Article
Plant Sciences
Xiaoying Lan, Min Hu, Liling Jiang, Jiamin Wang, Yi Meng, Xinmei Chen, Aochu Liu, Wa Ding, Haichuan Zhang, Huan Zhou, Bingyuan Liu, Guanjie Peng, Siyan Liao, Xin Chen, Jinbao Liu, Xianping Shi
Summary: The natural substance piperlongumine from the herbal medicine Piper longum L. has been found to overcome imatinib resistance in chronic myelogenous leukemia (CML), providing a new therapeutic strategy.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Shuwen Zhang, Shitao Zou, Deyao Yin, Lihong Zhao, Daniel Finley, Zhaolong Wu, Youdong Mao
Summary: This study presents high-resolution cryo-electron microscopy structures of human USP14 in complex with the 26S proteasome, revealing two pathways of proteasome state transitions induced by USP14. The findings also highlight the dynamic USP14-ATPase interactions that decouple ATPase activity from deubiquitylation and introduce regulatory checkpoints in the proteasome function. These results provide insights into the complete functional cycle of the USP14-regulated proteasome and have implications for the development of USP14-targeted therapies.
Review
Biochemistry & Molecular Biology
Seonghyeon Moon, Srinivasan Muniyappan, Sung-Bae Lee, Byung-Hoon Lee
Summary: The 26S proteasome is a key enzyme for intracellular protein degradation, and recent studies have revealed its dynamic conformational states and substrate binding modes. Deubiquitinases play crucial roles in substrate degradation by customizing degradation events based on proteasome conformation and processing steps.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Physical
Tianhao Wang, Jianbo Tong, Xing Zhang, Hao Luo, Lei Xu, Zhe Wang
Summary: Protein degradation and synthesis are crucial for regulating biological activities. USP14, a member of DUBs, plays a critical role in protein degradation. Abnormal expression of USP14 is associated with malignant tumors and other diseases.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Multidisciplinary Sciences
Qing-xin Yu, Jiao-chen Wang, Jun-fei Liu, Lu-xia Ye, Yi-qing Guo, Hai-hong Zheng
Summary: This study investigated the role of ADRM1 in bladder cancer through bioinformatics analysis and immunohistochemical analysis. The results showed that high ADRM1 expression was associated with worse overall survival, enrichment in immune-related pathways, and a positive correlation with immune checkpoints. In the tumor microenvironment, high ADRM1 expression was associated with increased infiltration of CD8+ T cells and macrophages. Furthermore, patients with low ADRM1 expression were found to be sensitive to certain chemotherapy drugs. These findings highlight the prognostic significance of ADRM1 in bladder cancer and its potential as a biomarker and therapeutic target.
SCIENTIFIC REPORTS
(2023)
Article
Cell Biology
Vignesh Srinivasan, Muhammad Yasir Asghar, Sadia Zafar, Kid Toernquist, Dan Lindholm
Summary: USP14 is a deubiquitinating enzyme that interacts with the proteasome and removes poly-ubiquitin chains on target proteins. It plays a role in cellular processes such as cell survival, DNA repair, endocytosis, and the inflammatory response. Inhibition of USP14 by compounds like IU1 can affect cancer cell migration and invasion.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Yu Meng, Huiyan Sun, Yayun Li, Shuang Zhao, Juan Su, Furong Zeng, Guangtong Deng, Xiang Chen
Summary: Ferroptosis is regulated by ubiquitination at post-translational level, in which E3 ubiquitin ligases (E3s) and deubiquitinating enzymes (DUBs) play crucial roles. The dysregulation of ubiquitin system enzymes contributes to the progression of multiple cancers. Understanding the regulatory networks of ferroptosis mediated by E3s or DUBs may provide new opportunities for cancer therapy.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Multidisciplinary Sciences
Wonhee Han, Youngmu Koo, Leila Chaieb, Byeong-Rak Keum, Jin-Kwan Han
Summary: This study identifies UCHL5 as a negative regulator of Wnt signaling and reveals its important role in the regulation of Axin1 protein. The study shows that UCHL5 is required for both the stabilization and the polymerization of Axin1 proteins.
SCIENTIFIC REPORTS
(2022)
Review
Genetics & Heredity
Yosuk Min, Hong-Beom Park, Kwang-Hyun Baek, Sohyun Hwang
Summary: In ovarian cancer, the survival rate is much higher for early stages than for advanced stages. However, most patients are diagnosed in the advanced stages and often experience recurrence. To address this, new biomarkers for early diagnosis and treatment are needed. This review focuses on deubiquitinating enzymes and their regulated substrates in ovarian cancer cells, which could aid in the discovery of biomarkers and therapeutic candidates.
Article
Chemistry, Multidisciplinary
Wa Ding, Jin-xiang Wang, Jun-zheng Wu, Ao-chu Liu, Li-ling Jiang, Hai-chuan Zhang, Yi Meng, Bing-yuan Liu, Guan-jie Peng, En-zhe Lou, Qiong Mao, Huan Zhou, Dao-lin Tang, Xin Chen, Jin-bao Liu, Xian-ping Shi
Summary: 5-Fluorouracil (5-FU) is commonly used to treat colorectal cancer (CRC), but resistance to 5-FU is a major challenge. This study investigated the role of deubiquitinases USP14 and UCHL5 in CRC development and 5-FU resistance. The results showed that inhibiting USP14 and UCHL5 increased 5-FU sensitivity in resistant CRC cells and decreased sensitivity in sensitive CRC cells. Targeting USP14 and UCHL5 with the specific inhibitor b-AP15 suppressed CRC cell viability, proliferation, migration, and induced cell death. B-AP15 also inhibited NF-κB pathway activation. In CRC xenografts, administration of b-AP15 effectively suppressed tumor growth. These findings suggest that targeting USP14 and UCHL5 may be a promising therapeutic strategy for CRC treatment.
ACTA PHARMACOLOGICA SINICA
(2023)
Review
Cell Biology
Yi Xiong, Chao Yu, Qianting Zhang
Summary: This review discusses the functions of ubiquitin proteasome system (UPS) components in mammalian spermatogenesis, including the composition of proteasome isoforms at each stage, the specificity and associated degradation events of each isoform, E3 ubiquitin ligases mediating protein ubiquitination, and the deubiquitinases involved in spermatogenesis and male fertility. Exploring the UPS machineries in spermatogenesis provides insights into protein dynamics during male germ cell production and sheds light on the etiology and pathogenesis of human male infertility.
Article
Biochemistry & Molecular Biology
Ethan L. L. Morgan, Tiffany Toni, Ramya Viswanathan, Yvette Robbins, Xinping Yang, Hui Cheng, Sreenivasulu Gunti, Angel Huynh, Anastasia L. L. Sowers, James B. B. Mitchell, Clint T. T. Allen, Zhong Chen, Carter Van Waes
Summary: TNF alpha is a key mediator of immune, chemotherapy and radiotherapy-induced cytotoxicity, but several cancers display resistance to TNF alpha due to activation of the NF kappa B pro-survival pathway. In this study, we found that the expression of USP14, a proteasome-associated deubiquitinase, is increased in HNSCC and correlates with worse progression free survival. Inhibition or depletion of USP14 inhibited the proliferation and survival of HNSCC cells and reduced NF kappa B activity. Furthermore, we showed that the inhibitor b-AP15 sensitized HNSCC cells to TNF alpha-mediated cell death and radiation-induced cell death, and delayed tumor growth in vivo.
CELL DEATH AND DIFFERENTIATION
(2023)
Review
Biochemistry & Molecular Biology
Karen A. Sap, Karlijne W. Geijtenbeek, Sabine Schipper-Krom, Arzu Tugce Guler, Eric A. Reits
Summary: Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the HTT gene, resulting in the accumulation and toxicity of mutant HTT (mHTT) protein. The ubiquitin-proteasome system (UPS) is involved in clearing mHTT proteins, but the polyQ expansion in mHTT affects its interaction with ubiquitinating enzymes and targeting for degradation. Various ubiquitin-modifying enzymes have been identified that can improve mHTT turnover and overall homeostasis, providing potential targets for therapeutic intervention in HD.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Oncology
Lanyang Gao, Danli Zhu, Qin Wang, Zheng Bao, Shigang Yin, Huiyan Qiang, Heinrich Wieland, Jinyue Zhang, Alexander Teichmann, Jing Jia
Summary: USP7 is overexpressed in melanoma and affects specific proteins and processes through multiple signaling pathways, with knockdown of USP7 slowing down melanoma cell proliferation.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Su Yeon Kim, Ji-young Lee, Yun-jung Cho, Kwan Hoon Jo, Eun Sook Kim, Je Ho Han, Kwang-Hyun Baek, Sung-dae Moon
Summary: This study found that USP37 is a specific deubiquitinating enzyme for CDC73, and the two proteins interact through specific domains, suggesting that USP37 plays an important role in the stability of CDC73 in HPT-JT syndrome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Ilona Berestjuk, Margaux Lecacheur, Alexandrine Carminati, Serena Diazzi, Christopher Rovera, Virginie Prod'homme, Mickael Ohanna, Ana Popovic, Aude Mallavialle, Frederic Larbret, Sabrina Pisano, Stephane Audebert, Thierry Passeron, Cedric Gaggioli, Christophe A. Girard, Marcel Deckert, Sophie Tartare-Deckert
Summary: The study reveals that physical and structural signals from fibroblast-derived ECM can cause the antiproliferative responses to BRAF/MEK inhibitors to fail in melanoma. Drug-induced linear clustering of DDR1 and DDR2 mediates ECM-mediated drug resistance. Targeting DDR1 and DDR2 can overcome resistance to BRAF-targeted therapy mediated by ECM.
EMBO MOLECULAR MEDICINE
(2022)
Article
Multidisciplinary Sciences
Shivalika Tanwar, Patrick Auberger, Germain Gillet, Mario DiPaola, Katya Tsaioun, Bruno O. Villoutreix
Summary: Identification of off-targets is crucial in drug discovery, and FastTargetPred is a method that predicts putative macromolecular targets for small molecule compounds based on chemical similarity search approaches. This study provides a new dataset for target prediction of peptides and includes links to ChEMBL, UniProt, and Reactome databases.
Article
Hematology
Lorric Delage, Mireille Lambert, Cindy Kundlacz, Dimitri Chartoire, Axel Conchon, Lucas Gorka, Patrick Auberger, Arnaud Jacquel, Carole Soussain, Olivier Destaing, Henri -Jacques Delecluse, Susanne Delecluse, Samir Merabet, Alexandra Traverse-Glehen, Gilles Salles, Emmanuel Bachy, Marc Billaud, Herve Ghesqueres, Jean-Pierre Rouaut, Pierre Sujobert
Summary: Understanding the role of mutated genes is crucial for improving cancer treatment. This study focuses on the BTG1 gene, which is frequently mutated in DLBCL. The researchers found that BTG1 deletion accelerates the development of lymphoproliferative disease driven by Bcl2 overexpression. They also discovered that BCAR1 is a partner of BTG1 and that overactivation of the BCAR1-RAC1 pathway increases cell migration ability. The SRC inhibitor dasatinib can target these modifications, providing new therapeutic opportunities for BTG1 mutated DLBCL.
Article
Immunology
Melanie Tichet, Stephan Wullschleger, Agnieszka Chryplewicz, Nadine Fournier, Rachel Marcone, Annamaria Kauzlaric, Krisztian Homicsko, Laura Codarri Deak, Pablo Umana, Christian Klein, Douglas Hanahan
Summary: PD1-IL2v is an engineered immunocytokine that delivers IL2v precisely to PD-1+ T cells in the tumor microenvironment, resulting in infiltration by stem-like CD8+ T cells and enhanced tumor regression and survival in mice. Combining PD1-IL2v with anti-PD-L1 improves therapeutic efficacy by reprogramming tumor-associated macrophages and enhancing T cell receptor immune repertoire diversity. These findings support the clinical evaluation of PD1-IL2v and anti-PD-L1 combination therapy in immunotherapy-resistant tumors infiltrated with PD-1+ stem-like T cells.
Article
Oncology
Lindsay B. Alcaraz, Aude Mallavialle, Caroline Mollevi, Florence Boissiere-Michot, Hanane Mansouri, Joelle Simony-Lafontaine, Valerie Laurent-Matha, Thierry Chardes, William Jacot, Andrei Turtoi, Pascal Roger, Severine Guiu, Emmanuelle Liaudet-Coopman
Summary: The study reveals that SPARC expression in cancer-associated fibroblasts (CAF) is an independent prognostic marker of poor outcome in triple-negative breast cancer (TNBC). The fibroblast-secreted SPARC also has a tumor-promoting role by inhibiting TNBC cell adhesion and stimulating their motility and invasiveness.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Oncology
Zakia Aid, Elie Robert, Cecile K. Lopez, Maxence Bourgoin, Fabien Boudia, Melchior Le Mene, Julie Riviere, Marie Baille, Salima Benbarche, Laurent Renou, Alexandre Fagnan, Cecile Thirant, Laetitia Federici, Laure Touchard, Yann Lecluse, Anton Jetten, Birgit Geoerger, Helene Lapillonne, Eric Solary, Muriel Gaudry, Soheil Meshinchi, Francoise Pflumio, Patrick Auberger, Camille Lobry, Arnaud Petit, Arnaud Jacquel, Thomas Mercher
Summary: Pediatric acute myeloid leukemia expressing the ETO2::GLIS2 fusion oncogene has a poor prognosis. The expression of ETO2::GLIS2 leads to activation of CASP3 and increased cell death. Inhibiting both BCL2 and MCL1 is necessary to prevent disease progression in vivo, suggesting a potential therapeutic strategy for this aggressive pediatric AML subgroup.
Article
Oncology
Anne Calleja, Michael Loschi, Laurent Bailly, Adeline Morisot, Alice Marceau, Lionel Mannone, Guillaume Robert, Patrick Auberger, Claude Preudhomme, Sophie Raynaud, Fabien Subtil, Pierre Sujobert, Thomas Cluzeau
Summary: Personalized medicine is a significant challenge for patients with acute myeloid leukemia (AML). This study evaluated the prognostic value of a personalized prognostic scoring algorithm known as Knowledge Bank (KB) on a cohort of 167 real-life AML patients. The results showed that the KB algorithm accurately predicted outcomes for younger patients in favorable and intermediate ELN risk categories but failed to predict survival for younger patients in the adverse ELN risk category and older patients in the favorable ELN risk category. The discrepancies may be attributed to the emergence of new therapeutic options and improvements in allogeneic stem cell transplantation (aHSCT) outcomes and supportive cares. Therefore, prospective validation of these scoring systems is necessary to incorporate recent therapeutic innovations.
Article
Clinical Neurology
Caroline Ruetsch-Chelli, Darin T. T. Okuda, Fanny Rocher, Sophie Tartare-Deckert, Marcel Deckert, Christine Lebrun-Frenay
Summary: This study investigated the effects of four S1P(1)-RM drugs approved for managing multiple sclerosis on melanoma cell lines in vitro and found that these drugs can promote the proliferation of melanoma cells at therapeutic concentrations. Therefore, increased dermatologic surveillance should be considered for patients with multiple sclerosis receiving S1P(1)-RM treatments.
NEUROLOGY AND THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Kenji F. Shoji, Elsa Bayet, Sabrina Leverrier-Penna, Dahiana Le Devedec, Aude Mallavialle, Severine Marionneau-Lambot, Florian Rambow, Raul Perret, Aurelie Joussaume, Roselyne Viel, Alain Fautrel, Amir Khammari, Bruno Constantin, Sophie Tartare-Deckert, Aubin Penna
Summary: Melanoma, a highly aggressive cancer, is driven by aberrant cell motility behaviors and the ability to rapidly metastasize. This study reveals the prominent expression of the plasma membrane TRPV2 calcium channel in melanoma tumors, directly linked to metastatic dissemination. TRPV2 activity confers migratory and invasive potentials in both in vitro and in vivo settings, while silencing TRPV2 in highly metastatic melanoma cells prevents aggressive behavior. The TRPV2 channel, localized at the leading edge of invasive melanoma cells, regulates calcium-mediated activation of calpain and subsequent cleavage of talin, along with F-actin organization. Overexpression of TRPV2 in human melanoma tissues is associated with advanced malignancy and poor prognosis, suggesting its potential as a biomarker. By controlling adhesion and motility, the mechanosensitive TRPV2 channel offers a new therapeutic option for migrastatics in metastatic melanoma treatment.
Review
Oncology
Serena Diazzi, Sophie Tartare-Deckert, Marcel Deckert
Summary: Advanced cutaneous melanoma is the deadliest form of skin cancer, and targeted therapies and immune checkpoint blockade therapies have revolutionized its treatment. However, therapy-driven resistance remains a significant challenge. Recent studies have shown that phenotypic plasticity of melanoma cells, particularly their ability to adapt mechanically, is a key factor in treatment resistance and tumor relapse. Targeting dedifferentiated cells and mechanotransduction pathways in the extracellular matrix (ECM) may hold promise in overcoming melanoma cross-resistance.
Article
Oncology
Olivia Vidal-Cruchez, Victoria J. Nicolini, Tifenn Rete, Karine Jacquet, Roger Rezzonico, Caroline Lacoux, Marie-Angela Domdom, Barnabe Romeo, Jeremie Roux, Arnaud Hubstenberger, Bernard Mari, Baharia Mograbi, Paul Hofman, Patrick Brest
Summary: Cancer therapies targeting the MAPK pathway lead to drug resistance. Overexpression of RAS has been linked to this resistance, but the underlying mechanisms are unclear. This study shows that MEK inhibitors increase translation of KRAS and NRAS oncogenes through liquid-liquid phase separation, specifically P-body dissolution. This feedback loop involving P-bodies and phase separation could be important for future targeted therapies.
Article
Cell Biology
Sandy Giuliano, Christopher Montemagno, Marie-Angela Domdom, Manon Teisseire, Patrick Brest, Daniel J. Klionsky, Paul Hofman, Gilles Pages, Baharia Mograbi
Summary: Nearly fifty million older people suffer from neurodegenerative diseases, and this number is expected to triple by 2050. Defective lysosomal acidification and impairment of the autophagy pathway have been identified as modifiable risk factors for dementia. The long-term prescribing of lysosomotropic drugs to the elderly, such as proton pump inhibitors, chloroquine, and hydroxychloroquine, may be connected to the incidence of neurodegenerative diseases.