Article
Biochemistry & Molecular Biology
Daniel Salas-Lloret, Roman Gonzalez-Prieto
Summary: Ubiquitination and SUMOylation are dynamic post-translational modifications that regulate cellular processes. The understanding of these modifications has been increased by the development of mass spectrometry-based approaches. This translated article provides a concise overview of the basic mechanisms of ubiquitination and SUMOylation, as well as recent MS-based approaches for specific target identification.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Hongbiao Ran, Chunyan Li, Ming Zhang, Jincheng Zhong, Hui Wang
Summary: Ubiquitination, a post-transcriptional modification, plays a crucial role in protein degradation and is involved in various physiological and pathological processes, including animal adipogenesis. The E3 ligases have been found to regulate adipogenesis, but their role in the recognition and connection between substrate and ubiquitin during ubiquitination has been overlooked. This review summarizes the regulatory and modification targets of E3 ligases in animal adipogenesis, explains the regulatory mechanisms in lipogenic pathways, and analyzes existing positive results, providing valuable research directions for further understanding the regulatory mechanisms of E3 ligases in animal adipogenesis.
Article
Biochemistry & Molecular Biology
Adi Ulman, Tal Levin, Bareket Dassa, Aaron Javitt, Assaf Kacen, Merav D. Shmueli, Avital Eisenberg-Lerner, Daoud Sheban, Simon Fishllevich, Emmanuel D. Levy, Yifat Merbl
Summary: Protein modification by ubiquitin or SUMO can alter protein function, stability and activity. This study identified sites in the human proteome where proteins were modified by both ubiquitin and SUMO, termed SAMs. SAM-containing proteins are associated with various biological functions, and comparison with non-overlapping modification sites revealed altered properties such as cellular localization or abundance of host proteins. Mutating the SAM motif in a protein can influence its ubiquitination, localization, and abundance, as demonstrated in S. cerevisiae.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Samuel Smalley, Hanjo Hellmann
Summary: This review provides an overview of how ubiquitin and similar proteins modify target proteins in plants to rapidly change their stability and activity, with a focus on their contribution to stress tolerance. The study also explores the potential use of these pathways for generating more robust crop plants to cope with stress situations.
Article
Biochemistry & Molecular Biology
Shanshan Xu, Maria E. Gierisch, Anna Katharina Schellhaus, Ina Poser, Simon Alberti, Florian A. Salomons, Nico P. Dantuma
Summary: The absence of stress granules in cells has a negative impact on the functionality of the nuclear ubiquitin-proteasome system (UPS). Defective ribosome products (DRiPs) in stress granule-deficient cells accumulated at nucleoli instead of stress granules, accompanied by redistribution and enhanced degradation of SUMOylated proteins. Depletion of the SUMO-targeted ubiquitin ligase RNF4 restored the functionality of the nuclear UPS in stress granule-deficient cells. Stress granule-deficient cells showed increased formation of mutant ataxin-1 nuclear inclusions under thermal stress. These findings highlight the importance of stress granules in sequestering cytosolic misfolded proteins and preventing their accumulation in the nucleus.
Article
Multidisciplinary Sciences
Lingmin Yuan, Zongyang Lv, Melanie J. Adams, Shaun K. Olsen
Summary: By determining the structure of a covalently trapped E1-E2-ubiquitin thioester mimetic, researchers identified two distinct conformations of the E1-E2-Ub complex which suggest the presence of an affinity switch mechanism facilitating thioester transfer.
NATURE COMMUNICATIONS
(2021)
Article
Virology
Wing-Hang Ip, Michael H. Tatham, Steewen Krohne, Julia Gruhne, Michael Melling, Tina Meyer, Britta Gornott, Luca D. Bertzbach, Ronald T. Hay, Estefania Rodriguez, Thomas Dobner
Summary: This study used quantitative SUMO proteomics to analyze the cellular consequences of E1B-55K-mediated host cell modulation and adenovirus infection. The results showed that changes in the SUMOylated proteome could regulate DNA damage response, cell cycle control, chromatin assembly, and gene transcription. Additionally, a SUMO-dependent, ubiquitin-mediated degradation mechanism for some SUMO substrates was identified, suggesting that E1B-55K might use multiple mechanisms to alter restrictive cellular pathways.
JOURNAL OF VIROLOGY
(2023)
Article
Virology
Behdokht Jan Fada, Udayan Guha, Yi Zheng, Eleazar Reward, Elie Kaadi, Ayette Dourra, Haidong Gu
Summary: It was found that ICP0 E3 enzyme continuously degrades PML I through a specific mechanism to prevent the reformation of ND10 complex.
Article
Biochemistry & Molecular Biology
Jiawei Xiong, Fabin Yang, Fan Wei, Feng Yang, Honghui Lin, Dawei Zhang
Summary: HLS1 plays a key role in the development of the apical hook in plants, and SIZ1 regulates the rapid opening of the apical hook by mediating HLS1 SUMOylation. The opening of the apical hook is associated with a decrease in SIZ1 transcript levels, leading to reduced HLS1 SUMOylation. In addition, HY5 promotes the rapid opening of the apical hook by inhibiting SIZ1 transcription.
Article
Biochemistry & Molecular Biology
Bin Lv, Yida Pan, Daisen Hou, Ping Chen, Jun Zhang, Yiwei Chu, Mingqi Li, Yan Zeng, Dongqin Yang, Jie Liu
Summary: This study found that ring finger protein 4 (RNF4) is essential for the growth of hepatocellular carcinoma (HCC). Silencing RNF4 suppressed HCC cell growth, induced apoptosis, increased DNA damage, and enhanced sensitivity to DNA damage drugs and radiation. These findings suggest that RNF4 may serve as a novel target for suppressing HCC growth and improving the efficacy of DNA damage therapeutic agents.
Review
Chemistry, Multidisciplinary
Kristin M. Riching, Elizabeth A. Caine, Marjeta Urh, Danette L. Daniels
Summary: Targeted protein degradation is a crucial therapeutic approach that requires optimization of multiple parameters to achieve rapid degradation, high potency, and sustained target loss. Degradation is only the first milestone in degrader development, and understanding the dynamic cellular degradation profiles is essential for discovering effective therapeutic agents more efficiently.
CHEMICAL SOCIETY REVIEWS
(2022)
Article
Immunology
Shuyan Lai, Mengqiong Xu, Yaohao Wang, Ruilin Li, Chuan Xia, Sisi Xia, Jun Chen
Summary: SUMO post-translational modification plays a crucial role in the replication process of human cytomegalovirus (HCMV) by promoting UL44 protein interaction with host cell antiviral devices and inhibiting viral replication. This novel mechanism highlights the importance of SUMOylation in regulating viral subnuclear localization and controlling herpesvirus replication.
Article
Chemistry, Medicinal
Ziqin Yan, Xilin Lyu, Dongze Lin, Gaoxing Wu, Yang Gong, Xuelian Ren, Jian Xiao, Jianfeng Lou, He Huang, Yi Chen, Yujun Zhao
Summary: Targeted degradation of BET family proteins BRD2/3/4 or only BRD4 with PROTAC molecules has shown promising potential in cancer treatment. This study introduces a novel PROTAC molecule 24 that selectively degrades cellular BRD3 and BRD4-L, but not BRD2 or BRD4-S, in multiple cancer cell lines. The selectivity is attributed to differences in protein degradation kinetics and cell line types. The optimized lead compound 28 exhibits selective degradation of BRD3 and BRD4-L in vivo and demonstrates significant antitumor activity in a MM.1S mouse xenograft model. This research highlights the importance of selective protein degradation in cancer research and therapeutics.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Gurusamy Hariharasudhan, Seo-Yeon Jeong, Min-Ji Kim, Sung Mi Jung, Gwanwoo Seo, Ju-Ran Moon, Sumi Lee, In-Youb Chang, Younghoon Kee, Ho Jin You, Jung-Hee Lee
Summary: SUMOylation of RAD51 is crucial for its recruitment to chromatin and HR repair. TOPORS-mediated RAD51 SUMOylation plays a key role in promoting HR repair and genomic maintenance.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Medicinal
He Chen, Jing Liu, H. Umit Kaniskan, Wenyi Wei, Jian Jin
Summary: This study presents a general strategy for delivering IMiD-based molecular glues and PROTACs to FOLR1-expressing cancer cells, effectively degrading fusion proteins in cancer cells with the potential to ameliorate toxicity.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Virology
Alexis S. Chasseur, Gabrielle Trozzi, Celine Istasse, Astrid Petit, Perrine Rasschaert, Caroline Denesvre, Benedikt B. Kaufer, Luca D. Bertzbach, Benoit Muylkens, Damien Coupeau
Summary: Circular RNAs (circRNAs) have recently been rediscovered and found to be involved in gene regulation and cancer development. This study focused on viral circRNAs in Marek's disease virus (MDV) infections and identified a variety of viral circRNAs expressed during viral replication, latency, and reactivation. The circRNA expression mainly occurred in transcriptional units of major viral oncogenes and latency-associated transcripts (LATs). Additionally, a bioinformatics pipeline was established to identify circRNAs in other herpesviruses. This study provides important insights into MDV virulence genes and herpesviruses-mediated gene dysregulation.
JOURNAL OF VIROLOGY
(2022)
Article
Virology
Erwan Sallard, Frank Schult, Carolin Baehren, Eleni Buedding, Olivier Mboma, Parviz Ahmad-Nejad, Beniam Ghebremedhin, Anja Ehrhardt, Stefan Wirth, Malik Aydin
Summary: Respiratory viruses play a significant role in exacerbating asthma, and human rhinovirus (HRV) infection is a strong biomarker for exacerbation.
Article
Microbiology
Jana Boddin, Wing-Hang Ip, Britta Wilkens, Konstantin von Stromberg, Wilhelm Ching, Emre Koyuncu, Luca D. Bertzbach, Thomas Dobner
Summary: This study reveals the significant impact of single amino acid exchange mutations in the DNA binding protein of human adenovirus on viral replication. The interactions with the cellular ubiquitination machinery and the formation of viral replication centers are crucial steps that are affected by these mutations. This research has implications for the optimization of adenoviral vectors and the development of anti-adenoviral compounds.
Article
Cell Biology
Raphael L. Tsoukas, Wolfram Volkwein, Jian Gao, Maren Schiwon, Nora Bahlmann, Thomas Dittmar, Claudia Hagedorn, Eric Ehrke-Schulz, Wenli Zhang, Armin Baiker, Anja Ehrhardt
Summary: In this study, the authors systematically analyzed the receptor usage of different adenoviruses using a reporter gene-tagged adenovirus library and a human gene knockout model. They found that some adenoviruses are dependent on the CD46 or CAR receptor, and other receptors or attachment structures may also play a role in adenovirus transduction.
Article
Virology
Nora A. Bahlmann, Raphael L. Tsoukas, Sebastian Erkens, Hongjie Wang, Franziska Jonsson, Malik Aydin, Ella A. Naumova, Andre Lieber, Anja Ehrhardt, Wenli Zhang
Summary: Carcinomas exhibit an upregulation of intercellular junctions that hinder immune response and drug therapy. The interaction between human adenovirus type 3 (Ad3) and Desmoglein 2 (DSG2) leads to a shedding of the binding domain and opening of tight junctions. The JO-4 protein, derived from Ad3, has been shown to enhance antibody therapy and chemotherapy effects. However, our study found that introducing the JO4 mutation to adenoviral vectors did not result in increased transduction in DSG2-high cell lines and weakened effects in DSG2-low cell lines. In fact, the JO4 vectors showed resistance in DSG2-negative cell lines possibly due to the negative effect of the JO4 mutation on the usage of another Ad3 receptor: CD46.
Editorial Material
Virology
Thomas Dobner, Luca D. Bertzbach
Editorial Material
Microbiology
Benedikt B. Kaufer, Mark S. Parcells, Luca D. Bertzbach
Article
Immunology
Sara E. Maloney, Ilham M. Alshiraihi, Amarinder Singh, Ian E. Stewart, Jeffrey Mariner Gonzalez, Mercedes Gonzalez-Juarrero, Bernd Meibohm, Anthony J. Hickey
Summary: Nontuberculous mycobacterial (NTM) pulmonary infections are a global health concern. Traditional systemic therapies often lead to adverse reactions and treatment failure. However, the antibiotic tigecycline has shown efficacy against drug-resistant NTM strains. Inhalation therapies using dry powder aerosols are proposed as an alternative means of delivering tigecycline to overcome its stability and tolerability issues.
Article
Biochemical Research Methods
Luca D. Bertzbach, Marina Kohn, Yu You, Lisa Kossak, Mohammad A. Sabsabi, Ahmed Kheimar, Sonja Haertle, Benedikt B. Kaufer
Summary: Marek's disease virus (MDV) is a highly oncogenic alphaherpesvirus that causes fatal lymphoproliferative disease in chickens by infecting immune cells. This study presents protocols for the isolation, maintenance, and efficient MDV infection of primary chicken lymphocytes and lymphocyte cell lines, facilitating the investigation of key aspects of the MDV life cycle in target cells.
Article
Virology
Wing-Hang Ip, Michael H. Tatham, Steewen Krohne, Julia Gruhne, Michael Melling, Tina Meyer, Britta Gornott, Luca D. Bertzbach, Ronald T. Hay, Estefania Rodriguez, Thomas Dobner
Summary: This study used quantitative SUMO proteomics to analyze the cellular consequences of E1B-55K-mediated host cell modulation and adenovirus infection. The results showed that changes in the SUMOylated proteome could regulate DNA damage response, cell cycle control, chromatin assembly, and gene transcription. Additionally, a SUMO-dependent, ubiquitin-mediated degradation mechanism for some SUMO substrates was identified, suggesting that E1B-55K might use multiple mechanisms to alter restrictive cellular pathways.
JOURNAL OF VIROLOGY
(2023)
Article
Immunology
Xiaoyan Wang, Mario Hetzel, Wenli Zhang, Anja Ehrhardt, Wibke Bayer
Summary: This study evaluated the effects of 40 different types of adenovirus on activation marker expression, cytokine secretion, and CD8(+) T cell proliferation capacity in dendritic cells. The results showed that different adenovirus types had varying effects on activation marker expression and cytokine secretion, with many types significantly impairing CD8(+) T cell proliferation. Additionally, the study found that type I interferons played an important role in mediating the suppression of CD8(+) T cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Microbiology
Ahmed Kheimar, Laetitia Trapp-Fragnet, Andele M. Conradie, Luca D. Bertzbach, Yu You, Mohammad A. Sabsabi, Benedikt B. Kaufer
Summary: The highly expressed human telomerase RNA (hTR) plays a protective role in many cancers, while the viral telomerase RNA (vTR) encoded by the highly oncogenic Marek's disease virus (MDV) is crucial for tumor formation. However, hTR cannot replace the function of vTR, indicating host-specific anti-apoptotic functions of vTR and hTR.
MICROBIOLOGY SPECTRUM
(2023)