Review
Biochemistry & Molecular Biology
Debdeep Dutta, Vartika Sharma, Mousumi Mutsuddi, Ashim Mukherjee
Summary: Notch signaling is an evolutionarily conserved pathway widely used for multiple cellular events during development. The pathway is tightly regulated by physical and biochemical modifications of the Notch receptor and its ligand, as well as through the process of ubiquitination carried out by E3 ubiquitin ligases to maintain proper signaling outcomes. Dysregulation of ubiquitination in Notch signaling can lead to abnormal signaling and contribute to various human diseases.
Article
Virology
Lei Hou, Xiaohan Hu, Jinshuo Guo, Rong Quan, Li Wei, Jing Wang, Jiangwei Song, Jue Liu
Summary: In this study, we found that aMPV/C infection induces MAVS degradation through the ubiquitin-proteasome pathway at the post-translational level. Furthermore, specific amino acid sites were identified as pivotal in the formation of polyubiquitin chains during MAVS degradation. E3 ubiquitin ligases targeting MAVS were also identified, with RNF5 shown to be involved in MAVS degradation in aMPV/C-infected cells.
Article
Biochemistry & Molecular Biology
Busra Turgu, Amal El-Naggar, Melanie Kogler, Luigi Tortola, Hai-Feng Zhang, Mariam Hassan, Michael M. Lizardo, Sonia H. Y. Kung, Wan Lam, Josef M. Penninger, Poul H. Sorensen
Summary: HACE1 destabilizes mTOR by targeting RAC1 within mTOR-associated complexes, leading to decreased mTORC1 and mTORC2 activity. HACE1 deficiency results in enhanced mTORC1/2 activity, which can be reversed by inhibiting RAC1. These findings reveal a unique ubiquitin-dependent process to control the activity of mTOR signaling complexes.
Article
Genetics & Heredity
Hongbiao Ran, Chunyan Li, Ming Zhang, Jincheng Zhong, Hui Wang
Summary: Ubiquitination, a post-transcriptional modification, plays a crucial role in protein degradation and is involved in various physiological and pathological processes, including animal adipogenesis. The E3 ligases have been found to regulate adipogenesis, but their role in the recognition and connection between substrate and ubiquitin during ubiquitination has been overlooked. This review summarizes the regulatory and modification targets of E3 ligases in animal adipogenesis, explains the regulatory mechanisms in lipogenic pathways, and analyzes existing positive results, providing valuable research directions for further understanding the regulatory mechanisms of E3 ligases in animal adipogenesis.
Article
Biochemistry & Molecular Biology
Seung-Heon Baek, Yeun-Kyu Jang
Summary: AMBRA1 negatively regulates ALDH1B1 through noncanonical ubiquitination, mediated by cooperation with E3 ligases like TRAF6. It controls the K27- and K33-linked ubiquitination of ALDH1B1, impacting its expression and self-association ability.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Alberto Coego, Jose Julian, Jorge Lozano-Juste, Gaston A. Pizzio, Abdulwahed F. Alrefaei, Pedro L. Rodriguez
Summary: Post-translational modifications, particularly protein ubiquitylation, play a crucial role in regulating protein function and stability in various aspects of plant biology. Ubiquitin code not only targets substrates for proteolytic degradation but also regulates protein interactions, activity, and localization through nonproteolytic functions. This review focuses on the ubiquitylation of ABA receptors and PP2C coreceptors, as well as other post-translational modifications of ABA receptors that lead to their ubiquitination and degradation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Albano Toska, Nikita Modi, Lin-Feng Chen
Summary: RUNX3 is a transcription factor involved in cell proliferation and development. It can act both as a tumor suppressor and an oncogene in different cancers. The tumor suppressor function of RUNX3 is mainly attributed to its ability to suppress cancer cell proliferation through ubiquitination and proteasomal degradation, while it can also be inactivated through the same mechanism.
Article
Biochemical Research Methods
Brian D. Young, Jihui Sha, Ajay A. Vashisht, James A. Wohlschlegel
Summary: This study identified novel regulators of G beta gamma signaling in human cells using mass spectrometry, with KCTD2 and KCTD5 shown to specifically recognize G beta gamma and be involved in downstream signal transduction. These KCTD proteins act as substrate adaptors for a multisubunit CUL3-RING ubiquitin ligase, promoting monoubiquitination of G beta(1/2) lysine-23 and regulating downstream signaling. Depletion of these adaptors impairs downstream signaling in cancer cell lines.
JOURNAL OF PROTEOME RESEARCH
(2021)
Review
Cell Biology
Emanuela Senatore, Rosa Iannucci, Francesco Chiuso, Rossella Delle Donne, Laura Rinaldi, Antonio Feliciello
Summary: Primary cilia are microtubule-based sensory organelles that receive and transmit external signals to control cell growth, differentiation, and development. The formation and disassembly of primary cilia are finely regulated during the cell cycle. The ubiquitin-proteasome system and autophagy machinery play essential roles in cilia dynamics.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Peng Jiang, Lejiao Ren, Li Zhi, Zhong Yu, Fengxiang Lv, Fengli Xu, Wei Peng, Xiaoyu Bai, Kunlun Cheng, Li Quan, Xiuqin Zhang, Xianhua Wang, Yan Zhang, Dan Yang, Xinli Hu, Rui-Ping Xiao
Summary: High glucose suppresses AMPK signaling through MG53-mediated AMPK alpha degradation and deactivation, as well as ROS-dependent inhibition of AMPK alpha phosphorylation at T172. These findings elucidate the mechanism of impaired AMPK signaling in overnutrition-related diseases and underscore the importance of maintaining the yin-yang balance of AMPK signaling for metabolic homeostasis.
Article
Biochemistry & Molecular Biology
Wenjuan Yu, Ramesh Singh, Zhao Wang, Bert W. O'Malley, Ping Yi
Summary: TRAF4-mediated ubiquitination of IRS-1 is physiologically relevant and crucial for IGF signal transduction, as it promotes an atypical K29-linked ubiquitination at the C-terminal end of IRS-1, affecting downstream AKT and ERK phosphorylation and breast cancer cell proliferation. The nonproteolytic ubiquitination of IRS-1 is a key step in conveying IGF-1 stimulation from IGFR to IRS-1.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
KyoungJoo Cho, Sejeong Kim, Seung Ho Choi
Summary: SOCS2 is upregulated in Huntington's disease and substantially induced in extended polyglutamine-expressing striatal cells. The induced level is augmented under aging conditions. In extended polyglutamine-expressing cells, downregulated SOCS2 improves autophagic dysfunction rather than altered inflammatory conditions.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Yi Zheng, Jian Deng, Lulu Han, Meng-Wei Zhuang, Yanwen Xu, Jing Zhang, Mei-Ling Nan, Yang Xiao, Peng Zhan, Xinyong Liu, Chengjiang Gao, Pei-Hui Wang
Summary: This study reveals the involvement of the stress response pathway and innate antiviral immunity in the pathogenic mechanism of SARS-CoV-2. NSP5 and N protein of SARS-CoV-2 were found to attenuate the formation of antiviral stress granules (avSG). NSP5 suppressed avSG formation and disrupted the RIG-I-MAVS complex to weaken the RIG-I-mediated antiviral response, while N protein specifically targeted cofactors upstream of RIG-I and affected the recognition of dsRNA by RIG-I.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Review
Immunology
Luiz Pedro Souza-Costa, Josiane Teixeira Andrade-Chaves, Juvana Moreira Andrade, Vivian Vasconcelos Costa, Luis Henrique Franco
Summary: Innate immunity is the body's first line of defense against infections, but uncontrolled or aberrant inflammatory responses can lead to tissue damage and chronic inflammatory diseases. This review focuses on the importance of ubiquitination in regulating innate immune signaling and inflammation, highlighting the role of the protein Smurf1 and its potential as a therapeutic target for infectious and inflammatory conditions.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Microbiology
Xing Yang, Zhijuan Hu, Jingjie Yuan, Run Zou, Yilan Wang, Xuan Peng, Shan Xu, Chengjian Xie
Summary: Two ubiquitin ligase E3 genes (VdBre1 and VdHrd1) in Verticillium dahliae are intrinsically associated with virulence, and their deletion significantly impairs the ability of the fungus to colonize plants and form penetration pegs. VdBre1 governs the lipid metabolism pathway, while VdHrd1 participates in endoplasmic-reticulum-related processes. The Delta VdBre1 mutant shows a significant decrease in histone ubiquitination and histone H3K4 trimethylation levels.
Article
Immunology
Cynthia Louis, Fernando Souza-Fonseca-Guimaraes, Yuyan Yang, Damian D'Silva, Tobias Kratina, Laura Dagley, Soroor Hediyeh-Zadeh, Jai Rautela, Seth Lucian Masters, Melissa J. Davis, Jeffrey J. Babon, Bogoljub Ciric, Eric Vivier, Warren S. Alexander, Nicholas D. Huntington, Ian P. Wicks
JOURNAL OF EXPERIMENTAL MEDICINE
(2020)
Article
Immunology
Mary Speir, Cameron J. Nowell, Alyce A. Chen, Joanne A. O'Donnell, Isaac S. Shamie, Paul R. Lakin, Akshay A. D'Cruz, Roman O. Braun, Jeff J. Babon, Rowena S. Lewis, Meghan Bliss-Moreau, Inbar Shlomovitz, Shu Wang, Louise H. Cengia, Anca I. Stoica, Razq Hakem, Michelle A. Kelliher, Lorraine A. O'Reilly, Heather Patsiouras, Kate E. Lawlor, Edie Weller, Nathan E. Lewis, Andrew W. Roberts, Motti Gerlic, Ben A. Croker
Correction
Immunology
Cynthia Louis, Fernando Guimaraes, Yuyan Yang, Damian D'Silva, Tobias Kratina, Laura Dagley, Soroor Hediyeh-Zadeh, Jai Rautela, Seth Lucian Masters, Melissa J. Davis, Jeffrey J. Babon, Bogoljub Ciric, Eric Vivier, Warren S. Alexander, Nicholas D. Huntington, Ian P. Wicks
JOURNAL OF EXPERIMENTAL MEDICINE
(2020)
Article
Chemistry, Multidisciplinary
Thomas G. Meikle, David W. Keizer, Jeffrey J. Babon, Calum J. Drummond, Frances Separovic, Charlotte E. Conn, Shenggen Yao
Review
Hematology
David M. Ross, Jeffrey J. Babon, Denis Tvorogov, Daniel Thomas
Summary: Activation of JAK-STAT signaling is a hallmark of myelofibrosis, with JAK2 inhibitor treatment leading to a phenomenon called "persistence" that does not significantly impact the abnormal hematopoietic clone compared to usual resistance patterns.
Article
Chemistry, Physical
Thomas G. Meikle, David W. Keizer, Jeffrey J. Babon, Calum J. Drummond, Frances Separovic, Charlotte E. Conn, Shenggen Yao
Summary: Proton transportation and chemical exchange near the lipid bilayer membrane surface are key in various applications, especially involving cellular energy turnover and transmembrane mobility. The unique structure of lipidic inverse bicontinuous cubic phases (LCPs) plays a crucial role in these processes, with potential for chemical exchange studies using techniques like PFG-NMR and ID EXSY. This study provides insights into the chemical exchange between lipids and water in LCPs, offering valuable information on hydration levels and exchange rate constants.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Biochemical Research Methods
Jarrod J. Sandow, Andrew I. Webb, Dina Stockwell, Nadia J. Kershaw, Cyrus Tan, Satoshi Ishido, Warren S. Alexander, Douglas J. Hilton, Jeffrey J. Babon, Nicos A. Nicola
Summary: Research showed that MARCH proteins regulate the expression of immune response-related receptors and affect various cell surface proteins, including integrin complexes crucial for immune cell homing, adhesion, and migration.
Article
Biochemistry & Molecular Biology
Lung-Yu Liang, Michael Roy, Christopher R. Horne, Jarrod J. Sandow, Minglyanna Surudoi, Laura F. Dagley, Samuel N. Young, Toby Dite, Jeffrey J. Babon, Peter W. Janes, Onisha Patel, James M. Murphy, Isabelle S. Lucet
Summary: EphB6 and EphA10, classified as pseudokinase members of the Eph receptor family, play crucial roles in contact-dependent cell-cell communication by transmitting extracellular signals into intracellular cues. Despite their deregulation being strongly linked to proliferative diseases, their catalytically dead nature raises questions about how non-catalytic functions contribute to Eph receptor signaling homeostasis. This study characterized the biochemical properties and topology of their intracellular regions, revealing high flexibility and interactions between component domains, offering potential for pharmacological targeting against oncogenic signaling through ATP binding capabilities.
BIOCHEMICAL JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Hao Chen, Yuntong Wu, Kunlun Li, Iain Currie, Narelle Keating, Farhad Dehkhoda, Christoph Grohmann, Jeffrey J. Babon, Sandra E. Nicholson, Brad E. Sleebs
Summary: Suppressor of cytokine signaling 1 (SOCS1) has been identified as a potential therapeutic target for inflammatory and viral diseases. This study successfully identified specific phosphotyrosine peptides that have high affinity and selectivity for the SH2 domain of SOCS1. These findings provide insights for the development of cell-permeable peptidomimetics targeting the SOCS1-SH2 domain for the treatment of inflammatory and viral diseases.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Rhiannon Morris, Douglas J. Hilton, Andrew Jarratt, Jeffrey J. Babon
Summary: Interleukin 6, a pleiotropic cytokine, plays a critical role in immune responses, inflammation, and haematopoiesis by triggering activation of the JAK/STAT signaling cascade in cells. Studies utilizing the M1 cell line have contributed to our understanding of the molecular mechanisms governing IL-6 signaling.
Article
Multidisciplinary Sciences
Rhiannon Morris, Yaoyuan Zhang, Julia Ellyard, Carola G. Vinuesa, James M. Murphy, Artem Laktyushin, Nadia J. Kershaw, Jeffrey J. Babon
Summary: The researchers presented structures of the substrate recognition (SH2) domain of LNK in complex with phosphorylated motifs from JAK2 and EPOR, providing insight into its binding specificity and mode of action.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Edmond M. Linossi, Kunlun Li, Gianluca Veggiani, Cyrus Tan, Farhad Dehkhoda, Colin Hockings, Dale J. Calleja, Narelle Keating, Rebecca Feltham, Andrew J. Brooks, Shawn S. Li, Sachdev S. Sidhu, Jeffrey J. Babon, Nadia J. Kershaw, Sandra E. Nicholson
Summary: The researchers identified an exosite on the SOCS2-SH2 domain that can enhance the affinity of SOCS2 for phosphorylated targets by binding a non-phosphorylated peptide, leading to increased inhibition of growth hormone signaling.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Rhiannon Morris, Liesl Butler, Andrew Perkins, Nadia J. Kershaw, Jeffrey J. Babon
Summary: LNK is an adaptor protein that regulates cytokine signaling and constrains the activation of the JAK-STAT pathway. Mutations in LNK can lead to increased signaling and contribute to various hematological and inflammatory diseases.
Review
Biophysics
Shenggen Yao, David W. Keizer, Jeffrey J. Babon, Frances Separovic
Summary: Nuclear magnetic resonance (NMR) is a well-established method for characterizing protein structure, dynamics, and interactions, while also providing insights into molecular translational and rotational motion. These aspects play a crucial role in assessing changes in protein oligomeric state in solution.
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2022)
Article
Multidisciplinary Sciences
Shuwei Liang, Eric Tran, Xin Du, Jiajun Dong, Harrison Sudholz, Hao Chen, Zihan Qu, Nicholas D. Huntington, Jeffrey J. Babon, Nadia J. Kershaw, Zhong-Yin Zhang, Jonathan B. Baell, Florian Wiede, Tony Tiganis
Summary: In this study, the authors demonstrate that inhibition of PTP1B and PTPN2 in tumor cells and T cells with a small molecule inhibitor represses the growth of immunogenic and cold tumors, and enhances response to anti-PD-1 immunotherapy without promoting immune-related toxicities.
NATURE COMMUNICATIONS
(2023)