Review
Cell Biology
Kamalakshi Deka, Yinghui Li
Summary: The NF-kappa B signaling pathway plays a major role in inflammation and innate immunity, and is also crucial for cancer initiation and progression. It consists of canonical and non-canonical pathways, with the canonical pathway being prevalent in various human malignancies and inflammation-related diseases. The non-canonical pathway is also increasingly recognized in disease pathogenesis.
Review
Immunology
Timothy C. Borbet, Marcus J. Hines, Sergei B. Koralov
Summary: B lymphocytes play a central role in host immune defense, and their development and function are regulated by miRNAs. Studies have found that miRNAs are crucial for B cell development in the bone marrow and their subsequent population of the peripheral immune system, preventing autoimmunity by regulating downstream signaling of the B cell antigen receptor.
IMMUNOLOGICAL REVIEWS
(2021)
Article
Nutrition & Dietetics
Xiaoxuan Guo, Jing Qiu, Yongzhong Qian
Summary: 6-Shogaol exhibited preventive effects on sepsis-induced liver injury by inhibiting inflammatory pathways and oxidative enzyme damage, as confirmed by transcriptomic analysis. Overlapping genes related to inflammation pathways were identified in different treatment groups, indicating the potential mechanism of action for 6-shogaol in treating liver disorders associated with sepsis.
Article
Multidisciplinary Sciences
I. Cody MacDonald, Travis R. Seamons, Jonathan C. Emmons, Shwan B. Javdan, Tara L. Deans
Summary: Expansion of genetic toolkits for prokaryotic synthetic biology can enhance gene expression dynamics. Integrating the eukaryotic transcription factor QF into E. coli allows for the construction of genetic devices with complex functions.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Maria Josefina Quezada, Pablo Lopez-Bergami
Summary: ROR1 is a receptor for WNT5A and related Wnt proteins, which regulates cell migration, cell polarity, neural patterning, and organogenesis during embryonic development. It transduces signals from Wnt glycoproteins to intracellular Wnt/PCP and Wnt/Ca++ pathways. In addition, it activates multiple signaling pathways in cancer cells, such as PI3K/AKT, MAPK, NF-Kappa B, STAT3, and Hippo pathways. Aberrant expression of ROR1 in cancer is associated with tumor progression and poor survival, making it a potential therapeutic target.
CELLULAR SIGNALLING
(2023)
Article
Immunology
Mingming Zhao, Prashant Chauhan, Cheryl A. Sherman, Amit Singh, Mary Kaileh, Krystyna Mazan-Mamczarz, Hongkai Ji, Jaimy Joy, Satabdi Nandi, Supriyo De, Yongqing Zhang, Jinshui Fan, Kevin G. Becker, Png Loke, Weiqiang Zhou, Ranjan Sen
Summary: Sen et al. conducted in-depth temporal multi-omic analyses to investigate the selective functions of Rel and RelA in B cells upon B cell receptor (BCR) activation. They identified distinct kinetic patterns of gene expression mediated by RelA and Rel, and revealed functional antagonism between these closely related NF-& kappa;B subunits.
Review
Biochemistry & Molecular Biology
Li Tao, Xiaomeng Ren, Wenhui Zhai, Zheng Chen
Summary: The non-canonical NF-kappa B signaling pathway plays a crucial role in liver diseases by regulating liver homeostasis and participating in various pathological processes. Small-molecule inhibitors targeting this pathway have shown potential in the treatment of liver injuries.
Article
Biochemistry & Molecular Biology
Pei-Wei Weng, Vijesh Kumar Yadav, Narpati Wesa Pikatan, Iat-Hang Fong, I-Hsin Lin, Chi-Tai Yeh, Wei-Hwa Lee
Summary: Our research demonstrated that in osteoarthritis, activated human chondrocytes (AC) show elevated expression of NF kappa B, TNF-alpha, IL-6, and miR-21 compared to healthy chondrocytes (HC). AC induced apoptosis in HC and inhibited the expression of chondrogenesis inducers. The study revealed the role of the NF kappa B/miR-21 axis in OA progression, and the therapeutic potential of SC75741 as an inhibitor of miR-21/NF kappa B-driven OA progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Karolina Nowak, Ewa Jablonska, Marzena Garley, Piotr Radziwon, Wioletta Ratajczak-Wrona
Summary: The study found that MeP modulated the expression of ER alpha, activated the NF-kappa B pathway while being inhibited by ERs, decreased NO production, and did not influence IL-8 secretion.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2021)
Article
Plant Sciences
Jung A. Lee, Ju Young Shin, Seong Su Hong, Young-Rak Cho, Ju-Hyoung Park, Dong-Wan Seo, Joa Sub Oh, Jae-Shin Kang, Jae Ho Lee, Eun-Kyung Ahn
Summary: Tetracera loureiri is a woody climber found in open deciduous or evergreen forests in Southeast Asia, and its ethanol extract ETL has been shown to inhibit nitric oxide production, reduce expression of pro-inflammatory mediators, and downregulate NF-kappa B and MAPK signaling pathways in LPS-induced macrophages, indicating its potential therapeutic value for inflammatory diseases.
Article
Biotechnology & Applied Microbiology
Xiaojie Lu, Yue Jing, Xiaofei Zhou, Naisheng Zhang, Jiandong Tai, Yongguo Cao
Summary: Bacillus licheniformis Zhengchangsheng (R) has been shown to inhibit obesity by regulating gut microbiota in obese mice, leading to improved body weight, fat accumulation, serum lipid profiles, inflammatory cytokines, and glucose and lipid metabolism. Additionally, it activates the AMP-activated protein kinase pathway, suggesting its potential in treating obesity and related metabolic diseases.
PROBIOTICS AND ANTIMICROBIAL PROTEINS
(2021)
Article
Biochemistry & Molecular Biology
German A. Arenas, Jose G. Valenzuela, Estefania Penaloza, Adolfo A. Paz, Rodrigo Iturriaga, Claudia G. Saez, Bernardo J. Krause
Summary: This study found that altered shear stress patterns affect the expression of PIEZO1 and mechanosensitive-related genes in endothelial cells, resulting in an inflammatory response. Activation of NF-kappa B via p65 signaling pathway regulates PIEZO1 expression, providing a new molecular link between prooxidant and inflammatory responses and mechanosensitive pathways in the endothelium.
Article
Geriatrics & Gerontology
Weihua Jin, Fen Chen, Qiufu Fang, Genxiang Mao, Yizhong Bao
Summary: Osteoporosis is a systemic bone degenerative disease characterized by low bone mass and deteriorated bone microarchitecture. Glycans known as Gs have been found to inhibit osteoclast generation and exert anti-osteoporosis effects by modulating the IRF-8 signaling pathway.
EXPERIMENTAL GERONTOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Christian Bailly
Summary: Sesquiterpene lactones (SLs) are abundant and bioactive compounds in plants, with britannin (BRT) being a pseudoguaianolide-type SL that exhibits significant anticancer activities through mechanisms such as interference with pathways, blockade of signaling, and modulation of immune responses. BRT's reactivity with proteins and potential options to reduce this reactivity are discussed, emphasizing its ability to modulate the tumor microenvironment and immune responses. The review also highlights the implications of the PD1/PD-L1 checkpoint in BRT's anticancer action.
Article
Immunology
Lu Yao, Yanjun Gu, Tianyi Jiang, Huilian Che
Summary: This study found that activating PPAR-gamma can alleviate clinical symptoms and immune reactions in food allergies. Activation of PPAR-gamma can mitigate food allergies by enhancing intestinal mucosal integrity and tight junctions, and inhibiting mast cell degranulation. Furthermore, PPAR-gamma activation can also inhibit PAK1 phosphorylation and p65 expression.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Evgenia N. Nikolova, Robyn L. Stanfield, H. Jane Dyson, Peter E. Wright
Article
Biochemistry & Molecular Biology
Tadateru Nishikawa, Jonathan M. Wojciak, H. Jane Dyson, Peter E. Wright
Article
Biophysics
Amrinder Singh, H. Jane Dyson
Summary: NF-kappa B is a family of transcription factors that modulate gene expression by recognizing DNA elements. This study provides complete backbone and side chain resonance assignments for the p50 homodimer, serving as a basis for understanding its interaction with DNA.
BIOMOLECULAR NMR ASSIGNMENTS
(2021)
Article
Multidisciplinary Sciences
Xun Sun, H. Jane Dyson, Peter E. Wright
Summary: The phosphorylation of Thr55 modulates DNA binding of p53, controlling both activation and termination of p53-mediated transcriptional programs during different stages of the cellular DNA damage response.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
James A. Ferguson, Xun Sun, H. Jane Dyson, Peter E. Wright
Summary: This study used F-19 nuclear magnetic resonance to investigate the impact of pathogenic mutations on the aggregation kinetics and stability of both the TTR tetramer and monomer. The findings revealed that certain mutations destabilize TTR and promote aggregation, while others disrupt a Schellman helix C-capping motif and increase the monomer's aggregation rate. These insights shed light on how subtle mutations affecting tetramer or monomer stability can drive TTR into the dissociation-aggregation pathway.
Article
Biochemistry & Molecular Biology
H. Jane Dyson
Summary: Advances in isotopic labeling of proteins in the 1980s allowed for pulse sequences to be applied in multidimensional NMR experiments, enabling per-residue information about local relaxation times. This paved the way for experimental determination of backbone dynamics of proteins, leading to an increase in biological insights obtained from such measurements over the past 30 years.
Article
Biochemistry & Molecular Biology
Amrinder Singh, R. Bryn Fenwick, H. Jane Dyson, Peter E. Wright
Summary: Conformational fluctuations from ground-state to excited states play a key role in enzyme catalysis, with the release of NADP(+) in E. coli DHFR being studied through relaxation dispersion analysis. A dynamic knockout mutant unable to access occluded conformations revealed two excited states, one related to fluctuations near the active site and the other to motions within the binding site consistent with disorder observed in a mutant protein. These studies highlight the detailed kinetic information that can be obtained from relaxation dispersion experiments to understand small changes in catalytic mechanism.
Article
Biochemistry & Molecular Biology
Francis D. Appling, Rebecca B. Berlow, Robyn L. Stanfield, H. Jane Dyson, Peter E. Wright
Summary: This study reveals how CITED2 efficiently downregulates the hypoxic response by nearly mutually exclusively binding to the TAZ1:HIF-1a complex through negative cooperativity. Insights into the molecular determinants of facilitated dissociation are obtained through modeling the ternary intermediate and structural studies of a fusion peptide complex.
Article
Biochemistry & Molecular Biology
Michael W. Risor, Ariane L. Jansma, Natasha Medici, Brittany Thomas, H. Jane Dyson, Peter E. Wright
Summary: The N-terminal region of the HPV16 E7 protein interacts with cellular factors and causes oncogenic transformation of host cells; despite high nanomolar affinity with TAZ2, the complex is disordered and highly dynamic; the fuzzy nature of the complex reflects the promiscuous binding repertoire of viral proteins.
Article
Biochemistry & Molecular Biology
H. Jane Dyson, Peter E. Wright
Summary: Nuclear magnetic resonance (NMR) has been crucial in the study of intrinsically disordered proteins (IDPs) and regions (IDRs), providing valuable insights when combined with other biophysical methods. Recent advancements have been made in studying proteins with both ordered and disordered domains, as well as problematic sequences with repeated amino acid tracts. Innovative applications of NMR have offered new insights into protein aggregation mechanisms and interactions of disordered proteins with their targets. NMR remains invaluable in understanding the structural ensembles, dynamic behavior, and functional mechanisms of IDPs and IDRs.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Rebecca B. Berlow, H. Jane Dyson, Peter E. Wright
Summary: Intrinsically disordered proteins compete for binding to common regulatory targets to carry out their biological functions. The activation domains of HIF-1 alpha and CITED2 function as a unidirectional, allosteric molecular switch to control transcription of adaptive genes. The mechanistic details of this molecular switch were characterized through NMR spectroscopy and biophysical methods, revealing the contributions of individual binding motifs in CITED2. These findings provide insight into the complexity of molecular interactions involving disordered proteins and how they compete for occupancy of common targets.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Alexander S. Krois, Sangho Park, Maria A. Martinez-Yamout, H. Jane Dyson, Peter E. Wright
Summary: The structure and interactions of the C-terminal region of p53 protein have been studied. Full-length p53 constructs were generated using trans-intein splicing and isotopically labeled for NMR analysis. This study provides high-resolution insights into the behavior of the C-terminal domains within the full-length protein and the molecular basis of its interactions with DNA.
Article
Chemistry, Physical
Derrick W. Meinhold, Daniel J. Felitsky, H. Jane Dyson, Peter E. Wright
Summary: The early events in protein folding, especially in the unfolded state, are not well understood. The study used NMR experiments to investigate the transient local collapse events in the unfolded-state of apomyoglobin. The findings suggest that there are pH-dependent transient intramolecular contacts occurring at a microsecond to millisecond time scale. The rapid and concomitant chain collapse and secondary structure formation were observed in the early folding intermediates.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Review
Chemistry, Multidisciplinary
H. Jane Dyson, Peter E. Wright
Summary: It is difficult to assess the role of individual mentors in the development of important ideas. However, in the case of the realization that proteins can be functional without stable folding, the influence of Richard Lerner and the collaborative work in the 1980s on immunogenic peptides provided a foundation for understanding the nature of polypeptides in water solutions. This led to the formulation and development of the concept of intrinsic disorder in proteins, and the recognition of its functional advantage in cellular processes.
ISRAEL JOURNAL OF CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Jeanette R. McConnell, H. Jane Dyson, Shelli R. McAlpine
Summary: This study reveals the interaction between Hsp90 protein and various inhibitors and modulators, showing their binding sites within different functional domains of the protein.
RSC MEDICINAL CHEMISTRY
(2021)
