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)
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
Hang Chen, Rui Yang, Lei Xing, Bin Wang, Dawei Liu, Xiaoqiang Ou, Yumei Deng, Rong Jiang, Junxia Chen
Summary: This study identified a novel hypoxia-induced circRNA, circPFKFB4, and demonstrated its role in promoting breast cancer progression. The study revealed an interaction between circPFKFB4 and the CRL4DDB2 E3 ubiquitin ligase and suggested circPFKFB4 as a potential biomarker and therapeutic target for breast cancer.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Christine R. Langlois, Viola Beier, Ozge Karayel, Jakub Chrustowicz, Dawafuti Sherpa, Matthias Mann, Brenda A. Schulman
Summary: Cells remodel their proteomes to adjust to environmental metabolism demands. The GID E3 ligase regulates the transition from gluconeogenesis to glycolysis, while the Gid10 substrate receptor plays a role in responding to changes in temperature, osmolarity, and nutrient availability, regulating plasma membrane quality control.
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
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
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
Biochemistry & Molecular Biology
Supattra Chaithongyot, Michael Naumann
Summary: STAMBPL1, a deubiquitinylase, plays an important role in cell survival and regulating cell death. This study found that chemotherapeutic agents and Helicobacter pylori can induce the degradation of STAMBPL1, and its interaction with CSN is crucial for its stability and function. Additionally, STAMBPL1 can deubiquitinylate the anti-apoptotic protein Survivin, enhancing cell survival.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biology
Lingyan Wang, Kun Song, Wenzhuo Hao, Yakun Wu, Girish Patil, Fang Hua, Yiwen Sun, Chaoqun Huang, Jerry Ritchey, Clinton Jones, Lin Liu, Jun-Lin Guan, Shitao Li
Summary: FIP200 facilitates RIG-I activation, deficiency of which impairs RIG-I signaling and increases host susceptibility to RNA virus infection. The interaction between FIP200 and RIG-I triggers the innate immune response.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Orsolya Bilkei-Gorzo, Tiaan Heunis, Jose Luis Marin-Rubio, Francesca Romana Cianfanelli, Benjamin Bernard Armando Raymond, Joseph Inns, Daniela Fabrikova, Julien Peltier, Fiona Oakley, Ralf Schmid, Anetta Hartlova, Matthias Trost
Summary: This study reveals the importance of phagosomal ubiquitylation and the E3 ubiquitin ligase RNF115 in regulating innate immune functions during bacterial infections.
Article
Biochemistry & Molecular Biology
Xiaohua Lou, Binbin Ma, Yuan Zhuang, Xiang Xiao, Laurie J. Minze, Junji Xing, Zhiqiang Zhang, Xian C. Li
Summary: Protein ubiquitination is crucial for controlling protein degradation and cell signaling pathways. This study elucidated the crystal structure of TRIM75, a member of the RING E3 ligase family, revealing its tetrameric structure and function.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Chemistry, Medicinal
Adam G. Bond, Conner Craigon, Kwok-Ho Chan, Andrea Testa, Athanasios Karapetsas, Rotimi Fasimoye, Thomas Macartney, J. Julian Blow, Dario R. Alessi, Alessio Ciulli
Summary: This study describes the design and development of a new protein degradation system utilizing a variant of the Brd4 bromodomain as a degradation tag. The system effectively degrades BromoTagged proteins in a fast, selective manner, showing favorable pharmacokinetic profile in mice. This system expands the arsenal of chemical genetic degradation tools for manipulating protein levels and exploring therapeutic potential in cells and in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cell Biology
Martin P. Schwalm, Lena M. Berger, Maximilian N. Meuter, James D. Vasta, Cesear R. Corona, Sandra Roehm, Benedict-Tilman Berger, Frederic Farges, Sebastian M. Beinert, Franziska Preuss, Viktoria Morasch, Vladimir V. Rogov, Sebastian Mathea, Krishna Saxena, Matthew B. Robers, Susanne Mueller, Stefan Knapp
Summary: E3 ligases play a crucial role in regulating protein homeostasis by recruiting substrate proteins to the proteasomal degradation machinery. Recent research has focused on the Baculovirus IAP Repeat (BIR) family of E3 ligases, which contain a structurally conserved but diverse protein interaction domain. The Inhibitors of Apoptosis (IAP) family, which typically have three BIR domains, are promising drug targets. However, there is currently a lack of assay tools to evaluate the selectivity of inhibitors in this target area.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
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)
Review
Biochemistry & Molecular Biology
Rui Zhang, Shaoqing Shi
Summary: HECT-type E3 ubiquitin ligases play a vital role in controlling protein function and stability, and members of the NEDD4 family have critical roles in dysregulation of autophagy in cancer cells. This review focuses on the role of NEDD4 E3 ligases in defective autophagy in cancer cells, discussing their function, substrates, and signaling pathways, providing a basis for cancer treatment through modulation of these ligases.
MOLECULAR MEDICINE
(2023)
Editorial Material
Cell Biology
Yongye Huang, Jianguang Ji, Qi Zhao, Jun Song
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Medicine, General & Internal
Deqiang Zheng, Ning Li, Rui Hou, Xiaoyu Zhang, Lijuan Wu, Jan Sundquist, Kristina Sundquist, Jianguang Ji
Summary: By combining observational and mendelian randomization studies, this research found that the use of GLP-1 RAs significantly decreases the risk of diabetic retinopathy in patients with type 2 diabetes.
Article
Chemistry, Multidisciplinary
Qi Shen, Qiancheng Xiong, Kaifeng Zhou, Qingzhou Feng, Longfei Liu, Taoran Tian, Chunxiang Wu, Yong Xiong, Thomas J. Melia, C. Patrick Lusk, Chenxiang Lin
Summary: The DNA-origami technique is used to construct transmembrane nanopores with programmable size and functionality. By utilizing pneumolysin, a bacterial toxin that forms ring-like channels on cell membranes, hybrid DNA-protein nanopores are formed, enabling the exchange of macromolecules between liposomes and their environment.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Cardiac & Cardiovascular Systems
Jun Xiao, Jianguang Ji, Naiqi Zhang, Xi Yang, Keyuan Chen, Liangwan Chen, Wuqing Huang
Summary: This study assessed the association between genetically predicted lipid traits, their modification through licensed or investigational targets, and heart failure. The results showed a significant relationship between genetically predicted LDL-C, TG, HDL-C, and ApoB levels and heart failure, mainly mediated by coronary heart disease. Drug target analysis identified PCSK9, CETP, and LPL as potential targets for heart failure prevention.
EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY
(2023)
Article
Multidisciplinary Sciences
Yingxia Hu, Ragna B. Gudnadottir, Kirsten M. Knecht, Fidel Arizaga, Stefan R. Jonsson, Yong Xiong
Summary: In this study, the cryo-electron microscopy structure of MVV Vif in complex with CypA and E3 ligase components was reported. The structure, along with biochemical and functional analysis, revealed both conserved and unique structural elements of MVV Vif and its interaction modes with different host proteins. This provides further understanding of the evolutionary relationship between lentiviral Vifs and their mechanisms for capturing host cofactors for immune evasion activities.
Article
Medicine, General & Internal
Yishan Liu, Jan Sundquist, Kristina Sundquist, Deqiang Zheng, Jianguang Ji
Summary: This study examined the long-term impact of childhood cancer on parental mental health, with a focus on potential sex differences between mothers and fathers. The results showed that the mental health of both parents was continuously affected by the diagnosis, but the impact was more severe for mothers. Therefore, tailored psychological services or interventions are necessary to support parents of children with cancer.
Article
Cardiac & Cardiovascular Systems
Ning Li, Xiaoyu Zhang, Meng Zhang, Lijuan Wu, Changwei Li, Yuesong Pan, Wei Wang, Jianguang Ji, Deqiang Zheng
Summary: This study used Mendelian randomization analysis to investigate the association between dyslipidemia and diabetic retinopathy (DR). The findings suggest a negative association between high-density lipoprotein cholesterol (HDL-C) levels and the development of DR, while CETP inhibitors were not found to be associated with DR. These results indicate a potential protective role of HDL-C in preventing DR.
Correction
Biochemistry & Molecular Biology
Long Han, Qinhui Rao, Renbin Yang, Yue Wang, Pengxin Chai, Yong Xiong, Kai Zhang
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Qi Shen, Qingzhou Feng, Chunxiang Wu, Qiancheng Xiong, Taoran Tian, Shuai Yuan, Jiong Shi, Gregory J. Bedwell, Ran Yang, Christopher Aiken, Alan N. Engelman, C. Patrick Lusk, Chenxiang Lin, Yong Xiong
Summary: Using nuclear pore complex mimics, the authors demonstrate that Nup358 provides a dock for HIV-1 capsid on the cytoplasmic side and Nup153 positions the capsid for NPC entry on the nucleoplasmic side. Nup358 and Nup153 create an affinity gradient to regulate capsid penetration, while Nup62 acts as a final gatekeeper against HIV-1 capsid entry.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Chunxiang Wu, Yong Xiong
Summary: Recent studies have provided new insights into the mechanisms of IP6-mediated HIV-1 capsid assembly. The immature Gag lattice facilitates the incorporation of IP6 into virions, which promotes capsid maturation. Structural analysis of capsid protein (CA) assemblies has revealed key motifs that act as switches, regulating the conformation of CA pentamers/hexamers and influencing co-factor accessibility.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Oncology
Shan Huang, Nai-Qi Zhang, Chun-Jie Xu, Wu-Qing Huang, Dong-Xue Li, Jun Li, Lin-Li Yao, Kristina Sundquist, Jan Sundquist, Shu-Heng Jiang, Xin Xing, Li-Peng Hu, Zhi-Gang Zhang, Jianguang Ji, Xue-Li Zhang
Summary: Combined administration of dipyridamole and aspirin enhances the anti-cancer effect of aspirin against colorectal cancer by inducing endoplasmic reticulum stress and apoptosis.
Letter
Urology & Nephrology
Kari Hemminki, Jianguang Ji, Jan Sundquist
Meeting Abstract
Biophysics
Daisy Duan, Wanqing Lyu, Kuanlin Wu, Chunxiang Wu, Yong Xiong, Anthony J. Koleske
BIOPHYSICAL JOURNAL
(2023)
Article
Public, Environmental & Occupational Health
Yuying Wang, Yujie Zhang, Meng Zhang, Xiaoyu Zhang, Haibin Li, Youxin Wang, Wei Wang, Jianguang Ji, Lijuan Wu, Deqiang Zheng
Summary: This study aimed to explore the prevalence of adverse reactions to COVID-19 vaccination and provide direct evidence of vaccine safety for the elderly and those with underlying medical conditions. The prevalence of adverse reactions in these populations was found to be similar to that of the general population, suggesting that vaccination is safe for them.
JOURNAL OF INFECTION AND PUBLIC HEALTH
(2023)
Article
Medicine, General & Internal
Naiqi Zhang, Yanni Li, Jan Sundquist, Kristina Sundquist, Jianguang Ji
Summary: This study identified eight druggable target genes for breast cancer and suggested that raloxifene is an effective chemoprevention against breast cancer, using Mendelian randomization analysis and population-based validation.
