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
Maoyu Wang, Zhensheng Zhang, Zhizhou Li, Yasheng Zhu, Chuanliang Xu
Summary: With the increasing incidence of bladder cancer, there has been a focus on understanding its mechanism and developing new treatment strategies. The introduction of immune checkpoint inhibitor-based immunotherapy has shown great promise in treating advanced bladder cancer and improving patients' survival. The ubiquitin-proteasome system, which plays a crucial role in various biological processes, has been found to be involved in bladder cancer. This review summarizes the recent progress in understanding the role of E3 ubiquitin ligases and deubiquitinases in bladder cancer tumorigenesis and highlights their implications for bladder cancer immunotherapies.
FRONTIERS IN IMMUNOLOGY
(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
Biochemistry & Molecular Biology
Xin Bai, Jianming Tang
Summary: This article provides a comprehensive review of the roles and molecular mechanisms of tripartite motif (TRIM) proteins in breast cancer. It highlights their importance in breast cancer treatment and suggests that TRIM proteins may be ideal targets for breast cancer therapy.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Review
Pharmacology & Pharmacy
Si-Min Qi, Jinyun Dong, Zhi-Yuan Xu, Xiang-Dong Cheng, Wei-Dong Zhang, Jiang-Jiang Qin
Summary: PROTAC technology is an effective method for degrading target proteins through the ubiquitin-proteasome system, with promising applications in cancer treatment. The first oral PROTACs have shown encouraging results in clinical trials, sparking greater enthusiasm for PROTAC research.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Oncology
Moyang Lv, Weichao Hu, Shengwei Zhang, Lijiao He, Changjiang Hu
Summary: Proteolysis-targeting chimeras (PROTACs) are a promising class of drugs that can effectively target undruggable proteins and have potential applications in cancer therapy. This review provides an overview of PROTAC technology and highlights recent clinical trials, as well as novel findings and strategies to enhance PROTAC antitumor activity.
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
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)
Article
Cell Biology
Lei Feng, Jieqing Wang, Jianmin Zhang, Jingfang Diao, Longguang He, Chaoyi Fu, Hui Liao, Xiaoping Xu, Yi Gao, Chenjie Zhou
Summary: This study comprehensively analyzed the clinical significance of E3 ligases in pancreatic cancer, revealing that RNF223 promotes cancer growth by regulating cell metabolism. Through quantitative proteomics analysis, the study identified the involvement of RNF223 in metabolism-related pathways.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
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.
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
Abhishek Sinha, Prasanna Vasudevan Iyengar, Peter ten Dijke
Summary: TGFβ is a crucial factor influencing cell growth and differentiation, playing a key role in maintaining tissue homeostasis. Disruption of the TGFβ signaling pathway is associated with various diseases, including cancer, and its effects are dependent on cellular context. Ubiquitination modification is an important mechanism influencing TGFβ signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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)
Article
Oncology
Mari Mino-Kenudson, Nolwenn Le Stang, Jillian B. Daigneault, Andrew G. Nicholson, Wendy A. Cooper, Anja C. Roden, Andre L. Moreira, Erik Thunnissen, Mauro Papotti, Giuseppe Pelosi, Noriko Motoi, Claudia Poleri, Elisabeth Brambilla, Mary Redman, Deepali Jain, Sanja Dacic, Yasushi Yatabe, Ming Sound Tsao, Fernando Lopez-Rios, Johan Botling, Gang Chen, Teh-Ying Chou, Fred R. Hirsch, Mary Beth Beasley, Alain Borczuk, Lukas Bubendorf, Jin-Haeng Chung, David Hwang, Dongmei Lin, John Longshore, Masayuki Noguchi, Natasha Rekhtman, Lynette Sholl, William Travis, Akihiko Yoshida, Murry W. Wynes, Ignacio I. Wistuba, Keith M. Kerr, Sylvie Lantuejoul
Summary: The survey reveals heterogeneity in PD-L1 immunohistochemistry testing across regions and laboratories, highlighting the need for additional quality assurance measures, formal training, and standardized reporting.
JOURNAL OF THORACIC ONCOLOGY
(2021)
Article
Oncology
P. Hofman, M. Ilie, E. Chamorey, P. Brest, R. Schiappa, V Nakache, M. Antoine, M. Barberis, H. Begueret, F. Bibeau, C. Bonnetaud, P. Bostroem, P. Brousset, L. Bubendorf, L. Carvalho, G. Cathomas, A. Cazes, L. Chalabreysse, M-P Chenard, M-C Copin, J-F Cote, D. Damotte, L. de Leval, P. Delongova, V. Thomas de Montpreville, A. de Muret, A. Dema, W. Dietmaier, M. Evert, A. Fabre, F. Forest, A. Foulet, S. Garcia, M. Garcia-Martos, L. Gibault, G. Gorkiewicz, D. Jonigk, J. Gosney, A. Hofman, I Kern, K. Kerr, M. Kossai, M. Kriegsmann, S. Lassalle, E. Long-Mira, A. Lupo, A. Mamilos, R. Matej, J. Meilleroux, C. Ortiz-Villalon, L. Panico, A. Panizo, M. Papotti, P. Pauwels, G. Pelosi, F. Penault-Llorca, O. Pop, N. Pote, S. R. Y. Cajal, J-C Sabourin, I Salmon, M. Sajin, S. Savic-Prince, H-U Schildhaus, P. Schirmacher, I Serre, E. Shaw, D. Sizaret, A. Stenzinger, J. Stojsic, E. Thunnissen, W. Timens, G. Troncone, C. Werlein, H. Wolff, J-P Berthet, J. Benzaquen, C-H Marquette, V Hofman, F. Calabrese
Summary: This study evaluated the impact of the COVID-19 outbreak on pathology laboratories in Europe, finding a significant decrease in workload in clinical and molecular pathology, a high proportion of employees working remotely, and the adoption of virtual meetings for training in most laboratories. Improved harmonization of biosafety procedures is needed.
Article
Oncology
Nuria Chic, Stephen J. Luen, Paolo Nuciforo, Roberto Salgado, Debora Fumagalli, Florentine Hilbers, Yingbo Wang, Evandro de Azambuja, Istvan Lang, Serena Di Cosimo, Cristina Saura, Jens Huober, Aleix Prat, Sherene Loi
Summary: The CelTIL score has been identified as a promising biomarker in early-stage HER2-positive breast cancer, showing potential to guide the escalation or deescalation of systemic therapy.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2022)
Letter
Oncology
Jasna Metovic, Fabrizio Bianchi, Marco Barella, Mauro Papotti, Giuseppe Pelosi
JOURNAL OF THORACIC ONCOLOGY
(2021)
Article
Oncology
Helena Verdaguer, Tamara Sauri, Daniel Alejandro Acosta, Magdalena Guardiola, Alexandre Sierra, Jorge Hernando, Paulo Nuciforo, Josep M. Miquel, Cristina Molero, Sandra Peiro, Queralt Serra-Camprubi, Guillermo Villacampa, Susana Aguilar, Ana Vivancos, Josep Tabernero, Rodrigo Dienstmann, Teresa Macarulla
Summary: Cholangiocarcinomas are highly heterogeneous at the molecular level. The classification of actionable molecular alterations according to ESCAT is associated with survival in cholangiocarcinoma patients.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Zhen Shi, Julia Wulfkuhle, Malgorzata Nowicka, Rosa Gallagher, Cristina Saura, Paolo G. Nuciforo, Isabel Calvo, Jay Andersen, Jose Luis Passos-Coelho, Miguel J. Gil-Gil, Begona Bermejo, Debra A. Pratt, Eva M. Ciruelos, Patricia Villagrasa, Matthew J. Wongchenko, Emanuel F. Petricoin, Mafalda Oliveira, Steven J. Isakoff
Summary: This study demonstrates the association between high baseline pAKT levels, mutations in PI3K/AKT pathway components, and the enriched benefit of ipatasertib in TNBC.
CLINICAL CANCER RESEARCH
(2022)
Letter
Oncology
Giuseppe Pelosi
JOURNAL OF THORACIC ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Chiara Ronchini, Sara Gandini, Sebastiano Pasqualato, Luca Mazzarella, Federica Facciotti, Marina Mapelli, Gianmaria Frige', Rita Passerini, Luca Pase, Silvio Capizzi, Fabrizio Mastrilli, Roberto Orecchia, Gioacchino Natoli, Pier Giuseppe Pelicci
Summary: In this study, we found that the probability of infection post-vaccination is significantly lower compared to natural infection, and the duration of infection is shorter. These findings are negatively correlated with circulating antibody levels.
Article
Oncology
Salvatore Pece, Ivana Sestak, Francesca Montani, Micol Tillhon, Patrick Maisonneuve, Stefano Freddi, Kim Chu, Marco Colleoni, Paolo Veronesi, Davide Disalvatore, Giuseppe Viale, Richard Buus, Jack Cuzick, Mitch Dowsett, Pier Paolo Di Fiore
Summary: This study compared two molecular tests for breast cancer patients and found that the StemPrintER Risk Score (SPRS) demonstrated better predictive performance in assessing the risk of distant recurrence. It can help identify high-risk patients and provide guidance for personalized treatment decisions.
EUROPEAN JOURNAL OF CANCER
(2022)
Editorial Material
Oncology
Giuseppe Pelosi
JOURNAL OF THORACIC ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
M. G. Filippone, D. Gaglio, R. Bonfanti, F. A. Tucci, E. Ceccacci, R. Pennisi, M. Bonanomi, G. Jodice, M. Tillhon, F. Montani, G. Bertalot, S. Freddi, M. Vecchi, A. Taglialatela, M. Romanenghi, F. Romeo, N. Bianco, E. Munzone, F. Sanguedolce, G. Vago, G. Viale, P. P. Di Fiore, S. Minucci, L. Alberghina, M. Colleoni, P. Veronesi, D. Tosoni, S. Pece
Summary: The overexpression of CDK12 in breast cancer promotes tumorigenesis and makes the cancer cells vulnerable to therapies targeting folate one-carbon metabolism. CDK12 overexpression is associated with early tumor onset and metastasis and is linked to hyperactivation of the serine-glycine-one-carbon network. CDK12-overexpressing breast tumors show positive response to chemotherapy targeting CDK12-induced metabolic alterations, while being refractory to other types of chemotherapy.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Maria Grazia Filippone, Stefano Freddi, Silvia Zecchini, Silvia Restelli, Ivan Nicola Colaluca, Giovanni Bertalot, Salvatore Pece, Daniela Tosoni, Pier Paolo Di Fiore
Summary: Filippone et al. demonstrate that the frequent activation of PKCs in breast cancer leads to abnormal phosphorylation of the tumor suppressor Numb. Aberrantly phosphorylated Numb affects asymmetric cell division, resulting in expansion of cancer stem cell compartment and aggressive disease course. Asymmetric cell division, controlled by Numb, plays a critical role in preventing uncontrolled expansion of the stem cell compartment. However, in breast cancer, aberrant PKC activation phosphorylates Numb in both progeny, leading to symmetric division and expansion of cancer stem cells.
JOURNAL OF CELL BIOLOGY
(2022)
Letter
Pathology
Giuseppe Pelosi, Angelica Sonzogni
Article
Medicine, Research & Experimental
Chiara Di Malta, Angela Zampelli, Letizia Granieri, Claudia Vilardo, Rossella De Cegli, Laura Cinque, Edoardo Nusco, Salvatore Pece, Daniela Tosoni, Francesca Sanguedolce, Nicolina Cristina Sorrentino, Maria J. Merino, Deborah Nielsen, Ramaprasad Srinivasan, Mark W. Ball, Christopher J. Ricketts, Cathy D. Vocke, Martin Lang, Baktiar Karim, Luisa Lanfrancone, Laura S. Schmidt, W. Marston Linehan, Andrea Ballabio
Summary: Birt-Hogg-Dube (BHD) syndrome is a cancer syndrome characterized by the development of various tumors and caused by loss-of-function mutations in the FLCN gene. In this study, the researchers found that TFEB and TFE3, two transcription factors involved in lysosomal biogenesis and autophagy, play a role in renal cystogenesis and tumorigenesis. They also discovered that inhibiting TFEB or TFE3 could prevent tumor formation in BHD renal tumor cell line-derived xenografts. These findings suggest potential therapeutic strategies targeting TFEB and TFE3 for BHD syndrome.
EMBO MOLECULAR MEDICINE
(2023)
Article
Dermatology
Federica Marocchi, Fernando Palluzzi, Paola Nicoli, Marine Melixetian, Giulia Lovati, Giovanni Bertalot, Salvatore Pece, Pier Francesco Ferrucci, Daniela Bossi, Luisa Lanfrancone
Summary: Despite improvements in the management of metastatic melanoma, there are still patients who do not respond to current therapies. Through a preclinical assay, researchers identified a combination therapy targeting AURKA and MAPK/extracellular signal-regulated kinase kinase that was highly effective in metastatic melanoma. Addition of a fatty acid oxidation inhibitor further improved treatment outcomes.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)