Nuclear transport proteins: structure, function, and disease relevance

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Ноя. 10, 2023

Abstract Proper subcellular localization is crucial for the functioning of biomacromolecules, including proteins and RNAs. Nuclear transport a fundamental cellular process that regulates many macromolecules within nuclear or cytoplasmic compartments. In humans, approximately 60 are involved in transport, nucleoporins form membrane-embedded pore complexes, karyopherins cargoes through these Ran system ensure directed rapid transport. Many play additional essential roles mitosis, biomolecular condensation, gene transcription. Dysregulation linked to major human diseases such as cancer, neurodegenerative diseases, viral infections. Selinexor (KPT-330), an inhibitor targeting export factor XPO1 (also known CRM1), was approved 2019 treat two types blood cancers, dozens clinical trials ongoing. This review summarizes three decades research data this field but focuses on structure function individual from recent studies, providing cutting-edge holistic view role health disease. In-depth knowledge rapidly evolving has potential bring new insights into biology, pathogenic mechanisms, therapeutic approaches.

Язык: Английский

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Tigliane and daphnane diterpenoids from Thymelaeaceae family: chemistry, biological activity, and potential in drug discovery

Journal of Natural Medicines, Год журнала: 2023, Номер 77(4), С. 625 - 643

Опубликована: Июнь 9, 2023

Abstract Tigliane and daphnane diterpenoids are characteristically distributed in plants of the Thymelaeaceae family as well Euphorbiaceae structurally diverse due to presence polyoxygenated functionalities polycyclic skeleton. These known toxic components, while they have been shown exhibit a wide variety biological activities, such anti-cancer, anti-HIV, analgesic activity, attracting attention field natural product drug discovery. This review focuses on naturally occurring tigliane from provides an overview their chemical structure, distribution, isolation, structure determination, synthesis, with prime focus recent findings.

Язык: Английский

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DHODH inhibition represents a therapeutic strategy and improves abiraterone treatment in castration-resistant prostate cancer

Oncogene, Год журнала: 2024, Номер 43(19), С. 1399 - 1410

Опубликована: Март 13, 2024

Язык: Английский

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Highly anticipated natural diterpenoids as an important source of new drugs in 2013–2023

Chinese Chemical Letters, Год журнала: 2024, Номер 36(1), С. 109955 - 109955

Опубликована: Май 1, 2024

Язык: Английский

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Nuclear Import and Export of YAP and TAZ

Cancers, Год журнала: 2023, Номер 15(20), С. 4956 - 4956

Опубликована: Окт. 12, 2023

Yes-associated Protein (YAP) and its paralog Transcriptional Coactivator with PDZ-binding Motif (TAZ) are major regulators of gene transcription/expression, primarily controlled by the Hippo pathway cytoskeleton. Integrating an array chemical mechanical signals, they impact growth, differentiation, regeneration. Accordingly, also play key roles in tumorigenesis metastasis formation. Their activity is regulated their localization, that is, pathway- and/or cytoskeleton-controlled cytosolic or nuclear sequestration. While many details such prevailing retention models have been elucidated, much less known about actual traffic: import export. Although size not far from cutoff for passive diffusion through pore complex (NPC), do contain any classic localization (NLS) export signal (NES), evidence has accumulating shuttling involves mediated thus regulatable/targetable processes. The aim this review to summarize emerging information/concepts nucleocytoplasmic shuttling, encompassing relevant structural requirements (NLS, NES), transport receptors (NTRs, karyophererins), NPC components, along potential mechanisms regulation. dissecting vs. often challenging, picture suggests YAP/TAZ shuttles across via multiple, non-exclusive, mechanisms, constituting a novel intriguing facet biology.

Язык: Английский

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A natural small molecule alleviates liver fibrosis by targeting apolipoprotein L2

Nature Chemical Biology, Год журнала: 2024, Номер unknown

Опубликована: Авг. 5, 2024

Язык: Английский

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Terpenes and Terpenoids Conjugated with BODIPYs: An Overview of Biological and Chemical Properties

Journal of Natural Products, Год журнала: 2024, Номер 87(4), С. 1306 - 1319

Опубликована: Март 14, 2024

Advancements in small-molecule research have created the need for sensitive techniques to accurately study biological processes living systems. Fluorescent-labeled probes become indispensable tools, particularly those that use boron–dipyrromethene (BODIPY) dyes. Terpenes and terpenoids are organic compounds found nature offer diverse activities, BODIPY-based play a crucial role studying these compounds. Monoterpene–BODIPY conjugates exhibited potential staining bacterial fungal cells. Sesquiterpene–BODIPY derivatives been used sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA), indicating their drug development. Owing unique properties, diterpenes investigated using BODIPY evaluate mechanisms of action. Triterpene–BODIPY synthesized studies, with different spacers affecting cytotoxicity. Fluorescent probes, inspired by terpenoid-containing vitamins, also developed. Derivatives tocopherol, coenzyme Q10, vitamin K1 can provide insights into oxidation–reduction abilities. All applications, including cell membranes investigate immune responses antioxidant properties. Further this field help better understand terpenes various contexts.

Язык: Английский

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A green and simple method for enrichment of major diterpenoids from the buds of Wikstroemia chamaedaphne with macroporous resins and their activation of latent human immunodeficiency virus activity

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 272, С. 132932 - 132932

Опубликована: Июнь 1, 2024

In this study, a green and efficient enrichment method for the four majors active diterpenoid components: pimelotide C, A, simplexin, 6α,7α-epoxy-5β-hydroxy-12-deoxyphorbol-13-decanoate in buds of Wikstroemia chamaedaphne was established using macroporous resin chromatography. The adsorption desorption rates seven resins were compared static tests. D101 exhibited best performance. Static dynamic tests performed to determine purification important bioactive diterpenoids W. chamaedaphne. Diterpenoid extracts obtained by from crude Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis demonstrated that most enriched extracts. These results confirmed could be technology, showed more activation latent human immunodeficiency virus. This study provides novel strategy discovering low-toxicity latency-reversing agents potential basis comprehensive development clinical application

Язык: Английский

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Meroterpenoids from Daphne genkwa shows promising in vitro antitumor activity via inhibiting PI3K/Akt/mTOR signaling pathway in A549 cells

Bioorganic Chemistry, Год журнала: 2023, Номер 140, С. 106803 - 106803

Опубликована: Авг. 23, 2023

Язык: Английский

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Insights of Affinity-Based Probes for Target Identification in Drug Discovery

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер 293, С. 117711 - 117711

Опубликована: Май 6, 2025

Язык: Английский

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