Review
Immunology
Ting Zhong, Kang Lei, Xiaoxi Lin, Zhiguo Xie, Shuoming Luo, Zhiguang Zhou, Bin Zhao, Xia Li
Summary: Protein ubiquitination, an important form of posttranslational modification, plays a crucial role in regulating T cell development and differentiation. Recent research has shown that the ubiquitination system is involved in the regulation of thymocyte developmental programs. This review summarizes the molecular mechanisms and cellular pathways associated with thymocyte ubiquitination, providing insights into cell fate determination and potential therapeutic strategies for autoimmune diseases and cancer.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Neurosciences
Molly Hodul, Bethany J. Rennich, Eric S. Luth, Caroline L. Dahlberg, Peter Juo
Summary: This study identifies an activity-dependent mechanism that regulates WDR-20 expression and shows that WDR-20 works together with USP-46 and WDR-48 to promote surface levels of the C. elegans AMPAR GLR-1.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Medicine, Research & Experimental
Ravi Chauhan, Ashna Gupta, Lakshay Malhotra, Ajaz A. Bhat, Raj K. Pandita, Tariq Masoodi, Gunjan Dagar, Hana Q. Sadida, Sara K. Al-Marzooqi, Atul Batra, Sameer Bakhshi, Mehar Chand Sharma, Pranay Tanwar, Shah Alam Khan, Ethayathulla Abdul Samath, Shahab Uddin, Ammira S. Al-Shabeeb Akil, Mohammad Haris, Muzafar A. Macha, Tej K. Pandita, Mayank Singh
Summary: Analysis of the TCGA database showed that increased expression of USP37 was associated with decreased progression-free survival (PFS) in osteosarcoma patients. Further research revealed that USP37 overexpression provided a survival advantage, while its depletion increased sensitivity to replication stress in osteosarcoma cells. Additionally, USP37 was found to physically interact with PCNA through unique residues. This study expands our understanding of how USP37 regulates replication stress and suggests its potential as a therapeutic target in osteosarcoma.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Yu Meng, Huiyan Sun, Yayun Li, Shuang Zhao, Juan Su, Furong Zeng, Guangtong Deng, Xiang Chen
Summary: Ferroptosis is regulated by ubiquitination at post-translational level, in which E3 ubiquitin ligases (E3s) and deubiquitinating enzymes (DUBs) play crucial roles. The dysregulation of ubiquitin system enzymes contributes to the progression of multiple cancers. Understanding the regulatory networks of ferroptosis mediated by E3s or DUBs may provide new opportunities for cancer therapy.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Review
Oncology
Xiao-Xin Sun, Yanping Li, Rosalie C. Sears, Mu-Shui Dai
Summary: Ubiquitination and SUMOylation are crucial mechanisms regulating the stability and activity of MYC protein, playing key roles in cancer and thereby serving as potential therapeutic targets.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Zhenzhu Hou, Wanyan Shi, Jinan Feng, Wei Wang, Enrun Zheng, Hanbin Lin, Cheng Yu, Lisheng Li
Summary: Some deubiquitinating enzymes can regulate their own protein stability in an enzymatic activity- and homomeric interaction-dependent manner, such as USP29 which deubiquitinates itself to protect against degradation, with the N-terminal region critical for its stability. This provides new insights into the diverse regulation of DUBs.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Oncology
Arun Pandian Chandrasekaran, Bharathi Suresh, Neha Sarodaya, Na-Re Ko, Seung-Jun Oh, Kye-Seong Kim, Suresh Ramakrishna
Summary: Among other cancers, colorectal carcinoma (CRC) is a leading cause of death worldwide. The study identified USP29 as highly expressed in CRC and may contribute to its progression. Depletion of USP29 in cancer cells reduced growth and tumor volume, suggesting it as a potential target for therapy.
Review
Biochemistry & Molecular Biology
Sachio Tsuchida, Tomohiro Nakayama
Summary: Oral health is crucial for overall well-being and may indicate systemic diseases, with the ubiquitin system playing a role in cellular functions and DNA repair. Deubiquitinating enzymes are essential regulators of ubiquitination-mediated degradation and have significant impacts on cellular pathways and biological processes. Research highlights the relationship between ubiquitination, deubiquitination, and oral diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Wenying Gao, Yajuan Rui, Guangquan Li, Chenyang Zhai, Jiaming Su, Han Liu, Wenwen Zheng, Baisong Zheng, Wenyan Zhang, Yongjun Yang, Shucheng Hua, Xiaofang Yu
Summary: The study demonstrates that specific deubiquitinating enzymes (DUBs) can inhibit viral proteins from HIVs/SIVs, highlighting a previously unrecognized interplay between DUBs and viral replication. This suggests that enhancing the antiviral activity of DUBs represents a promising strategy against HIVs/SIVs.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Justin Taft, Michael Markson, Diana Legarda, Roosheel Patel, Mark Chan, Louise Malle, Ashley Richardson, Conor Gruber, Marta Martin-Fernandez, Grazia M. S. Mancini, Jan A. M. van Laar, Philomine van Pelt, Sofija Buta, Beatrijs H. A. Wokke, Ira K. D. Sabli, Vanessa Sancho-Shimizu, Pallavi Pimpale Chavan, Oskar Schnappauf, Raju Khubchandani, Muserref Kasap Cuceoglu, Seza Ozen, Daniel L. Kastner, Adrian T. Ting, Ivona Aksentijevich, Iris H. I. M. Hollink, Dusan Bogunovic
Summary: The loss of TBK1 leads to decreased IFN-I induction but affects autoinflammation and TNF-induced cell death, and treatment with anti-TNF can improve the clinical condition of patients.
Review
Chemistry, Medicinal
Lucas Cruz, Paula Soares, Marcelo Correia
Summary: Ubiquitination and deubiquitinating enzymes play crucial roles in cellular regulation, especially in the development of cancer. USPs, as the largest family of DUBs, are involved in various cellular functions and have been studied as novel targets for cancer therapy.
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
Ying Zhang, Imke K. Mandemaker, Syota Matsumoto, Oded Foreman, Christopher P. Holland, Whitney R. Lloyd, Kaoru Sugasawa, Wim Vermeulen, Jurgen A. Marteijn, Paul J. Galardy
Summary: Nucleotide excision repair pathway is essential for fixing DNA damage, and the UV-DDB complex plays a key role in recognizing and repairing UV-induced lesions. The tumor suppressor USP44 deubiquitinates DDB2 to prevent premature degradation, ensuring proper recruitment of repair components. Lack of USP44 leads to impaired repair and increases susceptibility to NER-induced tumors.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
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)
Review
Biochemistry & Molecular Biology
Daisuke Oikawa, Kouhei Shimizu, Fuminori Tokunaga
Summary: Protein ubiquitination is a crucial post-translational modification that regulates numerous cellular functions. OTUD1 is a deubiquitinating enzyme (DUB) with multiple functions, including tumor suppression, regulation of immune responses, and involvement in various diseases. It primarily targets proteins such as p53, SMAD7, and PTEN, and is also involved in antiviral signaling and the reactive oxygen species-mediated oxidative stress response. Overall, OTUD1 is an important therapeutic target for a variety of diseases.
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)
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)
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
Clinical Neurology
Key-Hwan Lim, Sumin Yang, Sung-Hyun Kim, Euiseong Ko, Mingon Kang, Jae-Yeol Joo
Summary: In this study, the authors review the regulation mechanisms of phospholipase C (PLC) in the phosphoinositide signalling pathway and the genetic variations of PLC in brain disorders. They discuss the potential of deep learning to identify PLC mutations in brain disorders. PLC is an essential enzyme in the phosphoinositide signalling pathway, and its mutations are associated with various disorders. The review also highlights the challenges in identifying cryptic PLC mutations and the need for advanced analysis techniques such as deep learning.
Article
Biochemistry & Molecular Biology
Sung-Hyun Kim, Key-Hwan Lim, Sumin Yang, Jae-Yeol Joo
Summary: Neurodegenerative diseases arise from abnormal gene expression and various pathological factors, necessitating a disease-specific integrative genetic approach. This study analyzed the expression of CD48 and CD40 genes in Alzheimer's disease (AD) and found their significant upregulation, particularly in severe AD cases. The overexpression of these genes was associated with tau aggregation and enrichment of the NF-kappa B signaling pathway. These findings suggest that CD48 and CD40 genes may serve as novel AD-related genes and potential targets for diagnosis and treatment.
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.