Article
Biochemistry & Molecular Biology
Wenyan Yang, Shiqun Wang, Shengqiang Tong, Wei-Dong Zhang, Jiang-Jiang Qin
Summary: This article provides an overview of the ubiquitin-proteasome system (UPS) and its role in pancreatic cancer. Studies indicate that mutations or aberrant expression of UPS members can lead to rewriting of the ubiquitination code, affecting tumor growth, metastasis, immune evasion, and drug resistance. The article also reviews current UPS modulators and analyzes their potential as cancer therapies.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biotechnology & Applied Microbiology
Qiong Wu, Jingru Yin, Min Jiang, Jingyu Zhang, Zhenghong Sui
Summary: This study identified and classified E2 and E3 genes in Gracilariopsis lemaneiformis, an economically important red alga, and analyzed their expression levels and functions during tetrasporophyte development. The results suggest that certain genes may play a crucial role in the fertility of this alga.
Review
Oncology
M. A. A. Mamun, Ying Liu, Yin-Ping Geng, Yi-Chao Zheng, Ya Gao, Jian-Gang Sun, Long-Fei Zhao, Li-Juan Zhao, Hong-Min Liu
Summary: Neddylation is a process that involves adding NEDD8, a protein, to other molecules in neural precursor cells. This process requires three enzymes: activators (E1), conjugators (E2), and ligators (E3). Recent research has highlighted the importance of two specific enzymes, UBE2M and UBE2F, in neddylation and their potential as targets for developing anti-cancer therapies. This evaluation summarizes the current understanding of the interaction between E2 and E1 or E3, and explores the prospects of using neddylation E2 as a pharmacological target for cancer treatment.
Review
Biochemistry & Molecular Biology
Xiaodi Du, Hongyu Song, Nengxing Shen, Ruiqi Hua, Guangyou Yang
Summary: Ubiquitin-conjugating enzymes (E2s) play a vital role in connecting ubiquitin chains to target proteins, regulating the stability and activity of substrate proteins, and participating in various biological processes. Studies have suggested their potential as therapeutic targets in cancer, leading to a need for further exploration of their molecular basis and development of effective drugs targeting E2s.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Daniel Salas-Lloret, Roman Gonzalez-Prieto
Summary: Ubiquitination and SUMOylation are dynamic post-translational modifications that regulate cellular processes. The understanding of these modifications has been increased by the development of mass spectrometry-based approaches. This translated article provides a concise overview of the basic mechanisms of ubiquitination and SUMOylation, as well as recent MS-based approaches for specific target identification.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Veronika Kinterova, Jiri Kanka, Alexandra Bartkova, Tereza Toralova
Summary: SCF-dependent proteolysis, mediated by SCF (Skp1-Cullin 1-F-box) ligases, plays a crucial role in cell cycle regulation, DNA repair, and centrosome cycle. It is also important in oogenesis and embryogenesis, with SCF beta TrCP and SCFSEL-10/FBXW7 being the most studied ligases in these processes. However, there are still many SCF ligases involved in embryogenesis that need to be further elucidated.
Article
Biochemistry & Molecular Biology
Mark A. Nakasone, Karolina A. Majorek, Mads Gabrielsen, Gary J. Sibbet, Brian O. Smith, Danny T. Huang
Summary: This study elucidates the mechanism of processive K48-linked polyUb chain formation by UBE2K, including acceptor Ub recognition and multivalent Ub-binding feature.
NATURE CHEMICAL BIOLOGY
(2022)
Review
Cell Biology
Lisha Zhou, Xiongzhi Lin, Jin Zhu, Luyi Zhang, Siyuan Chen, Hui Yang, Lijun Jia, Baofu Chen
Summary: NEDD8-conjugating enzymes, E2s, including UBE2M and UBE2F, have significant roles in tumor progression. Targeting UBE2M shows therapeutic potential by modulating tumor cell responses or regulating anti-tumor immunity. Inhibitors targeting the UBE2M-DCN1 interaction exhibit promising anti-tumor effects. However, the potential benefits of targeting UBE2F are still to be explored. This review highlights the recent advances and potential of UBE2M and UBE2F as anti-tumor targets.
CELL DEATH DISCOVERY
(2023)
Article
Biochemistry & Molecular Biology
Xiaoxia Shi, Yixin Du, Shujing Li, Huijian Wu
Summary: SUMOylation, a reversible post-translational modification process, plays crucial roles in cell physiology, including cell cycle regulation, DNA damage repair, and protein trafficking and turnover. Dysregulated SUMO E3 ligases may be associated with the occurrence and development of cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Mengmeng Dong, Jinna Zhang, Xiaoyan Han, Jingsong He, Gaofeng Zheng, Zhen Cai
Summary: This study retrospectively analyzed clinical data of 155 MM patients and found that baseline PN was age-related, leading to more severe BiPN during bortezomib induction therapy and worse PN outcome after induction therapy. MM patients with baseline PN also had worse PFS and OS.
SCIENTIFIC REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Yilun Sun, John L. Nitiss, Yves Pommier
Summary: Topoisomerases play crucial roles in DNA metabolism by manipulating DNA structures and are regulated by post-translational modifications. Damage repair of topoisomerase malfunction is also regulated by various conditions and modifications.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Cell Biology
Xiu Yin, Qingbin Liu, Fen Liu, Xinchen Tian, Tinghao Yan, Jie Han, Shulong Jiang
Summary: This review summarizes the role of ubiquitination in tumorigenesis and related signaling pathways, aiming to provide a reference for future exploration of ubiquitination and potential targets for cancer therapies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lukas T. Henneberg, Jaspal Singh, David M. Duda, Kheewoong Baek, David Yanishevski, Peter J. Murray, Matthias Mann, Sachdev S. Sidhu, Brenda A. Schulman
Summary: Researchers have developed conformation-specific antibodies to probe the NEDD8-activated cullin-RING ubiquitin E3 ligase networks in mammalian cells in response to extracellular stimuli, metabolic signals, and degrader drugs.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Vu Thuy Khanh Le-Trilling, Sofia Banchenko, Darius Paydar, Pia Madeleine Leipe, Lukas Binting, Simon Lauer, Andrea Graziadei, Robin Klingen, Christine Gotthold, Joerg Buerger, Thilo Bracht, Barbara Sitek, Robert Jan Lebbink, Anna Malyshkina, Thorsten Mielke, Juri Rappsilber, Christian M. T. Spahn, Sebastian Voigt, Mirko Trilling, David Schwefel
Summary: This study revealed that rat cytomegalovirus infection induces the loss of transcription factor STAT2, which is crucial for antiviral interferon signaling. It was found that viral protein E27 exploits the host-cell CRL4 complexes to degrade STAT2 through poly-ubiquitylation. Furthermore, structural analyses showed that E27 recruits STAT2 through a bipartite binding interface, partially overlapping with the IRF9 binding site.
Review
Cell Biology
Satyendra Chandra Tripathi, Disha Vedpathak, Edwin Justin Ostrin
Summary: Cell-mediated immunity is driven by antigenic peptide presentation on major histocompatibility complex (MHC) molecules. Immunoproteasomes, with inducible activity by inflammatory stimuli, play central roles in cancer, autoimmunity, and inflammation by altering the catalytic activity of the proteasome.Understanding the roles of immunoproteasome in different cancers offers insights into developing targeted therapies.
Article
Hematology
Miguel A. Galindo-Campos, Nura Lutfi, Sarah Bonnin, Carlos Martinez, Talia Velasco-Hernandez, Violeta Garcia-Hernandez, Juan Martin-Caballero, Coral Ampurdanes, Ramon Gimeno, Lluis Colomo, Gael Roue, Guillaume Guilbaud, Francoise Dantzer, Pilar Navarro, Matilde Murga, Oscar Fernandez-Capetillo, Anna Bigas, Pablo Menendez, Julian E. Sale, Jose Yelamos
Summary: Dysregulation of the c-Myc oncogene is linked to aggressive tumor progression, and PARP-1 and PARP-2 have opposing influence in c-Myc-driven B-cell lymphoma. PARP-1 deficiency accelerates lymphomagenesis, while genetic deletion of PARP-2 prevents B-cell lymphoma. These findings provide important insights for the design of new PARP-centered therapeutic strategies.
Review
Biochemistry & Molecular Biology
Miranda Fernandez-Serrano, Rene Winkler, Juliana C. Santos, Marguerite-Marie Le Pannerer, Marcus Buschbeck, Gael Roue
Summary: In lymphoid neoplasms, malignant transformation is often associated with somatic mutations in B cells affecting the epigenetic machinery. Consequential alterations in histone modifications lead to disease-specific changes in transcriptional programs. Therapeutic strategies targeting histone methylation and acetylation show promise in improving the prognosis of lymphoma patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Silvia Saumell, Miranda Fernandez-Serrano, Alba Mesa, Felix Lopez-Cadenas, Leonor Arenillas, Ana Alfonso, Maria Julia Montoro, Antonieta Molero, Pilar Leoz, Victoria Riego, Laura Gallur, Olga Salamero, Mayda Navarrete, Barbara Tazon-Vega, Margarita Ortega, Oscar Reig, Gael Roue, Xavier Calvo, Felipe Prosper, Maria Diez-Campelo, David Valcarcel
Summary: The presence of Micromegakaryocytes (microMKs) in MDS patients indicates poorer outcomes, including lower overall survival rate and higher risk of progression to AML. Additionally, incorporating microMKs into the IPSS-R score can improve accuracy, leading to reclassification of some patients into higher-risk groups.
LEUKEMIA & LYMPHOMA
(2022)
Review
Cell Biology
Ana Maria Montagut, Marc Armengol, Gema Gorjon de Pablo, Roger Estrada-Tejedor, Jose Ignacio Borrell, Gael Roue
Summary: This review provides an update on the major scientific breakthroughs in ubiquitin-targeting therapies in the past decade, with a focus on E1 and E3 modulators. It also discusses the unique challenges of identifying new potential therapeutic targets within this complex system and explores chemical approaches to meet these challenges.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Gregoire Quinet, Wendy Xolalpa, Diana Reyes-Garau, Nuria Profitos-Peleja, Mikel Azkargorta, Laurie Ceccato, Maria Gonzalez-Santamarta, Maria Marsal, Jordi Andilla, Fabienne Aillet, Francesc Bosch, Felix Elortza, Pablo Loza-Alvarez, Brigitte Sola, Olivier Coux, Rune Matthiesen, Gael Roue, Manuel S. Rodriguez
Summary: The research identified an enrichment of autophagy-lysosome system (ALS) components in bortezomib (BTZ)-resistant cells in mantle cell lymphoma (MCL) patients. By blocking proteaphagy, the normal proteasomal activity was reactivated and the BTZ antitumor effect was restored in vitro and in vivo models of BTZ resistance. These findings suggest a proteolytic switch from the ubiquitin-proteasome system (UPS) to ALS in B-cell lymphoma refractory to proteasome inhibition, opening up new therapeutic avenues for treatment-resistant tumors.
Article
Biochemistry & Molecular Biology
Lucas B. Pontel, Alberto Bueno-Costa, Agustin E. Morellato, Juliana Carvalho Santos, Gael Roue, Manel Esteller
Summary: Blood-derived cancer cells are selectively sensitive to compounds blocking the GSH-dependent anti-ferroptosis axis, which may have therapeutic significance for ALL.
Meeting Abstract
Hematology
Miriam Verdu Bou, Maria Joao Baptista, Aleix Mendez Lopez, Gustavo Tapia, Marcelo Lima Ribeiro, Gael Roue, Jose Luis Mate, Pau Abrisqueta, Mariana Bastos-Oreiro, Miguel Alcoceba, Eva Gonzalez Barca, Fina Climent, Antonio Salar, Juan-Manuel Sancho, Fabian Frontzek, Annette M. Staiger, German Ott, Manuel Castro De Moura, Georg Lenz, Jose Tomas Navarro
Correction
Hematology
Ivan Dlouhy, Marc Armengol, Clara Recasens-Zorzo, Marcelo L. Ribeiro, Patricia Perez-Galan, Francesc Bosch, Armando Lopez-Guillermo, Gael Roue
Article
Oncology
Melody Caillot, Hadjer Miloudi, Antoine Taly, Nuria Profitos-Peleja, Juliana C. Santos, Marcelo L. Ribeiro, Elsa Maitre, Simon Saule, Gael Roue, Fabrice Jardin, Brigitte Sola
Summary: By studying the impact of XPO1 gene mutation on protein function, it was found that the mutation renders lymphoma cells more sensitive to SINEs drugs. Additionally, the mutation also leads to mistrafficking of transcription factors between the nucleus and cytoplasm, affecting the response to ibrutinib.
MOLECULAR ONCOLOGY
(2023)
Article
Oncology
Juliana Carvalho Santos, Nuria Profitos-Peleja, Marcelo Lima Ribeiro, Gael Roue
Summary: This study demonstrates that treatment with simvastatin can impede MCL proliferation, inhibit migration and invasion ability, and induce cell death, suggesting the potential of simvastatin as a precise therapy for MCL.
Review
Cell Biology
Juliana Carvalho Santos, Nuria Profitos-Peleja, Salvador Sanchez-Vinces, Gael Roue
Summary: Primarily recognized as a regulator of cytoskeletal dynamics, RHOA is involved in regulating various cellular functions. Deregulated RHOA activity has been linked to cancer growth and metastasis. Recent genomic studies have identified RHOA mutations in leukemia/lymphoma, suggesting its dual role as a tumor promoter or suppressor. Targeting RHOA signaling may offer potential therapeutic strategies for cancer. This review summarizes the molecular mechanisms of RHOA in immune regulation and hematological neoplasms, and discusses current strategies for modulating its activity in these diseases.
Article
Oncology
Marie Sabatier, Rudy Birsen, Laura Lauture, Sarah Mouche, Paolo Angelino, Jonas Dehairs, Ismael Boussaid, Mael Heiblig, Emeline Boet, Ambrine Sahal, Estelle Saland, Juliana C. Santos, Marc Armengol, Miranda Fernandez-Serrano, Thomas Farge, Guillaume Cognet, Federico Simonetta, Corentin Pignon, Antoine Graffeuil, Celine Mazzotti, Herve Avet-Loiseau, Oceane Delos, Justine Bertrand-Michel, Amelie Chedru, Vilma Dembitz, Paolo Gallipoli, Natasha S. Anstee, Sun Loo, Andrew H. Wei, Martin Carroll, Armelle Goubard, Remy Castellano, Yves Collette, Francois Vergez, Veronique Mansat-De Mas, Sarah Bertoli, Suzanne Tavitian, Muriel Picard, Christian Recher, Nathalie Bourges-Abella, Fanny Granat, Olivier Kosmider, Pierre Sujobert, Benoit Colsch, Carine Joffre, Lucille Stuani, Johannes V. Swinnen, Herve Guillou, Gael Roue, Nawad Hakim, Anne S. Dejean, Petros Tsantoulis, Clement Larrue, Didier Bouscary, Jerome Tamburini, Jean-Emmanuel Sarry
Summary: Although the role of CCAAT-enhancer binding protein α (C/EBPα) in cancer cell and metabolic homeostasis is largely unknown, this study reveals its coordination with FLT3 in lipid anabolism and its regulation of fatty acid biosynthesis and desaturation. Furthermore, FLT3 or C/EBPα inactivation decreases monounsaturated fatty acid incorporation and renders FLT3-mutant AML cells vulnerable to ferroptosis. This finding suggests a promising therapeutic potential for targeting FLT3-mutant AML cells.
Review
Hematology
Marcelo Lima Ribeiro, Salvador Sanchez Vinces, Laura Mondragon, Gael Roue
Summary: Non-Hodgkin's lymphomas (NHLs) are a diverse group of diseases characterized by heterogeneous molecular features and clinical manifestations. Epigenetic dysregulations, including mutations in epigenetic enzymes, are prevalent in both B-cell and T-cell lymphomas. Over the past decade, a large number of epigenetic-modifying agents have been developed and introduced in clinical management of NHLs.
THERAPEUTIC ADVANCES IN HEMATOLOGY
(2023)
Meeting Abstract
Oncology
J. Carvalho Santos, N. Profitos Peleja, M. Caillot, S. Sanchez Vinces, B. Sola, M. Lima Ribeiro, G. Roue
EUROPEAN JOURNAL OF CANCER
(2022)