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1

Lee, Jaeseok, Youngjun Lee, Young Mee Jung, Ju Hyun Park, Hyuk Sang Yoo, and Jongmin Park. "Discovery of E3 Ligase Ligands for Target Protein Degradation." Molecules 27, no. 19 (2022): 6515. http://dx.doi.org/10.3390/molecules27196515.

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Target protein degradation has emerged as a promising strategy for the discovery of novel therapeutics during the last decade. Proteolysis-targeting chimera (PROTAC) harnesses a cellular ubiquitin-dependent proteolysis system for the efficient degradation of a protein of interest. PROTAC consists of a target protein ligand and an E3 ligase ligand so that it enables the target protein degradation owing to the induced proximity with ubiquitin ligases. Although a great number of PROTACs has been developed so far using previously reported ligands of proteins for their degradation, E3 ligase ligand
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2

Tomkinson, Alan E., Tasmin Naila, and Seema Khattri Bhandari. "Altered DNA ligase activity in human disease." Mutagenesis 35, no. 1 (2019): 51–60. http://dx.doi.org/10.1093/mutage/gez026.

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Abstract The joining of interruptions in the phosphodiester backbone of DNA is critical to maintain genome stability. These breaks, which are generated as part of normal DNA transactions, such as DNA replication, V(D)J recombination and meiotic recombination as well as directly by DNA damage or due to DNA damage removal, are ultimately sealed by one of three human DNA ligases. DNA ligases I, III and IV each function in the nucleus whereas DNA ligase III is the sole enzyme in mitochondria. While the identification of specific protein partners and the phenotypes caused either by genetic or chemi
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3

Cao, Weiguo. "DNA ligases and ligase-based technologies." Clinical and Applied Immunology Reviews 2, no. 1 (2001): 33–43. http://dx.doi.org/10.1016/s1529-1049(01)00039-3.

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4

Fang, Deyu, An Chen, and Sang-Myeong Lee. "Inhibition of activation-induced T cell death by AIP2-mediated ubiquitination of EGR2 (35.20)." Journal of Immunology 182, no. 1_Supplement (2009): 35.20. http://dx.doi.org/10.4049/jimmunol.182.supp.35.20.

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Abstract E3 ubiquitin ligases, which target specific molecules for proteolytic destruction, have emerged as key regulators of immune functions. Several E3 ubiquitin ligases, including c-Cbl, Cbl-b, GRAIL, Itch, and Nedd4, have been shown to negatively regulate T-cell activation. Here we report that the HECT-type E3 ligase, AIP2, positively regulates T-cell activation. Ectopic expression of AIP2 in mouse primary T cells enhances their proliferation and IL-2 production by suppressing apoptosis of T cells. AIP2 interacts with and promotes ubiquitin-mediated degradation of EGR2, a zinc finger tran
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5

Kennan, Alan J., V. Haridas, Kay Severin, David H. Lee, and M. Reza Ghadiri. "Ade NovoDesigned Peptide Ligase: A Mechanistic Investigation." Journal of the American Chemical Society 123, no. 9 (2001): 1797–803. http://dx.doi.org/10.1021/ja991266c.

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6

Fanucci, Francesco. "Quaternary shorelines and continental shelf of the Ligurian coast." Zeitschrift für Geomorphologie 31, no. 4 (1987): 463–72. http://dx.doi.org/10.1127/zfg/31/1987/463.

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7

Gu, Jiafeng, Haihui Lu, Brigette Tippin, Noriko Shimazaki, Myron F. Goodman, and Michael R. Lieber. "XRCC4:DNA ligase IV can ligate incompatible DNA ends and can ligate across gaps." EMBO Journal 26, no. 14 (2007): 3506–7. http://dx.doi.org/10.1038/sj.emboj.7601729.

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8

Thayale Purayil, Fayas, Naganeeswaran Sudalaimuthuasari, Ling Li, et al. "Transcriptome Profiling and Functional Validation of RING-Type E3 Ligases in Halophyte Sesuvium verrucosum under Salinity Stress." International Journal of Molecular Sciences 23, no. 5 (2022): 2821. http://dx.doi.org/10.3390/ijms23052821.

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Owing to their sessile nature, plants have developed a tapestry of molecular and physiological mechanisms to overcome diverse environmental challenges, including abiotic stresses. Adaptive radiation in certain lineages, such as Aizoaceae, enable their success in colonizing arid regions and is driven by evolutionary selection. Sesuvium verrucosum (commonly known as Western sea-purslane) is a highly salt-tolerant succulent halophyte belonging to the Aizoaceae family; thus, it provides us with the model-platform for studying plant adaptation to salt stress. Various transcriptional and translation
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9

Gong, Yao, and Yue Chen. "UbE3-APA: a bioinformatic strategy to elucidate ubiquitin E3 ligase activities in quantitative proteomics study." Bioinformatics 38, no. 8 (2022): 2211–18. http://dx.doi.org/10.1093/bioinformatics/btac069.

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Abstract Motivation Ubiquitination is widely involved in protein homeostasis and cell signaling. Ubiquitin E3 ligases are critical regulators of ubiquitination that recognize and recruit specific ubiquitination targets for the final rate-limiting step of ubiquitin transfer reactions. Understanding the ubiquitin E3 ligase activities will provide knowledge in the upstream regulator of the ubiquitination pathway and reveal potential mechanisms in biological processes and disease progression. Recent advances in mass spectrometry-based proteomics have enabled deep profiling of ubiquitylome in a qua
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10

Alomari, Arqam, Robert Gowland, Callum Southwood, et al. "Identification of Novel Inhibitors of Escherichia coli DNA Ligase (LigA)." Molecules 26, no. 9 (2021): 2508. http://dx.doi.org/10.3390/molecules26092508.

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Present in all organisms, DNA ligases catalyse the formation of a phosphodiester bond between a 3′ hydroxyl and a 5′ phosphate, a reaction that is essential for maintaining genome integrity during replication and repair. Eubacterial DNA ligases use NAD+ as a cofactor and possess low sequence and structural homology relative to eukaryotic DNA ligases which use ATP as a cofactor. These key differences enable specific targeting of bacterial DNA ligases as an antibacterial strategy. In this study, four small molecule accessible sites within functionally important regions of Escherichia coli ligase
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11

Sarri, Niki, Natalia Papadopoulos, Johan Lennartsson та Carl-Henrik Heldin. "The E3 Ubiquitin Ligase TRIM21 Regulates Basal Levels of PDGFRβ". International Journal of Molecular Sciences 24, № 9 (2023): 7782. http://dx.doi.org/10.3390/ijms24097782.

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Activation of platelet-derived growth factor (PDGF) receptors α and β (PDGFRα and PDGFRβ) at the cell surface by binding of PDGF isoforms leads to internalization of receptors, which affects the amplitude and kinetics of signaling. Ubiquitination of PDGF receptors in response to ligand stimulation is mediated by the Casitas b-lineage lymphoma (Cbl) family of ubiquitin ligases, promoting internalization and serving as a sorting signal for vesicular trafficking of receptors. We report here that another E3 ligase, i.e., tripartite motif-containing protein 21 (TRIM21), contributes to the ubiquitin
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12

Goto, Jun, Yoichiro Otaki, Tetsu Watanabe, and Masafumi Watanabe. "The Role of HECT-Type E3 Ligase in the Development of Cardiac Disease." International Journal of Molecular Sciences 22, no. 11 (2021): 6065. http://dx.doi.org/10.3390/ijms22116065.

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Despite advances in medicine, cardiac disease remains an increasing health problem associated with a high mortality rate. Maladaptive cardiac remodeling, such as cardiac hypertrophy and fibrosis, is a risk factor for heart failure; therefore, it is critical to identify new therapeutic targets. Failing heart is reported to be associated with hyper-ubiquitylation and impairment of the ubiquitin–proteasome system, indicating an importance of ubiquitylation in the development of cardiac disease. Ubiquitylation is a post-translational modification that plays a pivotal role in protein function and d
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13

Sharma, Chiranjeev, Myeong A. Choi, Yoojin Song, and Young Ho Seo. "Rational Design and Synthesis of HSF1-PROTACs for Anticancer Drug Development." Molecules 27, no. 5 (2022): 1655. http://dx.doi.org/10.3390/molecules27051655.

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PROTACs employ the proteosome-mediated proteolysis via E3 ligase and recruit the natural protein degradation machinery to selectively degrade the cancerous proteins. Herein, we have designed and synthesized heterobifunctional small molecules that consist of different linkers tethering KRIBB11, a HSF1 inhibitor, with pomalidomide, a commonly used E3 ligase ligand for anticancer drug development.
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14

Kounde, Cyrille S., Maria M. Shchepinova, Charlie N. Saunders, et al. "A caged E3 ligase ligand for PROTAC-mediated protein degradation with light." Chemical Communications 56, no. 41 (2020): 5532–35. http://dx.doi.org/10.1039/d0cc00523a.

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15

Wei, Wei, Jian-ye Chen, Ze-xiang Zeng, Jian-fei Kuang, Wang-jin Lu, and Wei Shan. "The Ubiquitin E3 Ligase MaLUL2 Is Involved in High Temperature-Induced Green Ripening in Banana Fruit." International Journal of Molecular Sciences 21, no. 24 (2020): 9386. http://dx.doi.org/10.3390/ijms21249386.

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Harvested banana fruit ripened under warm temperatures above 24 °C remain green peel, leading to severe economic loss. E3 ubiquitin-ligases, as the major components in the ubiquitination pathway, have been implicated to play important roles in temperature-stress responses. However, the molecular mechanism underlying high temperature-triggered stay-green ripening bananas in association with E3 ubiquitin-ligases, remains largely unknown. In this study, a RING-type E3 ubiquitin ligase termed MaLUL2, was isolated and characterized from banana fruit. The MaLUL2 gene contains 1095 nucleotides and en
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16

Toma-Fukai, Sachiko, and Toshiyuki Shimizu. "Structural Diversity of Ubiquitin E3 Ligase." Molecules 26, no. 21 (2021): 6682. http://dx.doi.org/10.3390/molecules26216682.

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The post-translational modification of proteins regulates many biological processes. Their dysfunction relates to diseases. Ubiquitination is one of the post-translational modifications that target lysine residue and regulate many cellular processes. Three enzymes are required for achieving the ubiquitination reaction: ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin ligase (E3). E3s play a pivotal role in selecting substrates. Many structural studies have been conducted to reveal the molecular mechanism of the ubiquitination reaction. Recently, the structure
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17

FOGAR, Sandra R. "LA MULTIDIMENSIONALIDAD DEL ESTUDIO DEL TERRITORIO Y EL DERECHO A LA TERRITORIALIDAD DESDE UNA PERSPECTIVA DE CONSTRUCCIÓN DE TERRITORIALIDAD." ADNea, no. 8 (November 19, 2020): 132. http://dx.doi.org/10.30972/adn.084580.

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Se parte de describir la naturaleza epistemológica del concepto de territorio. Se asume que su condición de objeto de estudio complejo conduce a buscar respuestas en un campo de análisis más amplio en el que confluyen diversas disciplinas. Se aborda el territorio, escenario de múltiples problemáticas. La mirada multidimensional desde la perspectiva crítica del conocimiento y de lo social posibilita pensar la ocupación e intervención territorial, ligada a escenarios de la realidad que anuncian relaciones de dominación y resistencia, y derivado de ello, la Construcción de Territorialidad como co
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18

Andrews, Paul S., Steve Schneider, Evelyn Yang, et al. "Identification of Substrates of SMURF1 Ubiquitin Ligase Activity Utilizing Protein Microarrays." ASSAY and Drug Development Technologies 8, no. 4 (2010): 471–87. http://dx.doi.org/10.1089/adt.2009.0264.

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19

Corbridge, Emily, Alexandra MacGregor, Raed Al-Saharin, et al. "Brassica napus Plants Gain Improved Salt-Stress Tolerance and Increased Storage Oil Biosynthesis by Interfering with CRL3BPM Activities." Plants 12, no. 5 (2023): 1085. http://dx.doi.org/10.3390/plants12051085.

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Generating new strategies to improve plant performance and yield in crop plants becomes increasingly relevant with ongoing and predicted global climate changes. E3 ligases that function as key regulators within the ubiquitin proteasome pathway often are involved in abiotic stress responses, development, and metabolism in plants. The aim of this research was to transiently downregulate an E3 ligase that uses BTB/POZ-MATH proteins as substrate adaptors in a tissue-specific manner. Interfering with the E3 ligase at the seedling stage and in developing seeds results in increased salt-stress tolera
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20

Sun, Aiqin, Yifei Chen, Xianyan Tian, and Qiong Lin. "The Role of HECT E3 Ubiquitin Ligases in Colorectal Cancer." Biomedicines 11, no. 2 (2023): 478. http://dx.doi.org/10.3390/biomedicines11020478.

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Colorectal cancer (CRC) is estimated to rank as the second reason for cancer-related deaths, and the prognosis of CRC patients remains unsatisfactory. Numerous studies on gastrointestinal cell biology have shown that the E3 ligase-mediated ubiquitination exerts key functions in the pathogenesis of CRC. The homologous to E6-associated protein C-terminus (HECT) family E3 ligases are a major group of E3 enzymes, featured with the presence of a catalytic HECT domain, which participate in multiple cellular processes; thus, alterations in HECT E3 ligases in function or expression are closely related
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21

Wang, Peiwen, Lin Zhu, Ziheng Li, et al. "Genome-Wide Identification of the U-Box E3 Ubiquitin Ligase Gene Family in Cabbage (Brassica oleracea var. capitata) and Its Expression Analysis in Response to Cold Stress and Pathogen Infection." Plants 12, no. 7 (2023): 1437. http://dx.doi.org/10.3390/plants12071437.

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Plant U-box E3 ubiquitin ligases (PUBs) play an important role in growth, development, and stress responses in many species. However, the characteristics of U-box E3 ubiquitin ligase genes in cabbage (Brassica oleracea var. capitata) are still unclear. Here, we carry out the genome-wide analysis of U-box E3 ubiquitin ligase genes in cabbage and identify 65 Brassica oleracea var. capitata U-box E3 ubiquitin ligase (BoPUB) genes in the cabbage genome. Phylogenetic analysis indicates that all 65 BoPUB genes are grouped into six subfamilies, whose members are relatively conserved in the protein do
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22

Tseng, Hui-Min, David Shum, Bhavneet Bhinder, et al. "A High-Throughput Scintillation Proximity-Based Assay for Human DNA Ligase IV." ASSAY and Drug Development Technologies 10, no. 3 (2012): 235–49. http://dx.doi.org/10.1089/adt.2011.0404.

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23

McDermott, Jason E., John R. Cort, Ernesto S. Nakayasu, Jonathan N. Pruneda, Christopher Overall, and Joshua N. Adkins. "Prediction of bacterial E3 ubiquitin ligase effectors using reduced amino acid peptide fingerprinting." PeerJ 7 (June 7, 2019): e7055. http://dx.doi.org/10.7717/peerj.7055.

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Background Although pathogenic Gram-negative bacteria lack their own ubiquitination machinery, they have evolved or acquired virulence effectors that can manipulate the host ubiquitination process through structural and/or functional mimicry of host machinery. Many such effectors have been identified in a wide variety of bacterial pathogens that share little sequence similarity amongst themselves or with eukaryotic ubiquitin E3 ligases. Methods To allow identification of novel bacterial E3 ubiquitin ligase effectors from protein sequences we have developed a machine learning approach, the SVM-
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Vriend, Jerry, Thatchawan Thanasupawat, Namita Sinha, and Thomas Klonisch. "Ubiquitin Proteasome Gene Signatures in Ependymoma Molecular Subtypes." International Journal of Molecular Sciences 23, no. 20 (2022): 12330. http://dx.doi.org/10.3390/ijms232012330.

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The ubiquitin proteasome system (UPS) is critically important for cellular homeostasis and affects virtually all key functions in normal and neoplastic cells. Currently, a comprehensive review of the role of the UPS in ependymoma (EPN) brain tumors is lacking but may provide valuable new information on cellular networks specific to different EPN subtypes and reveal future therapeutic targets. We have reviewed publicly available EPN gene transcription datasets encoding components of the UPS pathway. Reactome analysis of these data revealed genes and pathways that were able to distinguish differ
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Choi, Juyoung, Wonkyung Lee, Gynheung An, and Seong-Ryong Kim. "OsCBE1, a Substrate Receptor of Cullin4-Based E3 Ubiquitin Ligase, Functions as a Regulator of Abiotic Stress Response and Productivity in Rice." International Journal of Molecular Sciences 22, no. 5 (2021): 2487. http://dx.doi.org/10.3390/ijms22052487.

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Ubiquitination is an important environmental stress response, and E3 ubiquitin ligases play a major role in the process. T-DNA insertion mutants of rice, Oscbe1-1, and Oscbe1-2, were identified through the screening of cold stress tolerance at seedling stage. Oscbe1 mutants showed a significantly higher cold stress tolerance in the fresh weight, chlorophyll content, and photosynthetic efficiency than wild type. Molecular prediction showed that OsCBE1 (Oryza sativa Cullin4-Based E3 ubiquitin ligase1) encoded a novel substrate receptor of Cullin4-based E3 ubiquitin ligase complex (C4E3). Whereas
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Sukumaran, Bindu, та Pradeep Bist. "Negative regulation of Nod2-mediated NF-κB activation (INM6P.417)". Journal of Immunology 192, № 1_Supplement (2014): 122.14. http://dx.doi.org/10.4049/jimmunol.192.supp.122.14.

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Abstract The cytoplasmic innate immune receptor NOD2 is required for innate immune defense against Gram-positive and Gram-negative intracellular bacterial pathogens. Dysregulation of NOD2 signaling is implicated in several inflammatory disorders (e.g., Crohn’s disease). However, a mechanistic global understanding of the negative regulation of this pathway needs further studies. Through a genome-scale RNA-interference screen, we identified 75 negative regulatory proteins of NOD1/2-mediated NF-κB activation. We characterized the role of several newly identified negative regulators in the regulat
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27

Tan, Xu, and Ning Zheng. "Hormone signaling through protein destruction: a lesson from plants." American Journal of Physiology-Endocrinology and Metabolism 296, no. 2 (2009): E223—E227. http://dx.doi.org/10.1152/ajpendo.90807.2008.

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Ubiquitin-dependent protein degradation has emerged as a major pathway regulating eukaryotic biology. By employing a variety of ubiquitin ligases to target specific cellular proteins, the ubiquitin-proteasome system controls physiological processes in a highly regulated fashion. Recent studies on a plant hormone auxin have unveiled a novel paradigm of signal transduction in which ubiquitin ligases function as hormone receptors. Perceived by the F-box protein subunit of the SCFTIR1 ubiquitin ligase, auxin directly promotes the recruitment of a family of transcriptional repressors for ubiquitina
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28

Yan, Yuqian, Jingwei Shao, Donglin Ding, et al. "3-Aminophthalic acid, a new cereblon ligand for targeted protein degradation by O’PROTAC." Chemical Communications 58, no. 14 (2022): 2383–86. http://dx.doi.org/10.1039/d1cc06525d.

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In this study, we discovered 3-aminophthalic acid as a new ligand of cereblon (CRBN) E3 ubiquitin ligase and developed a phthalic acid-based O’PROTAC for ERG destruction, expanding the pool of ligands for development of PROTACs, especially O’PROTACs.
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Knop, Jan, Tim Lienemann, Haifa El-Kilani, et al. "Structural Features of a Full-Length Ubiquitin Ligase Responsible for the Formation of Patches at the Plasma Membrane." International Journal of Molecular Sciences 22, no. 17 (2021): 9455. http://dx.doi.org/10.3390/ijms22179455.

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Plant U-box armadillo repeat (PUB-ARM) ubiquitin (Ub) ligases have important functions in plant defense through the ubiquitination of target proteins. Defense against pathogens involves vesicle trafficking and the formation of extracellular vesicles. The PUB-ARM protein SENESCENCE ASSOCIATED UBIQUITIN E3 LIGASE1 (SAUL1) can form patches at the plasma membrane related to tethering multi-vesicular bodies (MVBs) to the plasma membrane. We uncovered the structure of a full-length plant ubiquitin ligase and the structural requirements of SAUL1, which are crucial for its function in patch formation.
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30

Xu, Keheng, Nan Wu, Wenbo Yao, Xiaowei Li, Yonggang Zhou, and Haiyan Li. "The Biological Function and Roles in Phytohormone Signaling of the F-Box Protein in Plants." Agronomy 11, no. 11 (2021): 2360. http://dx.doi.org/10.3390/agronomy11112360.

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The ubiquitin–proteasome pathway (UPP) is an important protein degradation pathway that can participate in the regulation of the physiological process of organisms by specifically removing abnormal peptides and degrading cell regulators. UPP mainly involves three enzymes, among which the E3 ubiquitin ligase function is central to UPP. E3 ubiquitin ligases can recruit substrate protein for ubiquitination, and they have various forms. Among them, the Skp1–Cul1–F-box (SCF) complex is the most representative member of the cullin RING ubiquitin ligases type in RING-domain E3 ligases, being mainly c
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Anduro Corona, Iván, and Humberto Astiazaran García. "RNF8: ¿BLANCO TERAPÉUTICO POTENCIAL PARA TRATAR EL CÁNCER DE MAMA?" Biotecnia 20, no. 1 (2018): 47–52. http://dx.doi.org/10.18633/biotecnia.v20i1.529.

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El cáncer de mama hereditario se ha asociado con alteraciones en el gen BRCA1, imposibilitando a la célula tumoral reparar las lesiones de doble cadena del ADN por recombinación homóloga. En la célula normal la RH es necesaria para el mantenimiento de la integridad del ADN. Sin embargo, en las células con BRCA1 disfuncional, el ADN es reparado por el sistema de unión de extremos no homólogos propenso a errores en la0reparación del ADN. Esta condición involucra a 53BP1, cuya función es esencial para el sistema UENH, favoreciendo la inestabilidad genómica y la tumorigénesis mamaria. RNF8 es una
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32

Nolte, Johannes Christoph, Marc Schürmann, Catherine-Louise Schepers, Elvira Vogel, Jan Hendrik Wübbeler, and Alexander Steinbüchel. "Novel Characteristics of Succinate Coenzyme A (Succinate-CoA) Ligases: Conversion of Malate to Malyl-CoA and CoA-Thioester Formation of Succinate AnaloguesIn Vitro." Applied and Environmental Microbiology 80, no. 1 (2013): 166–76. http://dx.doi.org/10.1128/aem.03075-13.

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ABSTRACTThree succinate coenzyme A (succinate-CoA) ligases (SucCD) fromEscherichia coli,Advenella mimigardefordensisDPN7T, andAlcanivorax borkumensisSK2 were characterized regarding their substrate specificity concerning succinate analogues. Previous studies had suggested that SucCD enzymes might be promiscuous toward succinate analogues, such as itaconate and 3-sulfinopropionate (3SP). The latter is an intermediate of the degradation pathway of 3,3′-dithiodipropionate (DTDP), a precursor for the biotechnical production of polythioesters (PTEs) in bacteria. ThesucCDgenes were expressed inE. co
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33

Mallela, Abhishek, Maulik K. Nariya, and Eric J. Deeds. "Crosstalk and ultrasensitivity in protein degradation pathways." PLOS Computational Biology 16, no. 12 (2020): e1008492. http://dx.doi.org/10.1371/journal.pcbi.1008492.

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Protein turnover is vital to cellular homeostasis. Many proteins are degraded efficiently only after they have been post-translationally “tagged” with a polyubiquitin chain. Ubiquitylation is a form of Post-Translational Modification (PTM): addition of a ubiquitin to the chain is catalyzed by E3 ligases, and removal of ubiquitin is catalyzed by a De-UBiquitylating enzyme (DUB). Nearly four decades ago, Goldbeter and Koshland discovered that reversible PTM cycles function like on-off switches when the substrates are at saturating concentrations. Although this finding has had profound implicatio
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Woo, Jennifer L., and Arnold J. Berk. "Adenovirus Ubiquitin-Protein Ligase Stimulates Viral Late mRNA NuclearExport." Journal of Virology 81, no. 2 (2007): 575–87. http://dx.doi.org/10.1128/jvi.01725-06.

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ABSTRACT Theadenovirus type 5 (Ad5) E1B-55K and E4orf6 proteins are required together to stimulate viral late nuclear mRNA export to the cytoplasm and to restrict host cell nuclear mRNA export during the late phase of infection. Previous studies have shown that these two viral proteins interact with the cellular proteins elongins B and C, cullin 5, RBX1, and additional cellular proteins to form an E3 ubiquitin-protein ligase that polyubiquitinates p53 and probably one or more subunits of the MRE11-RAD50-NBS1 (MRN) complex, directing their proteasomal degradation. The MRN complex is required fo
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Heras, Gabriel, Arvind Venkat Namuduri, Leonardo Traini, et al. "Muscle RING-finger protein-1 (MuRF1) functions and cellular localization are regulated by SUMO1 post-translational modification." Journal of Molecular Cell Biology 11, no. 5 (2018): 356–70. http://dx.doi.org/10.1093/jmcb/mjy036.

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Abstract The muscle RING-finger protein-1 (MuRF1) is an E3 ubiquitin ligase expressed in skeletal and cardiac muscle tissues and it plays important roles in muscle remodeling. Upregulation of MuRF1 gene transcription participates in skeletal muscle atrophy, on contrary downregulation of protein expression leads to cardiac hypertrophy. MuRF1 gene point mutations have been found to generate protein aggregate myopathies defined as muscle disorder characterized by protein accumulation in muscle fibers. We have discovered that MuRF1 turned out to be also a target for a new post-translational modifi
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36

Cassaday, Jason, Tarak Shah, Justin Murray, et al. "Miniaturization and Automation of an Ubiquitin Ligase Cascade Enzyme-Linked Immunosorbent Assay in 1,536-Well Format." ASSAY and Drug Development Technologies 5, no. 4 (2007): 493–500. http://dx.doi.org/10.1089/adt.2007.076.

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37

St-Pierre, Patrick, Euan Shaw, Samuel Jacques, et al. "A structural intermediate pre-organizes the add adenine riboswitch for ligand recognition." Nucleic Acids Research 49, no. 10 (2021): 5891–904. http://dx.doi.org/10.1093/nar/gkab307.

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Abstract Riboswitches are RNA sequences that regulate gene expression by undergoing structural changes upon the specific binding of cellular metabolites. Crystal structures of purine-sensing riboswitches have revealed an intricate network of interactions surrounding the ligand in the bound complex. The mechanistic details about how the aptamer folding pathway is involved in the formation of the metabolite binding site have been previously shown to be highly important for the riboswitch regulatory activity. Here, a combination of single-molecule FRET and SHAPE assays have been used to character
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Lama, Rati, Samuel L. Galster, Chao Xu, Luke W. Davison, Sherry R. Chemler, and Xinjiang Wang. "Dual Targeting of MDM4 and FTH1 by MMRi71 for Induced Protein Degradation and p53-Independent Apoptosis in Leukemia Cells." Molecules 27, no. 22 (2022): 7665. http://dx.doi.org/10.3390/molecules27227665.

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MDM2 and MDM4 are cancer drug targets validated in multiple models for p53-based cancer therapies. The RING domains of MDM2 and non-p53-binder MDM2 splice isoforms form RING domain heterodimer polyubiquitin E3 ligases with MDM4, which regulate p53 stability in vivo and promote tumorigenesis independent of p53. Despite the importance of the MDM2 RING domain in p53 regulation and cancer development, small molecule inhibitors targeting the E3 ligase activity of MDM2-MDM4 are poorly explored. Here, we describe the synthesis and characterization of quinolinol derivatives for the identification of a
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39

Goettig, Peter. "Reversed Proteolysis—Proteases as Peptide Ligases." Catalysts 11, no. 1 (2020): 33. http://dx.doi.org/10.3390/catal11010033.

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Historically, ligase activity by proteases was theoretically derived due to their catalyst nature, and it was experimentally observed as early as around 1900. Initially, the digestive proteases, such as pepsin, chymotrypsin, and trypsin were employed to perform in vitro syntheses of small peptides. Protease-catalyzed ligation is more efficient than peptide bond hydrolysis in organic solvents, representing control of the thermodynamic equilibrium. Peptide esters readily form acyl intermediates with serine and cysteine proteases, followed by peptide bond synthesis at the N-terminus of another re
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Kim, Jae Ho, Moon Seok Kim, Dae Yeon Kim, Joseph Noble Amoah, and Yong Weon Seo. "Molecular Characterization of U-box E3 Ubiquitin Ligases (TaPUB2 and TaPUB3) Involved in the Positive Regulation of Drought Stress Response in Arabidopsis." International Journal of Molecular Sciences 22, no. 24 (2021): 13658. http://dx.doi.org/10.3390/ijms222413658.

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Plant U-box E3 ubiquitin ligase (PUB) is involved in various environmental stress conditions. However, the molecular mechanism of U-box proteins in response to abiotic stress in wheat remains unknown. In this study, two U-box E3 ligase genes (TaPUB2 and TaPUB3), which are highly expressed in response to adverse abiotic stresses, were isolated from common wheat, and their cellular functions were characterized under drought stress. Transient expression assay revealed that TaPUB2 was localized in the cytoplasm and Golgi apparatus, whereas TaPUB3 was expressed only in the Golgi apparatus in wheat
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Li, Jun-Mei, Mei-Yan Ye, Chaofeng Wang, et al. "Soybean GmSAUL1, a Bona Fide U-Box E3 Ligase, Negatively Regulates Immunity Likely through Repressing the Activation of GmMPK3." International Journal of Molecular Sciences 24, no. 7 (2023): 6240. http://dx.doi.org/10.3390/ijms24076240.

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E3 ubiquitin ligases play important roles in plant immunity, but their role in soybean has not been investigated previously. Here, we used Bean pod mottle virus (BPMV)-mediated virus-induced gene silencing (VIGS) to investigate the function of GmSAUL1 (Senescence-Associated E3 Ubiquitin Ligase 1) homologs in soybean. When two closely related SAUL1 homologs were silenced simultaneously, the soybean plants displayed autoimmune phenotypes, which were significantly alleviated by high temperature, suggesting that GmSAUL1a/1b might be guarded by an R protein. Interestingly, silencing GmSAUL1a/1b res
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Castillo-Villanueva, Elizabeth, Grisel Ballesteros, Melanie Schmid, et al. "The Mre11 Cellular Protein Is Modified by Conjugation of Both SUMO-1 and SUMO-2/3 during Adenovirus Infection." ISRN Virology 2014 (April 7, 2014): 1–14. http://dx.doi.org/10.1155/2014/989160.

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The adenovirus type 5 (Ad5) E1B 55 kDa and E4 Orf6 proteins assemble a Cullin 5-E3 ubiquitin (Ub) ligase that targets, among other cellular proteins, p53 and the Mre11-Rad50-Nbs1 (MRN) complex for degradation. The latter is also inhibited by the E4 Orf3 protein, which promotes the recruitment of Mre11 into specific nuclear sites to promote viral DNA replication. The activities associated with the E1B 55 kDa and E4 Orf6 viral proteins depend mostly on the assembly of this E3-Ub ligase. However, E1B 55 kDa can also function as an E3-SUMO ligase, suggesting not only that regulation of cellular pr
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Tracz, Michał, Ireneusz Górniak, Andrzej Szczepaniak, and Wojciech Białek. "E3 Ubiquitin Ligase SPL2 Is a Lanthanide-Binding Protein." International Journal of Molecular Sciences 22, no. 11 (2021): 5712. http://dx.doi.org/10.3390/ijms22115712.

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The SPL2 protein is an E3 ubiquitin ligase of unknown function. It is one of only three types of E3 ligases found in the outer membrane of plant chloroplasts. In this study, we show that the cytosolic fragment of SPL2 binds lanthanide ions, as evidenced by fluorescence measurements and circular dichroism spectroscopy. We also report that SPL2 undergoes conformational changes upon binding of both Ca2+ and La3+, as evidenced by its partial unfolding. However, these structural rearrangements do not interfere with SPL2 enzymatic activity, as the protein retains its ability to auto-ubiquitinate in
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Baek, Suk-Hwan, Bin Huang, and Hyeun Wook Chang. "RNF144b is a negative regulator in TLR2-mediated NF-kB activation." Journal of Immunology 196, no. 1_Supplement (2016): 132.4. http://dx.doi.org/10.4049/jimmunol.196.supp.132.4.

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Abstract NF-κB regulates the expression of a various genes involved in diverse cellular processes including inflammation and immunity. Activation of NF-κB requires ubiquitination, a highly conserved and versatile modification that can regulate cell signaling through both proteasome dependent and independent mechanisms. Ubiquitination process is a representative of post-translational modification involved in NF-κB activation of TNFR and TLR signaling. We demonstrated that RNF144b, an E3 ubiquitin ligase, is important factor for the NF-κB regulation in macrophages upon stimulation with TNFa or T
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45

Kats, Ilia, Christian Reinbold, Marc Kschonsak, et al. "Up-regulation of ubiquitin–proteasome activity upon loss of NatA-dependent N-terminal acetylation." Life Science Alliance 5, no. 2 (2021): e202000730. http://dx.doi.org/10.26508/lsa.202000730.

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N-terminal acetylation is a prominent protein modification, and inactivation of N-terminal acetyltransferases (NATs) cause protein homeostasis stress. Using multiplexed protein stability profiling with linear ubiquitin fusions as reporters for the activity of the ubiquitin proteasome system, we observed increased ubiquitin proteasome system activity in NatA, but not NatB or NatC mutants. We find several mechanisms contributing to this behavior. First, NatA-mediated acetylation of the N-terminal ubiquitin–independent degron regulates the abundance of Rpn4, the master regulator of the expression
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Yi, So Young, Myungjin Lee, Suk-Yoon Kwon, Woo Taek Kim, Yong Pyo Lim, and Si-Yong Kang. "RING-Type E3 Ubiquitin Ligases AtRDUF1 and AtRDUF2 Positively Regulate the Expression of PR1 Gene and Pattern-Triggered Immunity." International Journal of Molecular Sciences 23, no. 23 (2022): 14525. http://dx.doi.org/10.3390/ijms232314525.

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The importance of E3 ubiquitin ligases from different families for plant immune signaling has been confirmed. Plant RING-type E3 ubiquitin ligases are members of the E3 ligase superfamily and have been shown to play positive or negative roles during the regulation of various steps of plant immunity. Here, we present Arabidopsis RING-type E3 ubiquitin ligases AtRDUF1 and AtRDUF2 which act as positive regulators of flg22- and SA-mediated defense signaling. Expression of AtRDUF1 and AtRDUF2 is induced by pathogen-associated molecular patterns (PAMPs) and pathogens. The atrduf1 and atrduf2 mutants
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Sheppard, Hilary M., Janet C. Harries, Sagair Hussain, Charlotte Bevan, and David M. Heery. "Analysis of the Steroid Receptor Coactivator 1 (SRC1)-CREB Binding Protein Interaction Interface and Its Importance for the Function of SRC1." Molecular and Cellular Biology 21, no. 1 (2001): 39–50. http://dx.doi.org/10.1128/mcb.21.1.39-50.2001.

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ABSTRACT The transcriptional activity of nuclear receptors is mediated by coactivator proteins, including steroid receptor coactivator 1 (SRC1) and its homologues and the general coactivators CREB binding protein (CBP) and p300. SRC1 contains an activation domain (AD1) which functions via recruitment of CBP and and p300. In this study, we have used yeast two-hybrid and in vitro interaction-peptide inhibition experiments to map the AD1 domain of SRC1 to a 35-residue sequence potentially containing two α-helices. We also define a 72-amino-acid sequence in CBP necessary for SRC1 binding, designat
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Nakotte, Tom, Hongmei Luo, and Jeff Pietryga. "Carrier Density Modulation in PbSe Quantum Dot Films via In-Solution Ligand Exchange." MRS Advances 5, no. 40-41 (2020): 2091–99. http://dx.doi.org/10.1557/adv.2020.254.

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AbstractIn-solution ligand exchange of PbSe QDs is used to examine the effect of capping ligand on the carrier density of PbSe QD films. Results show that carrier density can be modulated by a factor of 5 by choice of ligand without any additional post deposition treatments. Proper fabrication and measurement conditions for calculating carrier densities from C-V measurements using a sandwich structure on P-doped Si/SiO2/Al2O3/QD/Au structure capacitance devices are outlined. Combining carrier density results with field-effect-transistor measurements, promising ligands which display lower carri
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Kołaczkowski, M., P. Mierzejewski, P. Bieńkowski, A. Wesołowska, and A. Newman-Tancredi. "ADN-1184 a monoaminergic ligand with 5-HT6/7receptor antagonist activity: pharmacological profile and potential therapeutic utility." British Journal of Pharmacology 171, no. 4 (2014): 973–84. http://dx.doi.org/10.1111/bph.12509.

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El-Saafin, Farrah, Didier Devys, Steven A. Johnsen, Stéphane D. Vincent, and László Tora. "SAGA-Dependent Histone H2Bub1 Deubiquitination Is Essential for Cellular Ubiquitin Balance during Embryonic Development." International Journal of Molecular Sciences 23, no. 13 (2022): 7459. http://dx.doi.org/10.3390/ijms23137459.

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Ubiquitin (ub) is a small, highly conserved protein widely expressed in eukaryotic cells. Ubiquitination is a post-translational modification catalyzed by enzymes that activate, conjugate, and ligate ub to proteins. Substrates can be modified either by addition of a single ubiquitin molecule (monoubiquitination), or by conjugation of several ubs (polyubiquitination). Monoubiquitination acts as a signaling mark to control diverse biological processes. The cellular and spatial distribution of ub is determined by the opposing activities of ub ligase enzymes, and deubiquitinases (DUBs), which remo
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