Article
Biochemistry & Molecular Biology
Orsolya Bilkei-Gorzo, Tiaan Heunis, Jose Luis Marin-Rubio, Francesca Romana Cianfanelli, Benjamin Bernard Armando Raymond, Joseph Inns, Daniela Fabrikova, Julien Peltier, Fiona Oakley, Ralf Schmid, Anetta Hartlova, Matthias Trost
Summary: This study reveals the importance of phagosomal ubiquitylation and the E3 ubiquitin ligase RNF115 in regulating innate immune functions during bacterial infections.
Article
Biochemistry & Molecular Biology
Moritz Hunkeler, Cyrus Y. Jin, Michelle W. Ma, Julie K. Monda, Daan Overwijn, Eric J. Bennett, Eric S. Fischer
Summary: Recent research has conducted a comprehensive investigation of the HECT ligase HUWE1, deepening our understanding of its molecular structure and function. The study suggests that the N-terminal region of HUWE1 is crucial for ligase function, and cryo-EM structures reveal specific morphological characteristics of HUWE1.
Article
Chemistry, Medicinal
Adam G. Bond, Conner Craigon, Kwok-Ho Chan, Andrea Testa, Athanasios Karapetsas, Rotimi Fasimoye, Thomas Macartney, J. Julian Blow, Dario R. Alessi, Alessio Ciulli
Summary: This study describes the design and development of a new protein degradation system utilizing a variant of the Brd4 bromodomain as a degradation tag. The system effectively degrades BromoTagged proteins in a fast, selective manner, showing favorable pharmacokinetic profile in mice. This system expands the arsenal of chemical genetic degradation tools for manipulating protein levels and exploring therapeutic potential in cells and in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cell Biology
Martin P. Schwalm, Lena M. Berger, Maximilian N. Meuter, James D. Vasta, Cesear R. Corona, Sandra Roehm, Benedict-Tilman Berger, Frederic Farges, Sebastian M. Beinert, Franziska Preuss, Viktoria Morasch, Vladimir V. Rogov, Sebastian Mathea, Krishna Saxena, Matthew B. Robers, Susanne Mueller, Stefan Knapp
Summary: E3 ligases play a crucial role in regulating protein homeostasis by recruiting substrate proteins to the proteasomal degradation machinery. Recent research has focused on the Baculovirus IAP Repeat (BIR) family of E3 ligases, which contain a structurally conserved but diverse protein interaction domain. The Inhibitors of Apoptosis (IAP) family, which typically have three BIR domains, are promising drug targets. However, there is currently a lack of assay tools to evaluate the selectivity of inhibitors in this target area.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Rui Zhang, Shaoqing Shi
Summary: HECT-type E3 ubiquitin ligases play a vital role in controlling protein function and stability, and members of the NEDD4 family have critical roles in dysregulation of autophagy in cancer cells. This review focuses on the role of NEDD4 E3 ligases in defective autophagy in cancer cells, discussing their function, substrates, and signaling pathways, providing a basis for cancer treatment through modulation of these ligases.
MOLECULAR MEDICINE
(2023)
Review
Immunology
Haoran Cui, Yaxian Zhang, Leiliang Zhang
Summary: Poxviruses have evolved various mechanisms to evade innate immunity, some of which involve poxvirus-encoded E3 ubiquitin ligases and adaptor proteins. These proteins can be categorized into five groups based on their functional domains and ubiquitin transfer mechanisms. Most known substrates of poxvirus E3 ubiquitin ligases are components of the innate immune system. Current research progress provides mechanistic insights into the interaction between these viruses and their hosts.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Plant Sciences
Jialing Zhang, Chaonan Li, Long Li, Yajun Xi, Jingyi Wang, Xinguo Mao, Ruilian Jing
Summary: TaAIRP2-1B regulates spike length by facilitating TaHIPP3 degradation, and the haplotype Hap-1B-1 of TaAIRP2-1B is a favorable natural variation for increasing spike length in wheat. This study provides insights into the role of E3 ubiquitin ligase genes in wheat development and identifies TaAIRP2-1B as a key regulator of spike length. The findings also offer genetic resources and markers for wheat molecular breeding.
JOURNAL OF EXPERIMENTAL BOTANY
(2023)
Review
Biochemistry & Molecular Biology
Ishita Tripathi-Giesgen, Christian Behrends, Arno F. Alpi
Summary: The ubiquitin system plays a crucial role in the host cellular defense program against bacterial infection, especially when certain bacteria are exposed to the host cytosol during invasion. Host cell E3 ubiquitin ligases contribute to the formation of a protective ubiquitin coat on invading pathogens, with their divergent ubiquitin conjugation mechanisms influencing the complexity of the anti-bacterial coating. Bacteria have evolved strategies to evade the activities of the host ubiquitin system.
Review
Biochemistry & Molecular Biology
Dong Wang, Yuanming Zou, Xinyue Huang, Zeyu Yin, Mohan Li, Jiaqi Xu, Boquan Wu, Da Li, Ying Zhang, Yingxian Sun, Xingang Zhang, Naijin Zhang
Summary: The ubiquitin-proteasome system is crucial for regulating protein levels in cells, and SMURF1 and SMURF2 are important components that maintain physiological processes by regulating the stability of multiple proteins. The regulatory functions of SMURFs in disease progression are complex, either facilitative or inhibitory, and understanding their mechanisms offers potential therapeutic targets and new avenues for research.
Review
Biochemistry & Molecular Biology
Dong Wang, Yuanming Zou, Xinyue Huang, Zeyu Yin, Mohan Li, Jiaqi Xu, Boquan Wu, Da Li, Ying Zhang, Yingxian Sun, Xingang Zhang, Naijin Zhang
Summary: The ubiquitin-proteasome system plays a crucial role in regulating protein levels in cells. SMURF1 and SMURF2 are key components in this system, responsible for regulating protein stability and maintaining physiological processes such as cell migration, proliferation, and apoptosis. They also play significant roles in disease progression, with complex regulatory functions. This review focuses on the mechanisms by which SMURF1 and SMURF2 regulate disease progression in non-cancerous diseases, providing potential therapeutic targets for various diseases and new research avenues for SMURF proteins.
Article
Biochemistry & Molecular Biology
Yi Zheng, Jian Deng, Lulu Han, Meng-Wei Zhuang, Yanwen Xu, Jing Zhang, Mei-Ling Nan, Yang Xiao, Peng Zhan, Xinyong Liu, Chengjiang Gao, Pei-Hui Wang
Summary: This study reveals the involvement of the stress response pathway and innate antiviral immunity in the pathogenic mechanism of SARS-CoV-2. NSP5 and N protein of SARS-CoV-2 were found to attenuate the formation of antiviral stress granules (avSG). NSP5 suppressed avSG formation and disrupted the RIG-I-MAVS complex to weaken the RIG-I-mediated antiviral response, while N protein specifically targeted cofactors upstream of RIG-I and affected the recognition of dsRNA by RIG-I.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Wenjuan Zhang, Lihui Li, Lili Cai, Yupei Liang, Junfeng Xu, Yue Liu, Lisha Zhou, Chen Ding, Yanmei Zhang, Hu Zhao, Jun Qin, Zhimin Shao, Wenyi Wei, Lijun Jia
Summary: In this study, it was discovered that Prame recognizes p14/ARF for degradation. Inhibiting Prame expression and halting p14/ARF degradation can restrain tumor growth and induce G2/M phase cell cycle arrest.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Biochemistry & Molecular Biology
Qian Lv, Liqun Li, Ying Meng, Huimin Sun, Liuping Chen, Bingxin Wang, Xuejun Li
Summary: The study revealed that TaGW2-6A interacts with TaAGPS and degrades TaAGPS through the 26S proteasome pathway, influencing seed size. This mechanism provides new insights into the formation of wheat grain weight.
Article
Multidisciplinary Sciences
Xiaolan Liu, Xufeng Cen, Ronghai Wu, Ziyan Chen, Yanqi Xie, Fengqi Wang, Bing Shan, Linghui Zeng, Jichun Zhou, Bojian Xie, Yangjun Cai, Jinyan Huang, Yingjiqiong Liang, Youqian Wu, Chao Zhang, Dongrui Wang, Hongguang Xia
Summary: This study reveals that cisplatin enhances the anti-tumor effect of PD-L1 blockade and upregulates ARIH1 expression, promoting T cell infiltration and sensitizing tumors to immune checkpoint blockade. ARIH1 mediates activation of the STING pathway by ubiquitination and degradation of DNA-PKcs, which is a mechanism of tumor resistance to ICB. Activating ARIH1 is an effective strategy to improve the efficacy of cancer immunotherapy.
NATURE COMMUNICATIONS
(2023)
Review
Immunology
Yiyang Liu, Lu Jiang, Xuemeng Sun, Yixuan Song, Yihan Liu, Leiliang Zhang
Summary: TRIM7 plays significant roles in host defense against viral infections and immune signaling pathways. However, viruses have developed immune evasion mechanisms to counteract its function. Understanding the interaction between TRIM7 and antiviral immunity is crucial for developing innovative treatments for viral diseases.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Pathology
Sung-liang Yu, Yi-jing Hsiao, Wendy A. Cooper, Yoon-la Choi, A. L. E. J. A. N. D. R. O. Aviles-salas, Teh-ying Chou, R. E. N. A. T. A. Coudry, Grigory A. Raskin, Stephen B. Fox, Chao-cheng Huang, Yoon Kyung Jeon, Young-hyeh Ko, Wen-hui Ku, Ghee-young Kwon, C. O. N. N. U. L. L. Leslie, Mei-chun Lin, Pei-jen Lou, C. R. I. S. T. O. V. A. M. Scapulatempo-neto, Saulo Mendoza Ramirez, N. I. K. I. T. A. Savelov, Hyo-sup Shim, Cesar Octavio Lara Torres, Isabela Werneck Cunha, L. A. R. I. S. A. Zavalishina, Yan-ming Chen
Summary: This study assessed the performance of PD-L1 diagnostic assays in NSCLC, HNSCC, and UC. The results showed that the performance of Ventana SP263 and Dako 22C3 assays was comparable in NSCLC and HNSCC. However, in UC, the performance of Ventana SP263 assay was less reliable and may impact treatment decisions.
Article
Oncology
Lavinia Tan, Ben Tran, Jeanne Tie, Ben Markman, Sumi Ananda, Niall C. Tebbutt, Michael Michael, Emma Link, Stephen Q. Wong, Sushma Chandrashekar, Jerick Guinto, David Ritchie, Rachel Koldej, Benjamin J. Solomon, Grant A. McArthur, Rodney J. Hicks, Peter Gibbs, Sarah-Jane Dawson, Jayesh Desai
Summary: BRAF V600E mutant metastatic colorectal cancer is a significant clinical problem. Combination therapy with vemurafenib and small-molecule EGFR inhibitors has shown effectiveness in pre-clinical studies, but clinical investigation is lacking.
CLINICAL CANCER RESEARCH
(2023)
Review
Cell Biology
Benjamin Yongcheng Tan, Stephen B. Fox, Sunil R. Lakhani, Puay Hoon Tan
Summary: Grading of breast phyllodes tumors (PTs) varies due to differences in weighting of grading criteria by pathologists. Key diagnostic criteria include increased stromal cellularity, stromal overgrowth, increased stromal mitoses, stromal atypia, stromal fronding, irregular tumor borders, and/or lesional heterogeneity. Clinical and radiological findings, as well as age, also play important roles in determining the diagnosis.
Review
Cell Biology
Ruwangi Udayasiri, Tongtong Luo, Kylie L. Gorringe, Stephen B. Fox
Summary: Ductal carcinoma in situ (DCIS) is a non-invasive breast tumor with the potential to progress to invasive ductal carcinoma (IDC). The current inability to accurately predict the invasive potential of DCIS leads to both over-treatment and under-treatment in patients. Better understanding of the molecular features of DCIS could improve treatment decision-making and avoid unnecessary side-effects. This review summarizes the current knowledge of DCIS and discusses future research directions.
Article
Cell Biology
Nur Diyana Md Nasir, Valerie C. Y. Koh, Ian A. Cree, Blanca I. I. Ruiz, Javier Del Aguila, Subasri Armon, Stephen B. Fox, Sunil R. Lakhani, Puay Hoon Tan
Summary: In this study, an evidence gap map (EGM) was developed based on the literature cited in the PT chapter of the breast WCT. The EGM revealed a lack of high-level evidence citations and an uneven distribution of references. Future work is needed to bridge evidence gaps and broaden citations.
Editorial Material
Oncology
Benjamin J. Solomon, Todd M. Bauer, Tony S. K. Mok, Geoffrey Liu, Julien Mazieres, Filippo de Marinis, Yasushi Goto, Dong-Wan Kim, Yi-Long Wu, Jacek Jassem, Froylan Lopez Lopez, Ross A. Soo, Alice T. Shaw, Anna Polli, Rossella Messina, Laura Iadeluca, Francesca Toffalorio, Enriqueta Felip
Editorial Material
Oncology
Trudy C. Wu, Annalise Stube, Carol Felix, Denise Oseguera, Tahmineh Romero, Jonathan Goldman, Edward B. Garon, Jay M. Lee, John Glaspy, Aaron E. Lisberg, Chad G. Rusthoven, D. Ross Camidge, Shankar Siva, Benjamin Solomon, Alan Lee, Stephen E. Tenn, Narek Shaverdian, Michael L. Steinberg, Ann C. Raldow, Percy Lee
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2023)
Letter
Oncology
Nicolas Girard, Marina C. Garassino, Benjamin Solomon
JOURNAL OF THORACIC ONCOLOGY
(2023)
Letter
Oncology
Nicolas Girard, Marina C. Garassino, Benjamin Solomon
JOURNAL OF THORACIC ONCOLOGY
(2023)
Article
Oncology
Ross A. Soo, Jean-Francois Martini, Anthonie J. van der Wekken, Shunsuke Teraoka, Roberto Ferrara, Alice T. Shaw, Deborah Shepard, Anna Maria Calella, Anna Polli, Francesca Toffalorio, Pascale Tomasini, Chao-Hua Chiu, Dariusz M. Kowalski, Hye Ryun Kim, Benjamin J. Solomon
Summary: In treatment-naive patients with advanced ALK-positive NSCLC, ctDNA can be used as a biomarker to predict the efficacy of lorlatinib treatment.
JOURNAL OF THORACIC ONCOLOGY
(2023)
Article
Medicine, General & Internal
Adrianus Johannes de Langen, Melissa L. Johnson, Julien Mazieres, Anne -Marie C. Dingemans, Giannis Mountzios, Miklos Pless, Jurgen Wolf, Martin Schuler, Herve Lena, Ferdinandos Skoulidis, Yasuto Yoneshima, Sang-We Kim, Helena Linardou, Silvia Novello, Anthonie J. van der Wekken, Yuanbin Chen, Solange Peters, Enriqueta Felip, Benjamin J. Solomon, Suresh S. Ramalingam, Christophe Dooms, Colin R. Lindsay, Carlos Gil Ferreira, Normand Blais, Cynthia C. Obiozor, Yang Wang, Bhakti Mehta, Tracy Varrieur, Gataree Ngarmchamnanrith, Bjorn Stollenwerk, David Waterhouse, Luis Paz-Ares
Summary: This study compared the efficacy and safety of Sotorasib with standard-of-care treatment in patients with non-small-cell lung cancer (NSCLC) with the KRASG12C mutation. The results showed that compared to docetaxel, Sotorasib significantly increased progression-free survival and had a more favorable safety profile.
Review
Oncology
Grace Chazan, Benjamin J. Solomon
Summary: First-line treatment options for patients with advanced non-small cell lung cancer (NSCLC) whose tumors harbour anaplastic lymphoma kinase (ALK) gene rearrangements have evolved rapidly. Although newer generation ALK inhibitors have demonstrated superiority to crizotinib, head-to-head clinical trials comparing these inhibitors are lacking. Decisions on optimal first-line treatment must be based on analysis of relevant trials and consideration of various factors.
TRANSLATIONAL LUNG CANCER RESEARCH
(2023)
Article
Genetics & Heredity
Daniel R. A. Cox, Tess McClure, Fan Zhang, Boris Ka Leong Wong, Adam Testro, Su Kah Goh, Vijayaragavan Muralidharan, Alexander Dobrovic
Summary: Both graft-specific DNA methylation analysis and donor-recipient genotyping techniques successfully quantified gdcfDNA in patients post-liver transplantation, with significant correlation. While the two techniques performed similarly, gdcfDNA monitoring based on graft-specific DNA methylation patterns in cfDNA offers greater practical advantages and enhances the potential for clinical translation.
Article
Cell Biology
Franco Caramia, Terence P. Speed, Hui Shen, Ygal Haupt, Sue Haupt
Summary: This study found an association between dysregulation of X-chromosome inactivation and survival rate in breast cancer patients, and identified prognostic gene expression features related to chromosome abnormalities, providing new insights into female cancer risks.
Review
Cell Biology
Jia-Min B. Pang, David J. Byrne, Alice R. T. Bergin, Franco Caramia, Sherene Loi, Kylie L. Gorringe, Stephen B. Fox
Summary: In recent years, molecular findings have been incorporated into routine diagnostic practice of anatomical pathology, revolutionizing the field. Spatial transcriptomics, a group of technologies that provide transcriptome-wide expression profiling while preserving spatial origin of the data, allows analysis of highly specific areas within a tissue section and correlation of expression data with morphology, tissue type, and location relative to other structures. Some spatial transcriptomics methods are now compatible with formalin-fixed paraffin-embedded tissue (FFPE), potentially leading to their incorporation in routine anatomical pathology practice.