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
Linus V. M. Hopf, Kheewoong Baek, Maren Kluegel, Susanne von Gronau, Yue Xiong, Brenda A. Schulman
Summary: This study reveals the assembly mechanism of CRL7(FBXW)(8) and finds discrepancies with existing models. The results show that CUL7 has an exclusive binding mode with FBXW8 and CRL7 serves as a substrate receptor linked via SKP1-FBXW8 to a neddylated CUL1-RBX1 catalytic module mediating ubiquitination. This finding provides insights into the protective role of CUL7 in human health.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
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
Biochemistry & Molecular Biology
Lukas T. Henneberg, Jaspal Singh, David M. Duda, Kheewoong Baek, David Yanishevski, Peter J. Murray, Matthias Mann, Sachdev S. Sidhu, Brenda A. Schulman
Summary: Researchers have developed conformation-specific antibodies to probe the NEDD8-activated cullin-RING ubiquitin E3 ligase networks in mammalian cells in response to extracellular stimuli, metabolic signals, and degrader drugs.
NATURE CHEMICAL 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
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
Chemistry, Medicinal
Zhang-Xu He, Qi An, Bo Wei, Wen-Juan Zhou, Bing-Fei Wei, Yun-Peng Gong, Xin Zhang, Ge Gao, Guan-Jun Dong, Jin-Ling Huo, Xin-Hui Zhang, Fei-Fei Yang, Hong-Min Liu, Li-Ying Ma, Wen Zhao
Summary: The study revealed that DCN1 was upregulated in isolated cardiac fibroblasts treated with angiotensin II and in mouse hearts after pressure overload. Compound DN-2 specifically targeted DCN1 at molecular and cellular levels and effectively reversed angiotensin II-induced cardiac fibroblast activation.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biotechnology & Applied Microbiology
Iqra Bano, Moolchand Malhi, Min Zhao, Liviu Giurgiulescu, Hira Sajjad, Marek Kieliszek
Summary: Cullin-RING E3 ligases (CRLs) are crucial components of the E3 ubiquitin ligase family, playing essential roles in various diseases, especially in tumor development, with neddylation being identified as an enticing target for anticancer drug discovery. Recent studies have shown significant advancements in protein neddylation, including preclinical and clinical target validation, in the search for neddylation inhibitor compounds.
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
Eric Schulze-Niemand, Michael Naumann
Summary: The COP9 signalosome (CSN) is a universal regulator of Cullin-RING ubiquitin ligases (CRLs) that control cellular processes by degrading signaling proteins. The CSN, with its eight-subunit architecture, inactivates CRLs by removing a small ubiquitin-like modifier called Nedd8. Recent findings on the versatile regulation of CSN-CRL complexes are presented in this review.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Meng-ge Du, Fan Liu, Yan Chang, Shuai Tong, Wei Liu, Yu-jiao Chen, Ping Xie
Summary: Neddylation is a posttranslational modification that plays an important role in regulating protein activity. Smurf1, a ubiquitin ligase, is involved in the neddylation process and interacts with RRP9, a component of the U3 snoRNP complex in pre-rRNA processing. Elevated expression of RRP9 and Smurf1 in colorectal cancer is associated with cancer progression.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Oncology
Yumiao Li, Aiming Zang, Jiejun Fu, Youchao Jia
Summary: Cul7, as a core scaffolding protein, plays crucial roles in cell growth, transformation, and apoptosis, closely associated with the development of tumors. It has the potential to serve as a significant anti-cancer target.
Article
Virology
Elizaveta T. Wick, Colton J. Treadway, Zhijun Li, Nathan Nicely, Zhizhong Ren, Albert S. Baldwin, Yue Xiong, Joseph S. Harrison, Nicholas G. Brown
Summary: Viruses evolve mechanisms to exploit cellular pathways that increase viral fitness, such as enhancing viral replication or evading the host cell immune response. This study reveals how viruses hijack the ubiquitin-proteosome system to target specific host proteins and optimize their binding affinity, allowing them to enhance viral replication and evade the host immune response.
JOURNAL OF VIROLOGY
(2022)
Review
Oncology
M. A. A. Mamun, Ying Liu, Yin-Ping Geng, Yi-Chao Zheng, Ya Gao, Jian-Gang Sun, Long-Fei Zhao, Li-Juan Zhao, Hong-Min Liu
Summary: Neddylation is a process that involves adding NEDD8, a protein, to other molecules in neural precursor cells. This process requires three enzymes: activators (E1), conjugators (E2), and ligators (E3). Recent research has highlighted the importance of two specific enzymes, UBE2M and UBE2F, in neddylation and their potential as targets for developing anti-cancer therapies. This evaluation summarizes the current understanding of the interaction between E2 and E1 or E3, and explores the prospects of using neddylation E2 as a pharmacological target for cancer treatment.
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
Soojung Hahn, Gyuri Kim, Sang-Man Jin, Jae Hyeon Kim
Summary: This study utilized three-dimensional intestinal organoids to investigate the effects of metformin on inflammatory bowel disease (IBD) and found that metformin can enhance intestinal barrier function and reduce levels of inflammatory cytokines.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
V. V. Sudarev, M. S. Gette, S. V. Bazhenov, O. M. Tilinova, E. V. Zinovev, I. V. Manukhov, A. I. Kuklin, Yu. L. Ryzhykau, A. V. Vlasov
Summary: This study investigated the self-assembly processes of ferritin-based protein complexes and obtained structurally characterized oligomeric states. These results provide new potential and opportunities for the application of ferritin in various fields.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Yalda Sabaghi, Farnaz Pourfarzad, Leila Zolghadr, Azita Bahrami, Tahereh Shojazadeh, Alireza Farasat, Nematollah Gheibi
Summary: p-Coumaric acid (p-CA) is a plant compound with anti-cancer activities. This study designed a nano-liposomal carrier containing p-CA to enhance its effectiveness against melanoma cells. The findings showed that the liposomal form of p-CA had a greater impact on the cells. Kinetic modeling indicated that the best fitting model was zero-order.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
M. D. Nazmul Hasan, Md Mahfuzur Rahman, Al Asmaul Husna, Nobuhiro Nozaki, Osamu Yamato, Naoki Miura
Summary: This study investigated the expression of ncRNAs other than miRNAs in different histologic subtypes of canine mammary gland tumors (MGT). Three aberrantly expressed ncRNAs were identified as potential biomarkers for differentiating MGT subtypes. YRNA and tRFs expression levels were found to be decreased in metastatic compared to primary MGT cell lines.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Seine A. Shintani
Summary: In this study, the researchers used signal analysis to study the instantaneous amplitude and phase of sarcomeric oscillations in skeletal muscle. They identified two types of oscillations, sarcomeric oscillations and sarcosynced oscillations, and visualized their behavior during propagating waves. The researchers discovered the presence of sarcomeric defect holes and sarcomeric collision holes, which are important indicators for understanding the oscillation properties of sarcomeres. This finding has important implications for improving our understanding of muscle function and its regulatory mechanisms.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Shuanglin Zhang, Yuzhong Jia, Guolan Ma, Yanyan Yang, Zhenzhen Cao, Antao Luo, Zefu Zhang, Shihan Li, Jie Wen, Hanfeng Liu, Jihua Ma
Summary: Bupleurum is an antiarrhythmic agent that may exert its effects by inhibiting L-type calcium channels.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Tomotaka Ohkubo, Yasuhiko Matsumoto, Hiroaki Sasaki, Kaoru Kinoshita, Yuki Ogasawara, Takashi Sugita
Summary: This study found that Citrobacter koseri inhibits the growth of Staphylococcus epidermidis, disrupting the balance between S. epidermidis and Staphylococcus aureus, and exacerbating inflammation in atopic dermatitis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Toshifumi Asano, Philipp Sasse, Takao Nakata
Summary: A Cre recombination-based fluorescent reporter system was developed to monitor cell-cell fusion. The system successfully detected the formation of multinuclear myotubes and placental syncytiotrophoblast. This tool could facilitate the study of cell-to-cell fusion.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Ke Shi, Yunlong Shan, Xiao Sun, Kuida Chen, Qiong Luo, Qiang Xu
Summary: This study found that low expression of TP53INP2 is associated with poor survival in colorectal cancer (CRC) patients. As the malignancy of CRC progresses, TP53INP2 expression gradually decreases. Knockdown of TP53INP2 promotes CRC cell proliferation and tumor growth. Mechanistically, TP53INP2 deficiency decreases phosphorylation of beta-catenin, leading to increased accumulation and enhanced nuclear translocation and transcriptional activity. Additionally, TP53INP2 sequesters TIM50, inhibiting its activation of beta-catenin. In conclusion, downregulation of TP53INP2 promotes CRC progression by activating beta-catenin.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Martina Rossi, Fabio Tomaselli, Alejandro Hochkoeppler
Summary: Oligomeric enzymes are known for their higher catalytic rates compared to monomeric enzymes, but the extent of additivity in their activity is still not well understood. This study used tetrameric rabbit lactate dehydrogenase as a model to examine the kinetics of its catalytic action. Surprisingly, when the concentration of the limiting reactant exceeded that of a single subunit, there was a significant slowdown in the enzyme's conformational rearrangements.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Amin Sahraei, Mohammad Javad Shamsoddini, Fakhrossadat Mohammadi, Leila Hassani
Summary: This study explored the inhibitory effects of gallium curcumin, indium curcumin, and vanadyl curcumin on the amyloid fibrillation of hen egg white lysozyme, as well as the binding interactions of these metal complexes with the enzyme. The results showed that indium curcumin and vanadyl curcumin exhibited higher binding affinities and stronger inhibitory effects on amyloid fibrillation compared to gallium curcumin.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Takahiro Sasaki, Yoshiki Kuse, Shinsuke Nakamura, Masamitsu Shimazawa
Summary: PGRN deficiency plays a significant role in cardiac remodeling and arrhythmias post-myocardial infarction (MI), potentially by promoting metabolic abnormalities in macrophages.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Hongwei Zhao, Yiqiang Li, Yibo Zhang, Chi Zhang
Summary: Electrical brain stimulation technology is commonly used to treat brain neurological disorders, but it can cause side effects. This study investigated the impact of electric fields on nerve fibers and revealed the possible origin of side effects. The findings provide guidance for selecting electrical parameters in clinical stimulation therapy.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Julia S. Scott, Lake-Ee Quek, Andrew J. Hoy, Johannes V. Swinnen, Zeyad D. Nassar, Lisa M. Butler
Summary: The fatty acid elongation enzyme ELOVL5 plays a critical role in promoting metastasis in prostate cancer. Knocking down ELOVL5 leads to the accumulation of malonyl-CoA, which inhibits fatty acid oxidation in mitochondria. This study highlights the importance of fatty acid elongation in regulating cell viability and provides a potential target for prostate cancer treatment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Zan Zhou, Wen-jun Jiang, Li Li, Jun-qiang Si
Summary: This study investigates the effect of noise exposure on cognitive function in mice and explores the underlying molecular mechanisms. The findings suggest that noise exposure leads to increased inflammation, increased phosphorylation of Tau protein, and decreased levels of postsynaptic density protein, resulting in cognitive impairment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
