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
Virology
Marie Fiedler, Wing-Hang Ip, Helga Hofmann-Sieber, Britta Wilkens, Francis K. Nkrumah, Wenli Zhang, Anja Ehrhardt, Luca D. Bertzbach, Thomas Dobner
Summary: The human adenovirus type C5 (HAdV-C5) E1B-55K protein is a multifunctional regulator of HAdV-C5 replication, with phosphorylation and SUMO conjugation playing important roles in its functions. The interaction between E1B-55K and E4orf6 inhibits SUMOylation of E1B-55K, which may promote viral replication.
Article
Biochemistry & Molecular Biology
Bing Zhang, Yao Li, Qiqi Feng, Lili Song, Cheng Dong, Xiaojie Yan
Summary: This study elucidates how ZYGG11B recognizes the Nterminus of ORF10, expanding the current understanding of ORF10 interaction with ZYGG11B and potentially inspiring the development of novel therapies for COVID-19.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
J. Wade Harper, Brenda A. Schulman
Summary: Cullin-RING ubiquitin ligases (CRLs) are modular platforms that regulate biological processes by ubiquitylating specific targets. Regulation is achieved through dynamic control of activation and substrate ubiquitylation, and CRLs provide a vast landscape for developing small molecules that reshape interactions and promote targeted turnover of proteins. Ultimately, the dynamics of substrate receptor interchange in CRLs drive the turnover of selected proteins to influence cellular decision-making.
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 90, 2021
(2021)
Article
Biochemistry & Molecular Biology
Sebastian Kostrhon, J. Rajan Prabu, Kheewoong Baek, Daniel Horn-Ghetko, Susanne von Gronau, Maren Kluegel, Jerome Basquin, Arno F. Alpi, Brenda A. Schulman
Summary: The study investigates the cooperation of two distinct E3 ligases, revealing the role of ARIH2 in the ubiquitylation of substrates of neddylated CUL5-RBX2-based E3s. It is found that NEDD8 regulates cullin-specifically by recruiting ARIH family members through allosteric mechanism. Through structural analyses, it is shown how a ubiquitin-like protein induces protein-protein interactions indirectly, offering potential therapeutic targeting opportunities.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Katherine H. Reiter, Alex Zelter, Maria K. Janowska, Michael Riffle, Nicholas Shulman, Brendan X. MacLean, Kaipo Tamura, Matthew C. Chambers, Michael J. MacCoss, Trisha N. Davis, Miklos Guttman, Peter S. Brzovic, Rachel E. Klevit
Summary: This study characterized the interaction between the auto-inhibited RBR ligase HHARI and its substrate 4EHP using a combination of techniques. The results revealed a binding platform on the catalytic domain of HHARI and the role of a phosphomimetic mutation in promoting the release and reorientation of Rcat for substrate modification. These findings identify a direct binding interaction between an RBR ligase and its substrate and propose a general model for substrate recognition.
Article
Biochemistry & Molecular Biology
Dana Harshuk-Shabso, Noam Castel, Ran Israeli, Sheri Harari, Elah Pick
Summary: The study revealed that the yeast CSN possesses a highly conserved cullin deneddylase core complex, and can be utilized for researching CSN deneddylation and testing the efficacy of inhibitors.
Article
Medical Laboratory Technology
Gael K. Scholtes, Aubrey M. Sawyer, Cristina C. Vaca, Isabelle Clerc, Meejeon Roh, Chisu Song, Richard T. D'Aquila
Summary: The A3 family of cytidine deaminases plays a crucial role in DNA repair and cancer development, and is also affected by various viruses. pVHL induces degradation of all 7 A3 proteins through its complex CRLpVHL, identifying specific cellular factors that regulate A3 post-translationally.
TRANSLATIONAL RESEARCH
(2021)
Article
Medicine, Research & Experimental
Yuqiu Wang, Chen Yang, Hanyang Hu, Chen Chen, Mengdi Yan, Feixiang Ling, Kathy Cheng Wang, Xintao Wang, Zhe Deng, Xinyue Zhou, Feixu Zhang, Sen Lin, Zengmin Du, Kai Zhao, Xiao Xiao
Summary: This study reports a novel AAV serotype, AAVzk2, which exhibits strong liver transduction and liver-specific gene delivery, similar to AAV8 and AAV9, with low immunoreactivity like AAV5. This provides a new therapeutic option for individuals who cannot be treated with AAV8 and AAV9.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Biochemical Research Methods
Brian D. Young, Jihui Sha, Ajay A. Vashisht, James A. Wohlschlegel
Summary: This study identified novel regulators of G beta gamma signaling in human cells using mass spectrometry, with KCTD2 and KCTD5 shown to specifically recognize G beta gamma and be involved in downstream signal transduction. These KCTD proteins act as substrate adaptors for a multisubunit CUL3-RING ubiquitin ligase, promoting monoubiquitination of G beta(1/2) lysine-23 and regulating downstream signaling. Depletion of these adaptors impairs downstream signaling in cancer cell lines.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Physiology
Maximillian Fischer, Moritz Jakab, Marc N. N. Hirt, Tessa R. R. Werner, Stefan Engelhardt, Antonio Sarikas
Summary: This study identified 13 novel CRLs that can positively or negatively regulate cardiac hypertrophy. Among them, CRLFbox25 was further characterized as a potential modulator of cardiac hypertrophy.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Food Science & Technology
Xiankui Gao, Xiujuan Li, Chengan Chen, Can Wang, Yuqi Fu, ZiZhen Zheng, Min Shi, Xiaolong Hao, Limei Zhao, Minghua Qiu, Guoyin Kai, Wei Zhou
Summary: This study identified and predicted the structure and function of CULLIN (CUL) genes in Salvia miltiorrhiza through genomewide analysis, and found that CUL genes play important roles in various biological processes such as abscission reaction acid (ABA) processing. Coexpression network analysis suggested that three CUL genes might be involved in the biosynthesis of phenolic acid or tanshinone in S. miltiorrhiza.
CURRENT RESEARCH IN FOOD SCIENCE
(2022)
Article
Developmental Biology
Qingshuang Cai, Jing Yan, Renjie Duan, Yangyang Zhu, Yongzhi Hua, Yongrong Liao, Qingyang Li, Weini Li, Shanming Ji
Summary: The Drosophila ovary has been a well-established system for studying stem cell fate determination mechanisms. Bone morphogenetic protein (BMP) signaling promotes the maintenance of germline stem cells (GSCs) by inhibiting the transcription of the bag-of-marbles (bam) gene. This study reveals that the E3 ligase Cullin-2 (Cul2) is involved in regulating Bam ubiquitination, which is crucial for GSC maintenance and proper germline development.
DEVELOPMENTAL BIOLOGY
(2023)
Article
Immunology
Huiqing Xiu, Yanmei Peng, Xiaofang Huang, Jiali Gong, Jie Yang, Jiachang Cai, Kai Zhang, Wei Cui, Yingying Shen, Jianli Wang, Shufang Zhang, Zhijian Cai, Gensheng Zhang
Summary: Neddylation activation in macrophages plays a critical protective role against MRSA infection by increasing ROS production. Inhibiting neddylation may lead to liver and kidney injury and increased mortality in MRSA infection, suggesting a new non-antibiotic treatment strategy.
JOURNAL OF IMMUNOLOGY
(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)
