Article
Cell & Tissue Engineering
Xi-Biao He, Fang Guo, Kexuan Li, Jiaqing Yan, Sang-Hun Lee
Summary: This study reveals the crucial role of MeCP2 in the specification of midbrain dopamine phenotype in mice, and demonstrates that the timing of MeCP2 expression affects the determination of dopamine phenotype in neural precursor cells (NPCs). Through analysis of DNA methylation dynamics, the study uncovers that Th gene expression is regulated by TET1-mediated demethylation. These findings highlight the significance of MeCP2 expression timing as a novel determining factor for guiding NPCs into the dopamine lineage.
Article
Developmental Biology
Marcella Birtele, Petter Storm, Yogita Sharma, Janko Kajtez, Jenny Nelander Wahlestedt, Edoardo Sozzi, Fredrik Nilsson, Simon Stott, Xiaoling L. He, Bengt Mattsson, Daniella Rylander Ottosson, Roger A. Barker, Alessandro Fiorenzano, Malin Parmar
Summary: This study used single-cell RNA sequencing to analyze the transcriptional profile of human fetal VM during the generation and differentiation of dopamine neurons, revealing that 3D culture conditions are superior to monolayer conditions. These findings can guide stem cell-based therapies and disease modeling in Parkinson's disease.
Article
Neurosciences
Jing Jiang, Xiujuan Hu, Lihua Liu, Zhicheng He, Qingjie Wu, Qunchao Li, Xianwei Hu, Nan Jiang, Chao Liu
Summary: The expression of K48 and K63 ubiquitin lysine linkages in midbrain dopamine neurons is age-related and may be involved in the loss of dopamine neurons. Aging promotes the formation of protein aggregates positive for both K48 and K63 ubiquitin linkages in the substantia nigra pars compacta.
Article
Multidisciplinary Sciences
Xiao Yang, Meihui Song, Ying Wang, Taicong Tan, Zhongyu Tian, Binyuan Zhai, Xuan Yang, Yingjin Tan, Yanding Cao, Shaojun Dai, Shunxin Wang, Liangran Zhang
Summary: This study identifies a molecular pathway for axis length regulation in meiotic cells. It shows that the cohesin regulator Pds5 interacts with proteasomes to regulate the ubiquitination level of chromosome proteins, which affects chromosome axis length. Two ubiquitin E3 ligases, SCF and Ufd4, are involved in this pathway. These findings contribute to our understanding of how Pds5 regulates meiotic chromosome organization and suggest a conserved regulatory mechanism in higher eukaryotes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Plant Sciences
Dania P. Lobaina, Roberto Tarazi, Tamara Castorino, Maite F. S. Vaslin
Summary: The ubiquitin-proteasome system (UPS) is crucial for maintaining cellular balance and plays a key role in DNA repair, gene transcription, and protein activation. Viruses often manipulate the UPS to maintain viral protein levels and evade host defenses. Understanding the mechanisms used by plant viruses to subvert host defenses is important for developing biotechnological approaches for viral resistance.
Article
Neurosciences
Qiu-Yu Yang, Xian-Wei Li, Rong Yang, Ting-Yang Qin, Hong Long, Shi-Bin Zhang, Feng Zhang
Summary: This study suggests that LPS-induced peripheral inflammation may lead to T cell infiltration in the brain to regulate microglia-mediated neuroinflammation, thereby protecting DA neurons.
CNS NEUROSCIENCE & THERAPEUTICS
(2022)
Article
Cell Biology
Nikol Dibus, Eliska Zobalova, Mario A. M. Monleon, Vladimir Korinek, Dominik Filipp, Jana Petrusova, Radislav Sedlacek, Petr Kasparek, Lukas Cermak
Summary: The ubiquitin ligase SCFFBXO38 regulates centromeric chromatin by promoting the degradation of the ZXDB protein. Loss of FBXO38 leads to growth retardation, pathological changes in the testes, decreased sperm production, and reduced fertility in mice. FBXO38 is specifically expressed in Sertoli cells in the testes, and its absence results in Sertoli cell maturation defect and impaired spermatogonial differentiation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Yanan Li, Shujing Li, Huijian Wu
Summary: Cells adapt to environmental stimuli by making changes to combat injury and increase stress tolerance. If the damage is too severe to repair, cells undergo apoptosis to protect the overall population. Protein aggregation can cause serious damage to the cells, but ubiquitin plays a crucial role in clearing these abnormal proteins. Dysregulation of ubiquitin-proteasome system and autophagy can lead to the development of diseases.
Review
Oncology
Yonggang Pei, Erle S. Robertson
Summary: This review discusses the interaction between Epstein-Barr virus (EBV) and the ubiquitin-proteasome system, as well as their importance in EBV-mediated oncogenesis. Deregulation of the ubiquitin-proteasome system plays a critical role in many human cancers, and EBV manipulates this system to induce tumor formation. Recent studies further enhance our understanding of the ubiquitin-proteasome system in EBV infection and provide new strategies for the treatment of EBV-associated cancers.
Review
Biochemistry & Molecular Biology
Gonca cetin, Sandro Klafack, Maja Studencka-Turski, Elke Kruger, Frederic Ebstein
Summary: The ubiquitin-proteasome system (UPS) is a crucial protein degradation system in cells, particularly impacting immune cells and their rapid functional remodeling during immune activation. Recent research has shed light on the molecular mechanisms by which UPS contributes to immune responses and its role in immune disorders like cancer and auto-inflammatory diseases.
Article
Virology
Martin Voss, Vera Braun, Clara Bredow, Peter-Michael Kloetzel, Antje Beling
Summary: Infection with coxsackievirus B3 results in impaired protein homeostasis and accumulation of ubiquitinylated proteins, attributed to viral proteins 2B and 3A. During the exponential replication phase, oxidative damage of membrane proteins is reduced due to the recruitment of glutathione. The proteasome is shown to play a role in processing viral precursor proteins during infection.
Article
Clinical Neurology
Carolina Bianchi, Beatriz Alvarez-Castelao, Alvaro Sebastian-Serrano, Caterina Di Lauro, Lucia Soria-Tobar, Annette Nicke, Tobias Engel, Miguel Diaz-Hernandez
Summary: Recent evidence suggests a causal relationship between neurofibrillary tangles (NFTs) formation and UPS dysfunction in tauopathies, including Alzheimer's disease (AD). This study investigates the impact of ATP, a danger-associated molecule pattern (DAMP) associated with neuroinflammation, on AD-associated UPS dysfunction.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Multidisciplinary Sciences
Afu Fu, Victoria Cohen-Kaplan, Noa Avni, Ido Livneh, Aaron Ciechanover
Summary: The degradation of proteins through the ubiquitin-proteasome system is a complex multistep process that relies on the coordinated activity of various enzymes. Nuclear condensates containing essential components like p62 play a crucial role in protein quality control and degradation, especially under stress conditions. These assemblies, generated through liquid-liquid phase separation, efficiently facilitate proteolysis of nuclear proteins and unassembled proteasome subunits, indicating their involvement in cellular protein quality control.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Robert F. Shearer, Dimitris Typas, Fabian Coscia, Sofie Schovsbo, Thomas Kruse, Andreas Mund, Niels Mailand
Summary: Ubiquitin conjugation to substrate proteins regulates cellular processes and the K27 linkage type is essential for human cell proliferation. K27-linked ubiquitylation predominantly occurs in the nucleus and its disruption impairs nuclear ubiquitylation dynamics and cell cycle progression. K27-linked ubiquitylation supports cell fitness by facilitating p97-dependent processing of ubiquitylated nuclear proteins.
Review
Cell Biology
Jason Q. Tang, Mary M. Marchand, Gianluca Veggiani
Summary: Protein turnover, regulated by the ubiquitin-proteasome system (UPS), is important for cellular homeostasis. Dysregulation of the UPS is associated with diseases and UPS enzymes are attractive therapeutic targets. However, redundancies of UPS enzymes make it challenging to identify precise drug targets. Engineered ubiquitin has emerged as a promising alternative to guide the development of small molecules targeting novel surfaces.
Article
Biochemistry & Molecular Biology
Myung-Sun Kim, Kyunggon Kim, Su Kyung Oh, Gidae Lee, Jin-Ock Kim, Lan Li, Jung-Hyun Park, Kwang-Hyun Baek
Summary: The study successfully prevented ubiquitination of growth hormone hGH by substituting lysine residues with arginine residues, particularly identifying K141R as the most effective substituent to create a long-lasting hGH named AUT-hGH.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Hae-Seul Choi, Kwang-Hyun Baek
Summary: Apoptosis is a structured cell death process involving cell morphology and biochemical changes, and the ubiquitin-proteasome system regulates the protein levels. Targeting UPS enzymes and controlling proteasomal degradation of apoptotic proteins could be a unique approach for cancer treatment.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Sang-Soo Park, Kwang-Hyun Baek
Summary: "Translation: Proteins associated with protein ubiquitination and modifications by Ubls in acute myeloid leukemia" This review discusses the roles of protein ubiquitination and modifications by Ubls in acute myeloid leukemia (AML). It highlights the association between AML-related mutated proteins and Ub and Ubls, as well as the potential of Ubls as therapeutic targets in AML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, General & Internal
Hyoeun Kim, Ji Hye Koh, Jihee Lee, Yeongeun Sim, Sang-Hun Lee, Soo-Jeong Lee, Jun-Woo Ahn, Hyun-Jin Roh, Jeong Sook Kim
Summary: This case report presents a successful treatment for heterotopic cesarean scar pregnancy, using selective potassium chloride injection into the scar pregnancy and uterine cerclage to control vaginal bleeding, resulting in the preservation of the intrauterine pregnancy and full-term delivery.
Article
Biochemistry & Molecular Biology
Su Yeon Kim, Ji-young Lee, Yun-jung Cho, Kwan Hoon Jo, Eun Sook Kim, Je Ho Han, Kwang-Hyun Baek, Sung-dae Moon
Summary: This study found that USP37 is a specific deubiquitinating enzyme for CDC73, and the two proteins interact through specific domains, suggesting that USP37 plays an important role in the stability of CDC73 in HPT-JT syndrome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Hong-Beom Park, Sohyun Hwang, Kwang-Hyun Baek
Summary: This study analyzed the potential substrate proteins of USP7 using bioinformatics tools and confirmed Raf-1 as one of its substrates. By removing ubiquitin from Raf-1, USP7 inhibits the activation of the ERK1/2 signaling pathway, resulting in the suppression of lung adenocarcinoma cell proliferation.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Hae-Seul Choi, Eun-Su Lim, Kwang-Hyun Baek
Summary: The study identified the deubiquitinating enzyme USP12 as being associated with Bax and showed that USP12 regulates Bax by detaching ubiquitin on K63-linked chains. The site-directed mutagenesis of putative ubiquitination sites on Bax confirmed the half-life of the protein.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, General & Internal
Sang Hun Lee, Songsoo Yang, Inkyu Park, Yeong Cheol Im, Gyu Yeol Kim
Summary: This case report describes a 33-year-old pregnant woman who experienced a sudden onset of epigastric pain at 18 weeks of pregnancy due to a ruptured SAA. After emergent intervention and surgery, the woman recovered without complications and was discharged 15 days postoperatively, even though the fetus was found to be dead during resuscitation.
WORLD JOURNAL OF CLINICAL CASES
(2022)
Article
Biochemistry & Molecular Biology
Sang -Soo Park, Hyeon-Ah Do, Hong-Beom Park, Hae-Seul Choi, Kwang-Hyun Baek
Summary: a-synuclein, a protein involved in neurodegenerative diseases like Parkinson's disease and Lewy body dementia, is regulated by the ubiquitin-proteasome system (UPS). In this study, researchers found that the deubiquitinating enzyme YOD1 interacts with a-synuclein and removes multiple types of ubiquitin chains from it. YOD1 also destabilizes a-synuclein by upregulating the E3 ligase NEDD4. These findings suggest that YOD1 may be a new regulator in the NEDD4-a-synuclein pathway.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Dong Gi Lee, Young-Kwang Kim, Kwang-Hyun Baek
Summary: The development of functional neural circuits in the CNS requires the production of various types of neurons and glial cells at the right time and place. Neurodegenerative diseases can occur when there is severe neuronal loss. Cell therapy using stem cells and gene therapy through cell fate conversion are potential treatments for these diseases. This report reviews the role of bHLH in neuronal differentiation, reprogramming, and cell fate determination, and investigates its importance in directing neural and glial cell fate specification and differentiation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Hong-Beom Park, Yosuk Min, Sohyun Hwang, Kwang-Hyun Baek
Summary: Ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme that removes mono and polyubiquitin chains from target proteins. It has opposing roles as an oncogene or tumor suppressor in different cancer types. USP7 is involved in various cellular processes such as cell cycle, apoptosis, DNA repair, chromatin remodeling, and epigenetic regulation, through deubiquitination of substrates including p53, MDM2, Myc, and PTEN. In this study, a novel substrate of USP7 was identified and its potential role in cancer related to ETS2 dysregulation was proposed.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Medicine, Research & Experimental
Hong-Beom Park, Bum-Chae Choi, Kwang-Hyun Baek
Summary: In this study, potential substrates of ITI-H4 were identified through immunoprecipitation and MALDI-TOF/MS analysis. Among them, PGK1 was found to be a binding protein of ITI-H4. PGK1 increases ITI-H4 expression and blocks its cleavage mediated by KLKB1. It also inhibits pro-inflammatory response by inhibiting the JAK2/STAT3 signaling pathway. Therefore, PGK1 is expected to have cellular functions in the pathogenesis of ITI-H4-related inflammatory diseases.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Multidisciplinary Sciences
Soo-Ji Kang, Chang-Zhu Pei, Da-Hye Lee, Jong-Eun Ha, Kwang-Hyun Baek
Summary: Art therapy has a positive effect on emotional and physical changes in patients with alcohol use disorder, including alleviating depression, anxiety, impulsivity, and alcohol dependence. This study strengthens the connection between biomedical science and mental health in the treatment of alcohol use disorder.
Review
Genetics & Heredity
Yosuk Min, Hong-Beom Park, Kwang-Hyun Baek, Sohyun Hwang
Summary: In ovarian cancer, the survival rate is much higher for early stages than for advanced stages. However, most patients are diagnosed in the advanced stages and often experience recurrence. To address this, new biomarkers for early diagnosis and treatment are needed. This review focuses on deubiquitinating enzymes and their regulated substrates in ovarian cancer cells, which could aid in the discovery of biomarkers and therapeutic candidates.
Article
Cell Biology
Chang-Zhu Pei, Bum-Chae Choi, Jun-Hyeok Park, Hyo Young Park, Jinyoung Paek, Kyung-Ju Lee, Bo-Seong Yun, Young Ju Kim, Kwang-Hyun Baek
Summary: The expression of High-temperature requirement factor A4 (HtrA4) mRNA is lower in patients with recurrent pregnancy loss (RPL) compared to the control group. Knockout BeWo cells with reduced invasion and fusion capacity and increased proliferation and migration were created using the CRISPR/Cas9 system. Depletion of HtrA4 in JEG3 cells resulted in decreased invasion capacity but increased migration capacity. The findings suggest that HtrA4 may be associated with placental dysfunction in RPL patients.
