Review
Cell Biology
Jara Lascorz, Joan Codina-Fabra, David Reverter, Jordi Torres-Rosell
Summary: Post-translational modification by SUMO proteins involves non-covalent interactions with other proteins, which play crucial roles in regulating protein activity, localization, and stability.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Jie Li, Gregory J. Krause, Qi Gui, Susmita Kaushik, Gergely Rona, Qingyue Zhang, Feng-Xia Liang, Avantika Dhabaria, Carlos Anerillas, Jennifer L. Martindale, Nikita Vasilyev, Manor Askenazi, Beatrix Ueberheide, Evgeny Nudler, Myriam Gorospe, Ana Maria Cuervo, Michele Pagano
Summary: This study identifies a new function for mammalian SKP1 in the endolysosomes, which is independent of its established role as a component of ubiquitin ligases. SKP1 is found to be phosphorylated under nutrient-poor conditions, promoting V-ATPase assembly and acidification of late endosomes for degradation. Under nutrient-rich conditions, phosphorylated SKP1 is SUMOylated and allows unconventional secretion through interaction with SEC22B.
Review
Biochemistry & Molecular Biology
Sara Martin-Villanueva, Gabriel Gutierrez, Dieter Kressler, Jesus de la Cruz
Summary: Ubiquitin is a highly conserved small protein in eukaryotes that functions as a post-translational modifier through ubiquitination. It plays a crucial role in ribosome biogenesis and function, along with other ubiquitin-like proteins such as SUMO. The fusion of ubiquitin moieties to specific ribosomal proteins is evolutionarily significant and helps regulate cellular processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Julio C. Y. Liu, Ulrike Kuhbacher, Nicolai B. Larsen, Nikoline Borgermann, Dimitriya H. Garvanska, Ivo A. Hendriks, Leena Ackermann, Peter Haahr, Irene Gallina, Claire Guerillon, Emma Branigan, Ronald T. Hay, Yoshiaki Azuma, Michael Lund Nielsen, Julien P. Duxin, Niels Mailand
Summary: The study reveals that the SUMO-targeted ubiquitin ligase RNF4 plays a major role in ubiquitylation and proteasomal clearance of SUMOylated DPCs in the absence of DNA replication. SUMO modifications of DPCs do not affect their rapid degradation during DNA replication, but provide a critical salvage mechanism to remove DPCs formed after replication. The absence of the SUMO-RNF4 pathway leads to accumulation of unresolved DPCs, causing defective chromosome segregation and cell death during mitosis.
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
Biochemistry & Molecular Biology
Shanshan Xu, Maria E. Gierisch, Anna Katharina Schellhaus, Ina Poser, Simon Alberti, Florian A. Salomons, Nico P. Dantuma
Summary: The absence of stress granules in cells has a negative impact on the functionality of the nuclear ubiquitin-proteasome system (UPS). Defective ribosome products (DRiPs) in stress granule-deficient cells accumulated at nucleoli instead of stress granules, accompanied by redistribution and enhanced degradation of SUMOylated proteins. Depletion of the SUMO-targeted ubiquitin ligase RNF4 restored the functionality of the nuclear UPS in stress granule-deficient cells. Stress granule-deficient cells showed increased formation of mutant ataxin-1 nuclear inclusions under thermal stress. These findings highlight the importance of stress granules in sequestering cytosolic misfolded proteins and preventing their accumulation in the nucleus.
Article
Multidisciplinary Sciences
Hyein G. Lee, Abigail A. Lemmon, Christopher D. Lima
Summary: The Ufd1/Npl4/Cdc48 complex enhances unfolding of substrates modified by SUMO-polyubiquitin hybrid chains through interactions with SUMO. It exhibits a stronger effect on substrates modified by these chains compared to polyubiquitin chains when given a choice. Cryo-EM structures reveal the interactions between Ufd1/Npl4/Cdc48 and ubiquitin during the unfolding process. These findings confirm the significance of SUMO and ubiquitin modifications in cellular functions and support a model where Ufd1/Npl4/Cdc48, SUMO, and ubiquitin conjugation pathways converge to promote clearance of proteins modified with SUMO and polyubiquitin.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biology
Arwa Raies, Ewa Tulodziecka, James Stainer, Lawrence Middleton, Ryan S. Dhindsa, Pamela Hill, Ola Engkvist, Andrew R. Harper, Slave Petrovski, Dimitrios Vitsios
Summary: In this study, a stochastic semi-supervised ML framework called DrugnomeAI was developed to estimate the druggability likelihood for every protein-coding gene in the human exome. The tool generates exome-wide predictions based on known drug targets and provides specialized models stratified by disease type or drug therapeutic modality. The results show enrichment of genes previously selected for clinical development programs, as well as genome-wide significance in phenome-wide association studies.
COMMUNICATIONS BIOLOGY
(2022)
Review
Microbiology
Gabriel Valiente
Summary: This article provides a systematic review of available virus-host protein-protein interaction database resources, evaluating their specificity, the number of interactions included, and functionality. It also analyzes the overlap of the databases and the structure of the interaction network across viruses and hosts.
FRONTIERS IN MICROBIOLOGY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Xiaodong Cheng
Summary: Protein SUMOylation is an essential post-translational modification for maintaining cellular homeostasis. Recent evidence suggests that liquid-liquid phase separation (LLPS)/ biomolecular condensates play a role in regulating cellular SUMOylation, providing insights into its cellular mechanism.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Cell Biology
Immacolata Giordano, Lucia Pirone, Veronica Muratore, Eukene Landaluze, Coralia Perez, Valerie Lang, Elisa Garde-Lapido, Monika Gonzalez-Lopez, Orhi Barroso-Gomila, Alfred C. O. Vertegaal, Ana M. Aransay, Jose Antonio Rodriguez, Manuel S. Rodriguez, James D. Sutherland, Rosa Barrio
Summary: The study investigates the interaction between two key transcription factors, CBX4 and SALL1, and reveals that increased SALL1 expression reduces the ubiquitination of CBX4, enhancing its stability. This leads to an increase in the number and size of CBX4-containing Polycomb bodies, resulting in greater repression of CBX4 target genes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Haodong Xu, Ruifeng Hu, Zhongming Zhao
Summary: This study constructed gene and mutation maps of degrons, revealing their evolutionary conservation, correlation with protein translational modification sites, association with cancer, and potential for drug resistance events.
MOLECULAR BIOLOGY AND EVOLUTION
(2023)
Article
Mathematical & Computational Biology
Yekai Zhou, Hongjun Chen, Sida Li, Ming Chen
Summary: The study focuses on databases with structural information of protein-protein interactions, developing a database extension called mPPI for PPI structural visualization. Compared to existing databases, mPPI can display target proteins and their multiple interactors simultaneously, aiding in multi-target drug discovery and protein macro-complex structure prediction.
DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION
(2021)
Article
Biochemistry & Molecular Biology
Audrey Dangoumau, Sylviane Marouillat, Roxane Coelho, Francois Wurmser, Celine Brulard, Shanez Haouari, Frederic Laumonnier, Philippe Corcia, Christian R. Andres, Helene Blasco, Patrick Vourc'h
Summary: Protein aggregates in motor neurons affected by ALS are associated with oxidative stress, which alters the expression of genes involved in ubiquitin and SUMO pathways. The combined effects of oxidative stress and ALS-related genetic mutations on gene expression highlight potential mechanisms underlying ALS pathophysiology and suggest targets for protecting motor neurons from neurodegeneration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemical Research Methods
Shayne D. Wierbowski, Siqi Liang, Yuan Liu, You Chen, Shagun Gupta, Nicole M. Andre, Steven M. Lipkin, Gary R. Whittaker, Haiyuan Yu
Summary: The emergence of new viral agents is driven by evolution of interactions between viral proteins and host targets, leading to increased infectivity of viruses such as SARS-CoV-2 through rapid evolution. State-of-the-art interface prediction and molecular docking were used to construct a three-dimensional structural interactome between SARS-CoV-2 and human, facilitating the study of how pathogen-host interactions impact transmission and virulence. The resource provided aims to aid in the development and testing of informed hypotheses for understanding the etiology and treatments of SARS-CoV-2.
Article
Oncology
Anne Van Arsdale, Nicole E. Patterson, Elaine C. Maggi, Lorenzo Agoni, Koenraad Van Doorslaer, Bryan Harmon, Nicole Neyadunsky, Dennis Y. S. Kuo, Mark H. Einstein, Jack Lenz, Cristina Montagna
GENES CHROMOSOMES & CANCER
(2020)
Article
Virology
Rafaela S. Fontenele, Andrew M. Salywon, Lucas C. Majure, Ilaria N. Cobb, Amulya Bhaskara, Jesus A. Avalos-Calleros, Gerardo R. Arguello-Astorga, Kara Schmidlin, Anthony Khalifeh, Kendal Smith, Joshua Schreck, Michael C. Lund, Matias Kohler, Martin F. Wojciechowski, Wendy C. Hodgson, Raul Puente-Martinez, Koenraad Van Doorslaer, Safaa Kumari, Christian Verniere, Denis Filloux, Philippe Roumagnac, Pierre Lefeuvre, Simone G. Ribeiro, Simona Kraberger, Darren P. Martin, Arvind Varsani
Article
Multidisciplinary Sciences
Guowei Yin, Jerry Zhang, Vinay Nair, Vinh Truong, Angelo Chaia, Johnny Petela, Joseph Harrison, Alemayehu A. Gorfe, Sharon L. Campbell
Article
Virology
Natalie Payne, Simona Kraberger, Rafaela S. Fontenele, Kara Schmidlin, Melissa H. Bergeman, Ivonne Cassaigne, Melanie Culver, Arvind Varsani, Koenraad Van Doorslaer
Article
Biochemistry & Molecular Biology
Joanna Liwocha, David T. Krist, Gerbrand J. van der Heden van Noort, Fynn M. Hansen, Vinh H. Truong, Ozge Karayel, Nicholas Purser, Daniel Houston, Nicole Burton, Mark J. Bostock, Michael Sattler, Matthias Mann, Joseph S. Harrison, Gary Kleiger, Huib Ovaa, Brenda A. Schulman
Summary: The study reveals that the aliphatic side chain specifying reactive amine geometry is a determinant of the ubiquitin code, affecting the assembly of ubiquitin chains by replacing the acceptor site.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Biochemical Research Methods
Henry Hieu M. Le, David Vang, Nadia Amer, Tou Vue, Colwin Yee, Hyam Kaou, Joseph S. Harrison, Nan Xiao, Joan Lin-Cereghino, Geoff P. Lin-Cereghino, Der Thor
PROTEIN EXPRESSION AND PURIFICATION
(2020)
Article
Biochemistry & Molecular Biology
Jennifer L. Franks, Raquel C. Martinez-Chacin, Xianxi Wang, Rochelle L. Tiedemann, Thomas Bonacci, Rajarshi Choudhury, Derek L. Bolhuis, Taylor P. Enrico, Ryan D. Mouery, Jeffrey S. Damrauer, Feng Yan, Joseph S. Harrison, M. Ben Major, Katherine A. Hoadley, Aussie Suzuki, Scott B. Rothbart, Nicholas G. Brown, Michael J. Emanuele
Article
Virology
Rafaela S. Fontenele, Andrew M. Salywon, Lucas C. Majure, Ilaria N. Cobb, Amulya Bhaskara, Jesus A. Avalos-Calleros, Gerardo R. Arguello-Astorga, Kara Schmidlin, Anthony Khalifeh, Kendal Smith, Joshua Schreck, Michael C. Lund, Matias Kohler, Martin F. Wojciechowski, Wendy C. Hodgson, Raul Puente-Martinez, Koenraad Van Doorslaer, Safaa Kumari, Kehinde A. Oyeniran, Christian Verniere, Denis Filloux, Philippe Roumagnac, Pierre Lefeuvre, Simone G. Ribeiro, Simona P. Kraberger, Darren P. Martin, Arvind Varsani
Summary: The diversity of geminiviruses infecting cacti is underestimated, with interspecies recombination and mixed infections being complex. Further investigation is needed to understand the threat posed by this complexity to cacti.
Article
Biochemistry & Molecular Biology
Kaeli A. Welsh, Derek L. Bolhuis, Anneroos E. Nederstigt, Joshua Boyer, Brenda R. S. Temple, Thomas Bonacci, Li Gu, Alban Ordureau, J. Wade Harper, Joshua P. Steimel, Qi Zhang, Michael J. Emanuele, Joseph S. Harrison, Nicholas G. Brown
Summary: Polyubiquitination mediated by E2 and E3 enzymes is essential for cell cycle control, epigenetic regulation, and development. The helix-turn-helix (HTH) motif of the UBC has been shown to regulate the intrinsic polyubiquitination activity in different E2s, with distinct functions observed in UBE2S and UBE2R2. The repurposing of the E2(HTH) motif in these proteins suggests a new mechanism for modulating ubiquitin transfer and highlights the potential for additional regulation in E2-E3-mediated polyubiquitination.
Article
Chemistry, Physical
Surya V. S. R. K. Pulavarti, Jack B. Maguire, Shirley Yuen, Joseph S. Harrison, Jermel Griffin, Lakshmanane Premkumar, Edward A. Esposito, George Makhatadze, Angel E. Garcia, Thomas M. Weiss, Edward H. Snell, Brian Kuhlman, Thomas Szyperski
Summary: Understanding protein folding is critical for protein sciences, and the study explores the interactions between water molecules and protein internal structures to understand the importance of cold unfolding. The results reveal a complex energy landscape for cold transitions, while the heat unfolded state is a random coil. The core disintegrates cooperatively during cold unfolding, maintaining a near-native helical content.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Multidisciplinary Sciences
Kellan P. Weston, Xiaoyi Gao, Jinghan Zhao, Kwang-Soo Kim, Susan E. Maloney, Jill Gotoff, Sumit Parikh, Yen-Chen Leu, Kuen-Phon Wu, Marwan Shinawi, Joshua P. Steimel, Joseph S. Harrison, Jason J. Yi
Summary: A large-scale assay was developed to characterize the functional valence of missense variants in the UBE3A gene, leading to the discovery that UBE3A hyperactivity increases the risk of neurodevelopmental disease.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Christopher J. Petell, Kathyrn Randene, Michael Pappas, Diego Sandoval, Brian D. Strahl, Joseph S. Harrison, Joshua P. Steimel
Summary: The METRIS assay leverages the concept of friction to measure protein-protein interaction affinities, offering high resolution and sensitivity. It allows for the measurement of a wide range of affinities with a small amount of reagents, providing new insights into epigenetic recognition.
Article
Multidisciplinary Sciences
Stephan T. Kudlacek, Stefan Metz, Devina Thiono, Alexander M. Payne, Thanh T. N. Phan, Shaomin Tian, Lawrence J. Forsberg, Jack Maguire, Ian Seim, Shu Zhang, Ashutosh Tripathy, Joseph Harrison, Nathan Nicely, Sandrine Soman, Michael K. McCracken, Gregory D. Gromowski, Richard G. Jarman, Lakshmanane Premkumar, Aravinda M. de Silva, Brian Kuhlman
Summary: By utilizing molecular modeling, researchers identified mutations in the DENV2 E protein that induce dimerization at low concentrations and enhance production yield. Antibodies targeting the stabilized dimers were found to elicit higher levels of DENV2-neutralizing antibodies compared to antibodies targeting WT E antigen. These findings demonstrate the potential of structure-based design for producing subunit vaccines for dengue and other flaviviruses.
Article
Microbiology
Kelly King, Brendan B. Larsen, Sophie Gryseels, Cecile Richet, Simona Kraberger, Robert Jackson, Michael Worobey, Joseph S. Harrison, Arvind Varsani, Koenraad Van Doorslaer
Summary: Papillomaviruses alter their nucleotide compositions to avoid detection by the innate immune system, specifically TLR9. This study provides evidence that TLR9 acts as a pattern recognition receptor during papillomavirus infection and demonstrates coevolution between papillomaviruses and their hosts. Additionally, cancer-associated human papillomaviruses show a reduction in CpG dinucleotides within a TLR9 recognition complex.
Article
Virology
Elizaveta T. Wick, Colton J. Treadway, Zhijun Li, Nathan Nicely, Zhizhong Ren, Albert S. Baldwin, Yue Xiong, Joseph S. Harrison, Nicholas G. Brown
Summary: Viruses evolve mechanisms to exploit cellular pathways that increase viral fitness, such as enhancing viral replication or evading the host cell immune response. This study reveals how viruses hijack the ubiquitin-proteosome system to target specific host proteins and optimize their binding affinity, allowing them to enhance viral replication and evade the host immune response.
JOURNAL OF VIROLOGY
(2022)
