Article
Biochemistry & Molecular Biology
Jie Huang, Xiaolong Tan, Yan Liu, Kainian Jiang, Jian Luo
Summary: The asymptomatic nature of cholangiocarcinoma (CCA) during its early stages, combined with its high aggressiveness and chemoresistance, significantly affect the effectiveness of current treatments. The abnormal cytoplasmic localization of p27kip1 protein, a tumor suppressor, is related to chemotherapy resistance in CCA, and its underlying mechanism is unclear. This study found that UBE2I, a key enzyme for SUMOylation, was highly expressed in CCA tissues, leading to downregulation of p27kip1 and poorer outcomes. Silencing UBE2I inhibited CCA cell proliferation, delayed tumor growth in vivo, and increased sensitivity to chemotherapy, possibly due to cell cycle arrest induced by p27kip1 nuclear accumulation.
MOLECULAR CARCINOGENESIS
(2023)
Article
Multidisciplinary Sciences
Terry R. Suk, Marilyn T. Tirard, Zoe A. Fisk, Miso Mitkovski, Haley M. Geertsma, Jean-Louis A. Parmasad, Meghan M. Heer, Steve M. Callaghan, Fritz Benseler, Nils Brose, Marilyn Tirard, Maxime W. C. Rousseaux
Summary: SUMOylation is a protein modification widely present in evolutionarily conserved eukaryotes and has broad biological significance. To differentiate between SUMO paralogs and uncover their specific functions in vivo, His6-HA-Sumo2 and HA-Sumo2 knockin mouse lines were generated, expanding upon the existing His6-HA-Sumo1 mouse line. By utilizing the specificity of the HA epitope, regional differences in Sumo1 and Sumo2 expression were observed through whole-brain imaging. Immunoprecipitation coupled with mass spectrometry identified shared and specific neuronal targets of Sumo1 and Sumo2, and proximity ligation assays provided insight into the subcellular distribution of neuronal Sumo2-conjugates. These mouse models and associated datasets provide a powerful framework to determine the native SUMO code in cells of the central nervous system.
Review
Cell Biology
Quyen Thu Bui, Jeong Hee Hong, Minseok Kwak, Ji Yeon Lee, Peter Chang-Whan Lee
Summary: The ubiquitin-mediated degradation system controls various tumor-promoting processes through the sequential action of E1, E2, and E3 enzymes, with E2 enzymes playing a central role in modulating pathophysiological processes in the tumor microenvironment.
Article
Biochemistry & Molecular Biology
Muthukumar Elangovan, Jun Ka, Boryeong Pak, Woosoung Choi, Se-Ra Oh, Suk-Won Jin, Yung Joon Yoo
Summary: Ubiquitination plays an important regulatory role in angiogenesis, with E3 enzymes being extensively studied. The role of E2 enzymes in angiogenesis is less known. Through analysis of single-cell RNA sequencing data, UBE2V1 was identified as one of the most abundantly expressed E2s in endothelial cells. Inhibition of UBE2V1 affects endothelial cell proliferation, viability, morphogenesis, and migration, and is critical for FGF2-induced angiogenesis.
Article
Fisheries
Jian Zhang, Xiangyi Sun, Xuepeng Li, Shuning Zhang, Xiudan Xu, Jixing Feng
Summary: Many viruses hijack the host's ubiquitin-proteasome system (UPS) for successful infection. This study identified and characterized a protein called SmE2D2 in turbot, which interacts with the RBIV-C1 virus. The results show that SmE2D2 is an E2 ubiquitin-conjugating enzyme that is used by RBIV-C1 to promote efficient replication.
Article
Biochemistry & Molecular Biology
Fumiyo Ikeda
Summary: The ubiquitin-proteasomal system and the autophagy-lysosome system are two major degradation systems in mammalian cells. Ubiquitin not only regulates proteasomal degradation of substrates but also regulates the autophagy pathway. Ubiquitin plays a key role in autophagy regulation by recruiting cargos to phagophore in a ubiquitin-dependent manner.
Article
Biochemistry & Molecular Biology
Kazuhide Miyamoto, Atsushi Matsumoto
Summary: In this study, the unique properties of ARFs in E2-binding and auto-ubiquitination were demonstrated in ubiquitination assays. Point mutations of ARF by tryptophan resulted in changes in E2 specificity and Ub chain elongation. ARF mutants interacted with all 11 E2s and promoted auto-ubiquitination, allowing specific detection of E2 activities during ubiquitination.
Article
Plant Sciences
Pengcheng Wang, Kai Guo, Qian Su, Jinwu Deng, Xianlong Zhang, Lili Tu
Summary: The E2 enzyme GhUBC2L modulates histone monoubiquitination synergistically with E3 ligase GhUbox8 to control organ size in cotton by affecting the expression of genes related to cell cycle and organ development.
Article
Immunology
Jaime Larraga, Pedro J. Alcolea, Ana M. Alonso, Luis T. C. Martins, Inmaculada Moreno, Mercedes Dominguez, Vicente Larraga
Summary: Leishmania parasites cause significant morbidity and mortality in many developing countries. Researchers have identified a vaccine candidate, LiUBC1, which shows partial protection against L. infantum infection in a Syrian hamster model.
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
Genetics & Heredity
Fengchao Zhang, Yao Chen, Jie Shen, Junzheng Zhang
Summary: The Notch signaling pathway plays crucial roles in animal development, with protein ubiquitination regulating the stability and activity of major signaling components. Multiple ubiquitin ligases and deubiquitinating enzymes have been identified in Drosophila that modify Notch ligand and receptor proteins. UbcD1 has been found to be required for Notch signaling activation during Drosophila wing development, suggesting a novel role for UbcD1 in development.
FRONTIERS IN GENETICS
(2021)
Article
Chemistry, Multidisciplinary
Lu-Jun Liang, Guo-Chao Chu, Qian Qu, Chong Zuo, Junxiong Mao, Qingyun Zheng, Jingnan Chen, Xianbin Meng, Yangwode Jing, Haiteng Deng, Yi-Ming Li, Lei Liu
Summary: This study describes a new total chemical synthesis approach for constructing a structurally new activity-based E2-Ub probe, which covalently captures the catalytic site of Cys-dependent E3 ligases. Chemical cross-linking coupled with mass spectrometry demonstrated the utility of this new probe in structural analysis of intermediates formed during thiol transfer processes. The study exemplifies the utility of chemical protein synthesis in developing protein probes for biological studies.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Food Science & Technology
Xin-Yi Nie, Yang Xue, Ling Li, Zhixin Jiang, Bei Qin, Yu Wang, Shihua Wang
Summary: The importance and mechanism of SUMOylation in the saprophytic fungus Aspergillus flavus were investigated, revealing its role in fungal biology and potential for controlling food contamination.
INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Sachio Tsuchida, Tomohiro Nakayama
Summary: Oral health is crucial for overall well-being and may indicate systemic diseases, with the ubiquitin system playing a role in cellular functions and DNA repair. Deubiquitinating enzymes are essential regulators of ubiquitination-mediated degradation and have significant impacts on cellular pathways and biological processes. Research highlights the relationship between ubiquitination, deubiquitination, and oral diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Derek L. Bolhuis, Raquel C. Martinez-Chacin, Kaeli A. Welsh, Tatyana Bodrug, Liying Cui, Michael J. Emanuele, Nicholas G. Brown
Summary: The proper degradation of proteins by the ubiquitin-proteasome system is crucial for the accurate progression of the cell cycle, and the activity of ubiquitin ligases is tightly regulated. This study investigated the role of the Anaphase-Promoting Complex/Cyclosome (APC/C) in mitotic progression and G1 maintenance, and discovered the involvement of EMI1 in regulating APC/C activity during G1. Additionally, it was found that a C-terminal peptide fragment of EMI1 can activate the priming of specific substrates by the APC/C.
Review
Gastroenterology & Hepatology
Joseph C. Ahn, Pai-Chi Teng, Pin-Jung Chen, Edwin Posadas, Hsian-Rong Tseng, Shelly C. Lu, Ju Dong Yang
Summary: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related morbidity and mortality worldwide, and current tests like alpha-fetoprotein have limited accuracy. Liver biopsy, while informative, is not routinely used due to invasiveness, leading to a need for new biomarkers. Liquid biopsy, specifically detection of circulating tumor cells (CTCs), offers potential for early detection and personalized treatment management in HCC patients. Quantitative analysis of CTCs can predict disease prognosis and treatment response, highlighting the importance of developing CTC detection platforms for clinical use.
Article
Gastroenterology & Hepatology
Marcos F. Fondevila, Uxia Fernandez, Maria J. Gonzalez-Rellan, Natalia Da Silva Lima, Xabier Buque, Agueda Gonzalez-Rodriguez, Cristina Alonso, Marta Iruarrizaga-Lejarreta, Teresa C. Delgado, Marta Varela-Rey, Ana Senra, Vera Garcia-Outeiral, Eva Novoa, Cristina Iglesias, Begona Porteiro, Daniel Beiroa, Cintia Folgueira, Marta Tojo, Jorge L. Torres, Lourdes Hernandez-Cosido, Oscar Blanco, Juan Pablo Arab, Francisco Barrera, Diana Guallar, Miguel Fidalgo, Miguel Lopez, Carlos Dieguez, Miguel Marcos, Maria L. Martinez-Chantar, Marco Arrese, Carmelo Garcia-Monzon, Jose M. Mato, Patricia Aspichueta, Ruben Nogueiras
Summary: The LPI/GPR55 system activates ACC to affect lipid metabolism, playing a role in the development of NAFLD and NASH. Inhibition of GPR55 and ACCα can block the effects of LPI, which may be a potential new strategy for treating NAFLD and NASH.
Article
Gastroenterology & Hepatology
Ganeko Bernardo-Seisdedos, Jon Bilbao, David Fernandez-Ramos, Fernando Lopitz-Otsoa, Virginia Gutierrez de Juan, Maider Bizkarguenaga, Borja Mateos, Marcos F. Fondevila, Jordi Abril-Fornaguera, Tammo Diercks, Shelly C. Lu, Ruben Nogueiras, Jose M. Mato, Oscar Millet
Summary: The study develops a P-31 NMR-based method to study liver phosphorome, identifying and quantifying phosphorylated metabolites. By applying this technique to different disease models, the study identifies alterations in metabolic pathways, correlations with histological features, and the impact of drug treatment on liver metabolism.
Article
Multidisciplinary Sciences
Qinglan Wang, So Yeon Kim, Hiroshi Matsushita, Zhijun Wang, Vijay Pandyarajan, Michitaka Matsuda, Koichiro Ohashi, Takashi Tsuchiya, Yoon Seok Roh, Calvin Kiani, Yutong Zhao, Michael Chan, Suzanne Devkota, Shelly C. Lu, Tomoko Hayashi, Dennis A. Carson, Ekihiro Seki
Summary: TLR7 signaling has a protective effect in the AH mouse model, and the TLR7 agonistic agent 1Z1 holds therapeutic potential for the treatment of ALD. Oral administration of 1Z1 prevents intestinal barrier disruption and bacterial translocation, suppressing ethanol-induced hepatic injury, steatosis, and inflammation. 1Z1 treatment also up-regulates the expression of antimicrobial peptides and intestinal IL-22, modulating the microbiome composition and playing a protective role in the AH mouse model.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Jon Gil-Martinez, Iratxe Macias, Luca Unione, Ganeko Bernardo-Seisdedos, Fernando Lopitz-Otsoa, David Fernandez-Ramos, Ana Lain, Arantza Sanz-Parra, Jose M. Mato, Oscar Millet
Summary: Hereditary tyrosinemia type I is a severe genetic disorder that can lead to death if left untreated. Currently, the only available treatment involves a low tyrosine diet combined with the herbicidal nitisinone, but this approach is not without side effects and long-term complications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Leire Egia-Mendikute, Alexandre Bosch, Endika Prieto-Fernandez, So Young Lee, Borja Jimenez-Lasheras, Ana Garcia del Rio, Asier Antonana-Vildosola, Chiara Bruzzone, Maider Bizkarguenaga, Nieves Embade, Ruben Gil-Redondo, Maria Luz Martinez-Chantar, Marcos Lopez-Hoyos, Nicola G. A. Abrescia, Jose M. Mato, Oscar Millet, Asis Palazon
Summary: Egia-Mendikute et al. have developed a multiplexed flow cytometric bead array to detect antibodies reactive to three immunogenic SARS-CoV-2 proteins simultaneously. This assay is more sensitive than ELISA and has superior potential to detect low antibody titers, even in COVID-19-negative individuals.
COMMUNICATIONS BIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Chiara Bruzzone, Ruben Gil-Redondo, Marisa Seco, Rocio Barragan, Laura de la Cruz, Claire Cannet, Hartmut Schaefer, Fang Fang, Tammo Diercks, Maider Bizkarguenaga, Beatriz Gonzalez-Valle, Ana Lain, Arantza Sanz-Parra, Oscar Coltell, Ander Lopez de Letona, Manfred Spraul, Shelly C. Lu, Elisabetta Buguianesi, Nieves Embade, Quentin M. Anstee, Dolores Corella, Jose M. Mato, Oscar Millet
Summary: Metabolic syndrome (MetS) is a complex condition without a clear medical definition. This study used NMR metabolomics to analyze urine samples from a European cohort, revealing a unique molecular signature of MetS. The results showed that MetS progression is associated with specific changes in the urine metabolome, which can be used to identify individuals with MetS and provide insight into the transitional states between healthy individuals and MetS patients.
CARDIOVASCULAR DIABETOLOGY
(2021)
Article
Gastroenterology & Hepatology
Komal Ramani, Aaron E. Robinson, Joshua Berlind, Wei Fan, Aushinie Abeynayake, Aleksandra Binek, Lucia Barbier-Torres, Mazen Noureddin, Nicholas N. Nissen, Zehra Yildirim, Ebru Erbay, Jose M. Mato, Jennifer E. Van Eyk, Shelly C. Lu
Summary: Our study identified a SAMe-sensitive mechanism of LARP1 phosphorylation that may be involved in the progression from NASH to HCC.
Article
Chemistry, Analytical
Philipp Nitschke, Samantha Lodge, Torben Kimhofer, Reika Masuda, Sze-How Bong, Drew Hall, Hartmut Schaefer, Manfred Spraul, Nils Pompe, Tammo Diercks, Ganeko Bernardo-Seisdedos, Jose M. Mato, Oscar Millet, Daniella Susic, Amanda Henry, Emad M. El-Omar, Elaine Holmes, John C. Lindon, Jeremy K. Nicholson, Julien Wist
Summary: This study presents a J-Edited Diffusional (JEDI) proton NMR spectroscopic approach that selectively enhances signals from inflammatory markers in blood serum. The results show that JEDI is an improved method for selectively investigating inflammatory signals in serum and may have widespread diagnostic applicability to disease states associated with systemic inflammation.
ANALYTICAL CHEMISTRY
(2022)
Article
Biophysics
Maider Bizkarguenaga, Chiara Bruzzone, Ruben Gil-Redondo, Itxaso SanJuan, Itziar Martin-Ruiz, Diego Barriales, Ainhoa Palacios, Samuel T. Pasco, Beatriz Gonzalez-Valle, Ana Lain, Lara Herrera, Aida Azkarate, Miguel Angel Vesga, Cristina Eguizabal, Juan Anguita, Nieves Embade, Jose M. Mato, Oscar Millet
Summary: COVID-19 is a systemic infectious disease that affects multiple organs, with half of the patients showing abnormal metabolism six months after infection. Most patients are asymptomatic or have mild symptoms, possibly reflecting the metabolic response to immune stress.
NMR IN BIOMEDICINE
(2022)
Article
Multidisciplinary Sciences
Lucia Barbier-Torres, Ben Murray, Jin Won Yang, Jiaohong Wang, Michitaka Matsuda, Aaron Robinson, Aleksandra Binek, Wei Fan, David Fernandez-Ramos, Fernando Lopitz-Otsoa, Maria Luque-Urbano, Oscar Millet, Nirmala Mavila, Hui Peng, Komal Ramani, Roberta Gottlieb, Zhaoli Sun, Suthat Liangpunsakul, Ekihiro Seki, Jennifer E. Van Eyk, Jose M. Mato, Shelly C. Lu
Summary: MAT alpha 1 plays a role in reducing activity and causing mitochondrial dysfunction in alcohol-associated liver disease (ALD). This study found that the peptidyl-prolyl cis/trans isomerase PIN1 and kinase CK2 mediate the selective depletion of mitochondrial MAT alpha 1 in ALD. Blocking the interaction between PIN1 and MAT alpha 1 increased mitochondrial levels of MAT alpha 1 and protected against alcohol-induced mitochondrial dysfunction and fat accumulation.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Analytical
Reika Masuda, Samantha Lodge, Luke Whiley, Nicola Gray, Nathan Lawler, Philipp Nitschke, Sze-How Bong, Torben Kimhofer, Ruey Leng Loo, Berin Boughton, Annie X. Zeng, Drew Hall, Hartmut Schaefer, Manfred Spraul, Girish Dwivedi, Bu B. Yeap, Tammo Diercks, Ganeko Bernardo-Seisdedos, Jose M. Mato, John C. Lindon, Elaine Holmes, Oscar Millet, Julien Wist, Jeremy K. Nicholson
Summary: SARS-CoV-2 infection leads to a decrease in lipoprotein-bound serum phospholipids, resulting in supra-molecular phospholipid composite (SPC) signals detected in diffusion and relaxation edited H-1 NMR spectra. This study utilized Statistical HeterospectroscoY in n-dimensions (SHYn) approach to identify the major phospholipid components contributing to the SPC signals and correlated them with lipoprotein and lipid measurements. The SPC3/SPC2 ratio was strongly correlated with the apolipoprotein B100/A1 ratio, indicating the potential of serum SPC measurement as a metric of cardiovascular risk based on a single NMR experiment.
ANALYTICAL CHEMISTRY
(2022)
Article
Gastroenterology & Hepatology
Ibon Martinez-Arranz, Chiara Bruzzone, Mazen Noureddin, Ruben Gil-Redondo, Itziar Minchole, Maider Bizkarguenaga, Enara Arretxe, Marta Iruarrizaga-Lejarreta, David Fernandez-Ramos, Fernando Lopitz-Otsoa, Rebeca Mayo, Nieves Embade, Elizabeth Newberry, Bettina Mittendorf, Laura Izquierdo-Sanchez, Vaclav Smid, Jorge Arnold, Paula Iruzubieta, Ylenia Perez Castano, Marcin Krawczyk, Urko M. Marigorta, Martine C. Morrison, Robert Kleemann, Antonio Martin-Duce, Liat Hayardeny, Libor Vitek, Radan Bruha, Rocio Aller de la Fuente, Javier Crespo, Manuel Romero-Gomez, Jesus M. Banales, Marco Arrese, Kenneth Cusi, Elisabetta Bugianesi, Samuel Klein, Shelly C. Lu, Quentin M. Anstee, Oscar Millet, Nicholas O. Davidson, Cristina Alonso, Jose M. Mato
Summary: This study identified three metabolic subtypes of NAFLD, which are associated with cardiovascular disease and genetic risk factors. Despite similar rates of NASH and fibrosis among the subtypes, differences were observed in liver enzymes and lipid metabolism. Additionally, subtype A showed a lower risk of cardiovascular disease and genetic markers for NAFLD.
Article
Oncology
Amaia Zabala-Letona, Amaia Arruabarrena-Aristorena, Sonia Fernandez-Ruiz, Cristina Viera, Onintza Carlevaris, Amaia Ercilla, Isabel Mendizabal, Teresa Martin, Alice Macchia, Laura Camacho, Mikel Pujana-Vaquerizo, Pilar Sanchez-Mosquera, Veronica Torrano, Natalia Martin-Martin, Patricia Zuniga-Garcia, Mireia Castillo-Martin, Aitziber Ugalde-Olano, Ana Loizaga-Iriarte, Miguel Unda, Jose M. Mato, Edurne Berra, Maria L. Martinez-Chantar, Arkaitz Carracedo
Summary: This study investigates the regulation and function of Glycine N-Methyltransferase (GNMT) in prostate cancer and discovers that the enzyme is repressed when the oncogenic PI3K pathway is activated, adding complexity to its dependency on androgen signaling. Additionally, the study demonstrates the requirement of GNMT expression for the onset of invasive prostate cancer in a genetic mouse model.
Article
Biochemistry & Molecular Biology
Ruben Gil-Redondo, Ricardo Conde, Maider Bizkarguenaga, Chiara Bruzzone, Ana Lain, Beatriz Gonzalez-Valle, Milagros Iriberri, Carlos Ramos-Acosta, Eduardo Anguita, Juan Ignacio Arriaga Lariz, Pedro Pablo Espana Yandiola, Miguel Angel Moran, Mario Ernesto Jimenez-Mercado, Leire Egia-Mendikute, Maria Luisa Seco, Hartmut Schaefer, Claire Cannet, Manfred Spraul, Asis Palazon, Nieves Embade, Shelly C. Lu, Julien Wist, Jeremy K. Nicholson, Jose M. Mato, Oscar Millet
Summary: This study investigated the natural history of COVID-19 disease at the molecular level and characterized the metabolic and immunological phenoreversion in hospitalized severe patients and non-hospitalized recovered patients. The findings suggest that acute patients experience metabolic and immunological dysregulation, resulting in a slower recovery time, while non-hospitalized recovered patients do not show any associated metabolic or immune alterations.