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
Biochemistry & Molecular Biology
Matthew C. J. Yip, Samantha F. Sedor, Sichen Shao
Summary: This study reveals that ubiquitin binding and a cofactor, NAP1L1, regulate the selection of protein quality-control clients by the hybrid E2/E3 enzyme UBE2O. Attaching a single ubiquitin onto a client enhances UBE2O binding and multi-mono-ubiquitylation. UBE2O also repurposes the histone chaperone NAP1L1 as an adapter to recruit a subset of clients. Cryo-EM structures of human UBE2O in complex with NAP1L1 reveal a malleable client recruitment interface that is autoinhibited by the intrinsically reactive UBC domain. Adding a ubiquitylated client identifies a distinct ubiquitin-binding SH3-like domain required for client selection. Our findings highlight how multivalency and a feed-forward mechanism drive the selection of protein quality-control clients.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Yvan Campos, Amanda Nourse, Ajay Tanwar, Ravi Kalathur, Erik Bonten, Alessandra d'Azzo
Summary: CRL5(Ozz) is a muscle-specific ubiquitin ligase complex that plays a role in remodeling muscle structure by degrading specific substrates. In vitro assembly experiments showed that the reconstituted CRL5(Ozz) complex can interact with its substrates, indicating the production method used is suitable for generating functional CRL5(Ozz) in large quantities.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Katarzyna Retzer, Jeanette Moulinier-Anzola, Rebecca Lugsteiner, Nataliia Konstantinova, Maximilian Schwihla, Barbara Korbei, Christian Luschnig
Summary: Intracellular sorting and abundance of plasma membrane proteins are crucial for plants to sense and respond to environmental inputs. The reversible covalent modification by ubiquitin plays a key role in inducing adjustments in protein localization and functionality. The RING DOMAIN LIGASE family, including RGLG1, has been implicated in endocytic vacuolar cargo sorting, and this study provides evidence for their role in cargo trafficking between plasma membrane and endosomal compartments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Plant Sciences
Kun Wang, Shuai Fu, Liang Wu, Jianxiang Wu, Yaqin Wang, Yi Xu, Xueping Zhou
Summary: Our study discovered a conserved C4HC3-type E3 ligase, called microtubule-associated E3 ligase (MEL), that regulates broad-spectrum plant resistance against viral, fungal, and bacterial pathogens by degrading serine hydroxymethyltransferase (SHMT1) through the 26S proteasome pathway. We found that the NS3 protein encoded by rice stripe virus competitively binds to the MEL substrate recognition site, inhibiting MEL from interacting with and ubiquitinating SHMT1. This leads to the accumulation of SHMT1 and repression of downstream plant defence responses. Our findings provide insights into the ongoing arms race between pathogens and plants.
MOLECULAR PLANT PATHOLOGY
(2023)
Article
Neurosciences
Ribhav Mishra, Anurag Bansal, Amit Mishra
Summary: Ribosomes synthesize proteins according to cellular demands, but defects in the process can lead to non-functional proteins. Cells rely on quality control mechanisms like LISTERIN to eliminate abnormal proteins. LISTERIN's role in regulating protein quality is crucial for brain health and development, with implications for neurodegenerative diseases.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Daniel Horn-Ghetko, David T. Krist, J. Rajan Prabu, Kheewoong Baek, Monique P. C. Mulder, Maren Kluegel, Daniel C. Scott, Huib Ovaa, Gary Kleiger, Brenda A. Schulman
Summary: E3 ligases are typically classified by hallmark domains such as RING and RBR. However, many neddylated CRLs and ARIH family E3 ligases form E3-E3 super-assemblies, which account for nearly half of all ubiquitin ligases in humans. By using activity-based chemical probes and cryo-electron microscopy, it has been shown that the E3-E3 mechanism can ubiquitylate diverse substrates, providing insights into the widespread ubiquitylation mechanism.
Article
Pharmacology & Pharmacy
Senfeng Xiang, Xiaoxian Shi, Pengfei Chen, Yifan Chen, Shaowei Bing, Xizhi Jin, Ji Cao, Jinhu Wang, Bo Yang, Xuejing Shao, Qiaojun He, Meidan Ying
Summary: The research focuses on the substrate adaptors of CRL3, specifically the Kelch-like (KLHL) family proteins. The study identified 24 KLHL proteins with tumor promotion function and 13 KLHL proteins with high clinical significance in cancer therapy. Additionally, the novel biological function of KLHL13 as a vital factor contributing to malignant progression in lung cancer was clarified.
PHARMACOLOGICAL RESEARCH
(2021)
Review
Cell Biology
Carlos Pla-Prats, Nicolas H. Thoma
Summary: The majority of human proteins form multimeric complexes with defined compositions and structures. Recent research has shown that E3 ubiquitin ligases play a crucial role in overseeing the assembly of protein complexes and ensuring their quality control. However, unanswered questions remain regarding their mechanism of action.
TRENDS IN CELL BIOLOGY
(2022)
Article
Physiology
Gustavo R. Ares
Summary: This study found that cGMP mediates the ubiquitination of NKCC2 through the cullin-RING E3 ubiquitin ligase complex, thus regulating surface NKCC2 levels and reducing the reabsorption of sodium chloride. This finding provides new targets for the regulation of NKCC2 expression and activity.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
Article
Microbiology
Kelong Ma, Rundong Shu, Hongtao Liu, Jiaqi Fu, Zhao-Qing Luo, Jiazhang Qiu
Summary: Legionella pneumophila, a pathogenic bacteria, can create an environment conducive to its replication by exploiting host cell signaling pathways and the ubiquitin system. In this study, we identified a novel effector protein, Lug15, which functions as an E3 ligase and remodels the Legionella phagosome.
Article
Biochemistry & Molecular Biology
Lu Gong, Samuel Bates, Yujun Li, Xin Lin, Wenyi Wei, Xiaobo Zhou
Summary: Research found that SNPs within the FAM13A gene are significantly associated with chronic obstructive pulmonary disease and lung function. After treatment with cigarette smoke extract, FAM13A protein is phosphorylated at the serine 312 residue by AKT kinase and recognized by the CULLIN4A/DCAF1 E3 ligase complex, leading to its ubiquitination-mediated degradation. Additionally, AKT activation also leads to downregulation of FAM13A protein levels in mice with influenza or naphthalene-induced lung injury. Functionally, reduced FAM13A protein levels accelerate epithelial cell proliferation in murine lungs during the recovery phase after injury.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Review
Oncology
Yiqing Yang, Shiming Tan, Yaqian Han, Lisheng Huang, Ruiqian Yang, Zifan Hu, Yi Tao, Linda Oyang, Jinguan Lin, Qiu Peng, Xianjie Jiang, Xuemeng Xu, Longzheng Xia, Mingjing Peng, Nayiyuan Wu, Yanyan Tang, Xiaoling Li, Qianjin Liao, Yujuan Zhou
Summary: Tripartite motif-containing 28 (TRIM28) is a member of the tripartite motif (TRIM) family that binds and degrades its downstream target, while also acting as a transcription co-factor to inhibit gene expression. Increasing evidence has shown the crucial role of TRIM28 in tumor genesis and progression. This review highlights the involvement of TRIM28 in tumor proliferation, migration, invasion, cell death, stemness sustainability, and immune regulation. Due to its significance in tumors, TRIM28 may serve as a potential target for anti-tumor therapy, as well as play a pivotal role in tumor diagnosis and treatment in the future.
FRONTIERS IN ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Kanako Bessho-Uehara, Kengo Masuda, Diane R. Wang, Rosalyn B. Angeles-Shim, Keisuke Obara, Keisuke Nagai, Riri Murase, Shin-ichiro Aoki, Tomoyuki Furuta, Kotaro Miura, Jianzhong Wu, Yoshiyuki Yamagata, Hideshi Yasui, Michael B. Kantar, Atsushi Yoshimura, Takumi Kamura, Susan R. McCouch, Motoyuki Ashikari
Summary: Two species of rice have been independently domesticated from different ancestral wild species in Asia and Africa. Comparison of mutations that underlie phenotypic and physiological alterations associated with domestication traits in these species gives insights into the domestication history of rice in both regions. Independent mutations in orthologous genes associated with these traits have been documented in the two cultivated species, but the selection for awnlessness targeted different genes in O. sativa and O. glaberrima.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Masato Mizuno, Shuhei Ebine, Okuto Shounai, Shizuka Nakajima, Shota Tomomatsu, Ken Ikeuchi, Yoshitaka Matsuo, Toshifumi Inada
Summary: This study reveals that polytryptophan sequences can induce Rqc2-independent ribosome-associated quality control (RQC), and this process does not require CAT-tailing. Polytryptophan sequences also induce ribosome-associated quality control coupled with canonical no-go mRNA decay (NGD) and ribosome-associated quality control uncoupled with NGD.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biotechnology & Applied Microbiology
Tae Hwan Shin, Abdurazak Aman Ketebo, Da Yeon Lee, Seungah Lee, Seong Ho Kang, Shaherin Basith, Balachandran Manavalan, Do Hyeon Kwon, Sungsu Park, Gwang Lee
Summary: Overdose of MNPs@SiO2(RITC) induced lipid peroxidation and decreased membrane fluidity in HEK293 cells. The aspect ratio of cells decreased, traction force increased, and cell movement velocity decreased. Metabotranscriptomics network analysis revealed interplay among lipid peroxidation, focal adhesion, and cell movement.
JOURNAL OF NANOBIOTECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Eunkyeong Kim, Jun Kim, Chuna Kim, Junho Lee
Summary: Chromosome fusion and rearrangement triggered by telomere dysfunction can lead to genome instability. Variants generated by telomere dysfunction accumulate along all chromosomes, with diverse types of telomere damage processing observed at the nucleotide level in chromosome end structures.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Chuna Kim, Sanghyun Sung, Jong-Seo Kim, Hyunji Lee, Yoonseok Jung, Sanghee Shin, Eunkyeong Kim, Jenny J. Seo, Jun Kim, Daeun Kim, Hiroyuki Niida, V. Narry Kim, Daechan Park, Junho Lee
Summary: Telomeres are part of a highly refined system for maintaining the stability of linear chromosomes, with most relying on repetitive sequences and telomerase enzymes. However, in some cases, an alternative lengthening of telomeres (ALT) mechanism is used, which mainly utilises recombination-based replication mechanisms. The study on mouse telomeres reveals the use of non-telomeric sequences and a specific subtelomeric element called mTALT for repairing telomeric DNA damage and composing portions of ALT-dependent telomeres in mouse embryonic stem cells.
NATURE COMMUNICATIONS
(2021)
Article
Engineering, Environmental
Jinyeop Lee, Cheolwoo Bong, Wanyoung Lim, Pan Kee Bae, Abdurhaman Teyib Abafogi, Seung Ho Baek, Yong-Beom Shin, Moon Soo Bak, Sungsu Park
Summary: During the COVID-19 pandemic, researchers found that ozone gas produced by a dielectric barrier discharge plasma generator can rapidly disinfect contaminated face masks while maintaining filtration efficiency. The study demonstrates that this method is effective for at least five uses, protecting the cleanliness and safety of the masks.
ENVIRONMENTAL SCIENCE & TECHNOLOGY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Jiho Park, Song Y. Yeu, Sangjin Paik, Hyungmin Kim, Si-Young Choi, Junyeop Lee, Jinho Jang, Semin Lee, Youngil Koh, Hyunsook Lee
Summary: Loss of BubR1 acetylation leads to chromosomal rearrangement and genetic instability in mice, with replication stress playing a key role in these processes. Moreover, defects in BubR1 acetylation in mitosis contribute to tumorigenesis, as observed in human cancer cells with whole-arm translocations demonstrating similar defects.
Article
Chemistry, Inorganic & Nuclear
Anjong Florence Tikum, Wanyoung Lim, Maxine Mambo Fortibui, Sohyun Lee, Sungsu Park, Jinheung Kim
Summary: A new palladium complex probe has been developed for detecting carbon monoxide with fast response and high selectivity and stability. The probe is capable of detecting CO in aqueous buffer as well as in living cells, providing a potential real-time indicator for studying CO-involved reactions in biological systems.
INORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Jaewon Kim, Atsushi Tamura, Sachiko Tsukita, Sungsu Park
Summary: Immature cell monolayers are susceptible to tensile strain, leading to dynamic changes in cell morphology that can be explained by an increase in di-phosphorylated myosin light chain (pp-MLC). The study suggests that a miniaturized stretching device can be used to investigate the morphological response of epithelial cell monolayers to tensile strain.
JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY
(2021)
Article
Nanoscience & Nanotechnology
Abdurazak Aman Ketebo, Chanyong Park, Jaewon Kim, Myeongjun Jun, Sungsu Park
Summary: The study found that Filamin A (FLNa) plays an important role in cell polarization, migration speed, and invasiveness in U87 glioma cells.
Article
Cell Biology
Soungyub Ahn, Heeseung Yang, Sangwon Son, Hyun Sik Lee, Dongjun Park, Hyunsoo Yim, Hee-Jung Choi, Peter Swoboda, Junho Lee
Summary: Cilia are crucial for environmental interaction and tissue function. This study uncovers the regulatory mechanism that confers a specific identity on IL2 neurons in C. elegans, revealing the conservation of genetic modules for distinct behaviors.
Article
Multidisciplinary Sciences
Junyeop Lee, Keewon Sung, So Young Joo, Jun-Hyeon Jeong, Seong Keun Kim, Hyunsook Lee
Summary: The dynamic interaction between BRCA2 and telomeric G-quadruplex (G4) plays a crucial role in telomere replication. Binding of BRCA2 remodels telomeric G4 structure, allowing the restart of stalled replication forks driven by G4 and preventing telomere breakdown.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Bram Cockx, Sven Van Bael, Rose Boelen, Elke Vandewyer, Heeseung Yang, Tuan Anh Le, Johnathan J. Dalzell, Isabel Beets, Christina Ludwig, Junho Lee, Liesbet Temmerman
Summary: Neuropeptides play a crucial role in regulating animal physiology and behavior. This study developed a targeted peptidomics method for C.elegans and identified numerous neuropeptides that are more abundant in its dauer stage compared to L3 juveniles. Through further experiments, flp-7 and flp-11 were identified as novel regulators of nictation behavior.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Biotechnology & Applied Microbiology
Hyunji Lee, Jun Kim, Junho Lee
Summary: Recent advances in long-read sequencing technologies have enabled accurate identification of genetic variants. In this study, two Caenorhabditis elegans strains were used to compare the performance of two long-read sequencing platforms, HiFi and CLR. HiFi identified more true-positive variants and fewer false-positive variants compared to CLR. Additionally, assembly-based variant calling was shown to be effective for detection of large insertions using accurate long-read sequencing data.
Article
Genetics & Heredity
Daisy S. Lim, Jun Kim, Wonjoo Kim, Nari Kim, Sang-Hee Lee, Daehan Lee, Junho Lee
Summary: Under adverse environmental conditions, nematodes enter the dauer stage, which is essential for survival. The daf-42 gene is crucial for the development into the dauer stage in Caenorhabditis elegans, as its mutation results in the inability to form dauers. The daf-42 mutation affects the transcription of genes involved in larval physiology and dauer metabolism.
Article
Genetics & Heredity
Bo Yun Lee, Jun Kim, Junho Lee
Summary: This study traced the evolution of presence-absence variant (PAV) genes in C. elegans strains and identified previously unannotated genes. The researchers also found that some of these potentially new genes have alternative alleles in other wild strains, which exhibit transposon or accumulation of small insertions/deletions signatures.
NAR GENOMICS AND BIOINFORMATICS
(2022)
Article
Genetics & Heredity
Jiseon Lim, Jun Kim, Junho Lee
Summary: The study found natural variation in progeny number and male proportion among wild C. elegans strains, with no correlation between the two traits. Significant genetic associations with male production rate were identified in different reproductive periods.
G3-GENES GENOMES GENETICS
(2021)