomyocyte death, which occurs in heart damage and stress, contributes to cardiac dysfunction and further damages the heart. Apoptosis, a regulated form of cell death, can occur through intrinsic or extrinsic pathways. The poorly characterized TNF-related ligand TRAIL and its receptors have been found to play a role in cardiac pathology. This article aims to provide an overview of the current understanding of TRAIL and its receptors in normal and pathological conditions in the heart.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Oncology
Nagamani Vunnam, Malaney C. Young, Elly E. Liao, Chih Hung Lo, Evan Huber, MaryJane Been, David D. Thomas, Jonathan N. Sachs
Summary: Although nimesulide has been taken off the market due to hepatotoxicity, it is still used as a valuable research tool for developing new anticancer drugs. Several studies have been conducted to modify its structure and develop more potent anticancer agents. Understanding the mechanism of action for nimesulide is crucial in realizing its potential.
CANCER BIOLOGY & THERAPY
(2023)
Article
Virology
Xiu-Zhong Zhang, Wen-Jun Tian, Jing Wang, Jing-Ling You, Xiao-Jia Wang
Summary: This study investigates the role of death receptor DR5 in PEDV infection and its relationship with apoptosis. The results demonstrate that the knockdown of DR5 reduces viral levels and induced apoptosis, while overexpression of DR5 increases viral levels. Furthermore, DR5 facilitates viral entry of PEDV.
Article
Biochemistry & Molecular Biology
Lei Chen, Miao Hao, Jingmin Yan, Lin Sun, Guihua Tai, Hairong Cheng, Yifa Zhou
Summary: The active compound DHCP isolated from heat-treated citrus pectin induces cell death in colon cancer cells by inducing mitochondrial ROS, enhances cancer cells sensitivity to TRAIL, and synergistically inhibits the growth of HCT116 and HT-29 xenografts. Furthermore, DHCP increases DR5 expression to further inhibit tumor growth.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Anne Yagolovich, Alina A. Isakova, Artem A. Artykov, Yekaterina V. Vorontsova, Diana Mazur, Nadezhda Antipova, Marat S. Pavlyukov, Mikhail Shakhparonov, Anastasia M. Gileva, Elena A. Markvicheva, Ekaterina A. Plotnikova, Andrey A. Pankratov, Mikhail P. Kirpichnikov, Marine E. Gasparian, Dmitry A. Dolgikh
Summary: In this study, the antitumor activity of DR5-B was improved by fusion with a tumor-homing iRGD peptide, resulting in a promising candidate for targeted therapy for glioblastoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yudong Yin, Li Sun, Lixin Sheng, Liqiong Zhang, Jingjing Liu, Xiaoan Wen, Weibin Mo, Quande Wang, Keguang Cheng
Summary: To discover more effective and less toxic drugs in anti-tumor field, the backbone structure of 17/?-estradiol was modified and 11 target compounds were synthesized. Compounds 5 and 10 showed better anti-tumor activity and higher selectivity, inducing apoptosis in MCF-7 cells and binding to estradiol receptor alpha. They also upregulated the expression of apoptosis-related factors and downregulated anti-apoptotic factors, indicating the induction of cell death through both endogenous and exogenous pathways.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Cell Biology
Barbara Toffoli, Federica Tonon, Veronica Tisato, Giorgio Zauli, Paola Secchiero, Bruno Fabris, Stella Bernardi
Summary: TRAIL induces apoptosis in cancer cells, while its effects in normal cells remain unclear. Studies have shown that TRAIL treatment reduces weight gain, insulin resistance, and inflammation in high-fat diet mice, and promotes skeletal muscle free fatty acid oxidation. Both in vitro and in vivo data demonstrate that TRAIL enhances AKT phosphorylation, skeletal muscle differentiation, and glucose uptake, suggesting therapeutic potential for metabolic disturbances and muscle mass loss associated with diabetes.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Liya Qin, Jian Zou, Alexandra Barnett, Ryan P. Vetreno, Fulton T. Crews, Leon G. Coleman
Summary: The study reports the role of TLR7-mediated apoptotic neuronal death in alcohol use disorder. It suggests that TRAIL may act as a mediator of neuronal apoptosis downstream of TLR7 activation and represent a potential therapeutic target for slowing neurodegeneration in multiple diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Anne Yagolovich, Artem A. Artykov, Alina A. Isakova, Yekaterina V. Vorontsova, Dmitry A. Dolgikh, Mikhail P. Kirpichnikov, Marine E. Gasparian
Summary: In the past two decades, bifunctional proteins have been created to enhance therapeutic effects in various diseases. This study focuses on the design and optimization of a fusion protein, HRH-DR5-B, to enhance the efficacy of the anti-cancer cytokine TRAIL. The optimized SRH-DR5-B fusion protein showed high affinity binding to specific receptors and increased cytotoxic activity in tumor spheroids.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Savithri Ramurthy, Benjamin R. Taft, Robert J. Aversa, Paul A. Barsanti, Matthew T. Burger, Yan Lou, Gisele A. Nishiguchi, Alice Rico, Lina Setti, Aaron Smith, Sharadha Subramanian, Victoriano Tamez, Huw Tanner, Lifeng Wan, Cheng Hu, Brent A. Appleton, Mulugeta Mamo, Laura Tandeske, John E. Tellew, Shenlin Huang, Qn Yue, Apurva Cliaudliary, Hung Tian, Raman Iyer, A. Quamrul Hassan, Lesley A. Mathews Griner, Laura R. La Bonte, Vesselina G. Cooke, Anne Van Abbema, Hanne Merritt, Kalyani Gampa, Fei Feng, Jing Yuan, Yuji Mishina, Yingyun Wang, Jacob R. Haling, Sepideh Vaziri, Mohammad Hekmat-Nejad, Valery Polyakov, Richard Zang, Vijay Sethuraman, Payman Amiri, Mallika Singh, William R. Sellers, Emma Lees, Wenlin Shao, Michael P. Dillon, Darrin D. Stuart
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
David P. Nusinow, John Szpyt, Mahmoud Ghandi, Christopher M. Rose, E. Robert McDonald, Marian Kalocsay, Judit Jane-Valbuena, Ellen Gelfand, Devin K. Schweppe, Mark Jedrychowski, Javad Golji, Dale A. Porter, Tomas Rejtar, Y. Karen Wang, Gregory Kryukov, Frank Stegmeier, Brian K. Erickson, Levi A. Garraway, William R. Sellers, Steven P. Gygil
Article
Oncology
Adam C. Palmer, Deborah Plana, Hui Gao, Joshua M. Korn, Guizhi Yang, John Green, Xiamei Zhang, Roberto Velazquez, Margaret E. McLaughlin, David A. Ruddy, Colleen Kowal, Julie Muszynski, Caroline Bullock, Stacy Rivera, Daniel P. Rakiec, GiNell Elliott, Paul Fordjour, Ronald Meyer, Alice Loo, Esther Kurth, Jeffrey A. Engelman, Hans Bitter, William R. Sellers, Juliet A. Williams, Peter K. Sorger
Article
Chemistry, Medicinal
Matthew J. LaMarche, Michael Acker, Andreea Argintaru, Daniel Bauer, Julie Boisclair, Homan Chan, Christine Hiu-Tung Chen, Ying-Nan Chen, Zhouliang Chen, Zhan Deng, Michael Dore, David Dunstan, Jianmei Fan, Peter Fekkes, Brant Firestone, Michelle Fodor, Jorge Garcia-Fortanet, Pascal D. Fortin, Cary Fridrich, John Giraldes, Meir Glick, Denise Grunenfelder, Huia-Xiang Hao, Martin Hentemann, Samuel Ho, Andriana Jouk, Zhao B. Kang, Rajesh Karki, Mitsunori Kato, Nick Keen, Robert Koenig, Laura R. LaBonte, Jay Larrow, Gang Liu, Shumei Liu, Dyuti Majumdar, Simon Mathieu, Matthew J. Meyer, Morvarid Mohseni, Rukundo Ntaganda, Mark Palermo, Lawrence Perez, Minying Pu, Timothy Ramsey, John Reilly, Patrick Sarver, William R. Sellers, Martin Sendzik, Michael D. Shultz, Joanna Slisz, Kelly Slocum, Troy Smith, Stanley Spence, Travis Stams, Christopher Straub, Victoriano Tamez, Bakary-Barry Toure, Christopher Towler, Ping Wang, Hongyun Wang, Sarah L. Williams, Fan Yang, Bing Yu, Ji-Hu Zhang, Suzanne Zhu
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Thomas C. Atack, Donald D. Raymond, Christa A. Blomquist, Charisse Flerida Pasaje, Patrick R. McCarren, Jamie Moroco, Henock B. Befekadu, Foxy P. Robinson, Debjani Pal, Lisl Y. Esherick, Alessandra Ianari, Jacquin C. Niles, William R. Sellers
ACS MEDICINAL CHEMISTRY LETTERS
(2020)
Article
Oncology
Liang Chang, Paloma Ruiz, Takahiro Ito, William R. Sellers
Summary: Despite significant successes in clinical settings, the development of cancer targeted therapy remains challenging, with a disappointingly high failure rate. The misapplication of the targeted therapy paradigm to therapeutics targeting pan-essential genes is a key factor contributing to this issue. Strategies to avoid previous pitfalls and support the ongoing and future development of pan-essential therapeutics are suggested.
Article
Chemistry, Medicinal
David C. McKinney, Brian J. McMillan, Matthew Ranaghan, Jamie A. Moroco, Merissa Brousseau, Zachary Mullin-Bernstein, Meghan O'Keefe, Patrick McCarren, Michael F. Mesleh, Kathleen M. Mulvaney, Foxy Robinson, Ritu Singh, Besnik Bajrami, Florence F. Wagner, Robert Hilgraf, Martin J. Drysdale, Arthur J. Campbell, Adam Skepner, David E. Timm, Dale Porter, Virendar K. Kaushik, William R. Sellers, Alessandra Ianari
Summary: PRMT5 and its substrate adaptor proteins are essential for methylation of various substrates, including histones and spliceosome complexes. A compound series has been developed that can disrupt PRMT5-Riok1 complexes by binding to the PRMT5-PBM interface, providing a potential new approach for developing selective PRMT5 inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Kathleen M. Mulvaney, Christa Blomquist, Nischal Acharya, Ruitong Li, Matthew J. Ranaghan, Meghan O'Keefe, Diego J. Rodriguez, Michael J. Young, Devishi Kesar, Debjani Pal, Matthew Stokes, Alissa J. Nelson, Sidharth S. Jain, Annan Yang, Zachary Mullin-Bernstein, Josie Columbus, Fazli K. Bozal, Adam Skepner, Donald Raymond, Salvatore LaRussa, David C. McKinney, Yelena Freyzon, Yossef Baidi, Dale Porter, Andrew J. Aguirre, Alessandra Ianari, Brian McMillan, William R. Sellers
Summary: PRMT5 functions as an essential arginine methyltransferase using modular adaptor proteins with a common binding motif for substrate recruitment. Disruption of the PRMT5-substrate adaptor interface impairs the growth of MTAP-null tumor cells, making it a potential target for therapeutic inhibitors of PRMT5.
Editorial Material
Oncology
Francisca Vazquez, William R. Sellers
Summary: CRISPR screens combined with molecular and genetic profiling have systematically identified cancer vulnerabilities, leading to promising drug discovery targets. While systematic loss-of-function studies are still in early stages, the limitations of large-scale screens and cell line models present opportunities for further discovery in oncology research.
Article
Genetics & Heredity
Takahiro Ito, Michael J. Young, Ruitong Li, Sidharth Jain, Andreas Wernitznig, John M. Krill-Burger, Christopher T. Lemke, Davide Monducci, Diego J. Rodriguez, Liang Chang, Sanjukta Dutta, Debjani Pal, Brenton R. Paolella, Michael V. Rothberg, David E. Root, Cory M. Johannessen, Laxmi Parida, Gad Getz, Francisca Vazquez, John G. Doench, Mahdi Zamanighomi, William R. Sellers
Summary: Research using a CRISPR paralog targeting library identified that dual inactivation of DUSP4 and DUSP6 selectively impairs growth in NRAS and BRAF mutant cells. Cells resistant to MAPK pathway therapeutics become cross-sensitized to DUSP4 and DUSP6 perturbations, reinforcing the mechanisms of resistance to the inhibitors.
Article
Multidisciplinary Sciences
Ruitong Li, Olaf Klingbeil, Davide Monducci, Michael J. Young, Diego J. Rodriguez, Zaid Bayyat, Joshua M. Dempster, Devishi Kesar, Xiaoping Yang, Mahdi Zamanighomi, Christopher R. Vakoc, Takahiro Ito, William R. Sellers
Summary: Combinatorial CRISPR screens were used to study genetic interactions and functional redundancies of genes. The authors evaluated ten different CRISPR technologies and identified novel Cas9 tracrRNA combinations with superior performance. The study demonstrates the effectiveness of specific combinatorial approaches for analyzing genetic interactions of multiple genes.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Daniel P. Bondeson, Zachary Mullin-Bernstein, Sydney Oliver, Thomas A. Skipper, Thomas C. Atack, Nolan Bick, Meilani Ching, Andrew A. Guirguis, Jason Kwon, Carly Langan, Dylan Millson, Brenton R. Paolella, Kevin Tran, Sarah J. Wie, Francisca Vazquez, Zuzana Tothova, Todd R. Golub, William R. Sellers, Alessandra Ianari
Summary: Conditional Degron Tags (CDTs) are a valuable tool for validating and studying novel therapeutic targets. In this study, the authors compared five different tags across 16 unique proteins and provided a panel of vectors for users to systematically screen the tags with their own protein of interest.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Ralph Tiedt, Frederick J. King, Christelle Stamm, Matthew J. Niederst, Scott Delach, Sabine Zumstein-Mecker, Jodi Meltzer, Iain J. Mulford, Emma Labrot, Barbara Schacher Engstler, Sabrina Baltschukat, Grainne Kerr, Javad Golji, Daniel Wyss, Christian Schnell, Edward Ainscow, Jeffrey A. Engelman, William R. Sellers, Jordi Barretina, Giordano Caponigro, Diana Graus Porta
Summary: By conducting genome-wide CRISPR screens and large-scale pairwise combination screens, we have identified certain genes, such as MCL1, BCL2L1, and YAP1, that can enhance the sensitivity of lung cancer and colorectal cancer cells to specific drugs, thereby improving therapeutic efficacy. Additionally, through drug combination screens, we have discovered synergistic effects of various drugs across multiple cell lines and identified active triplet combinations for EGFR-mutant lung cancer cells.
Article
Biochemistry & Molecular Biology
Hasmik Keshishian, E. Robert McDonald, Filip Mundt, Randy Melanson, Karsten Krug, Dale A. Porter, Luke Wallace, Dominique Forestier, Bokang Rabasha, Sara E. Marlow, Judit Jane-Valbuena, Ellen Todres, Harrison Specht, Margaret Lea Robinson, Pierre M. Jean Beltran, Ozgun Babur, Meagan E. Olive, Javad Golji, Eric Kuhn, Michael Burgess, Melanie A. MacMullan, Tomas Rejtar, Karen Wang, D. R. Mani, Shankha Satpathy, Michael A. Gillette, William R. Sellers, Steven A. Carr
Summary: SigPath is a targeted mass spectrometry assay that measures various phosphosites in phosphoproteins, allowing for exploration of signaling biology with high throughput and quantitative precision. The assay successfully detected and quantified changes in phospho-signaling in drug-treated cancer cell lines and breast cancer models, highlighting its potential to monitor phosphoproteomic signaling events.
MOLECULAR SYSTEMS BIOLOGY
(2021)
Article
Oncology
Xuewei Wu, Xiaobao Yang, Yan Xiong, Ruitong Li, Takahiro Ito, Tamer A. Ahmed, Zoi Karoulia, Christos Adamopoulos, Hong Wang, Li Wang, Ling Xie, Jing Liu, Beatrix Ueberheide, Stuart A. Aaronson, Xian Chen, Sean G. Buchanan, William R. Sellers, Jian Jin, Poulikos I. Poulikakos
Summary: Research shows that CDK4/6 inhibitors are particularly effective in tumors with low CDK6 expression, while tumors expressing both CDK4 and CDK6 rely more on CDK6. The study reveals that CDK4/6is and CDK4/6 degraders selectively inhibit CDK6 in tumors where it is highly thermo-unstable and associated with the HSP90-CDC37 complex, but are ineffective in tumor cells expressing thermostable CDK6.