FEBS Letters最新文献_第3页

Structure-based identification of herbacetin and caffeic acid phenethyl ester as inhibitors of S-adenosylmethionine-dependent viral methyltransferase. 基于结构的草菌素和咖啡酸苯乙酯作为s -腺苷甲硫氨酸依赖性病毒甲基转移酶抑制剂的鉴定。

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-05-12 DOI: 10.1002/1873-3468.70054

Mandar Bhutkar, Amith Kumar, Ruchi Rani, Vishakha Singh, Ankita Saha, Akashjyoti Pathak, Aditi Kothiala, Supreeti Mahajan, Bhairavnath Waghmode, Shalja Verma, Ravi Kumar, Rajat Mudgal, Debabrata Sircar, Pravindra Kumar, Shailly Tomar

{"title":"Structure-based identification of herbacetin and caffeic acid phenethyl ester as inhibitors of S-adenosylmethionine-dependent viral methyltransferase.","authors":"Mandar Bhutkar, Amith Kumar, Ruchi Rani, Vishakha Singh, Ankita Saha, Akashjyoti Pathak, Aditi Kothiala, Supreeti Mahajan, Bhairavnath Waghmode, Shalja Verma, Ravi Kumar, Rajat Mudgal, Debabrata Sircar, Pravindra Kumar, Shailly Tomar","doi":"10.1002/1873-3468.70054","DOIUrl":"https://doi.org/10.1002/1873-3468.70054","url":null,"abstract":"Chikungunya (CHIKV) and dengue (DENV) viruses pose a public health risk and lack antiviral treatments. Structure-based molecular docking of a natural MTase substrates library identified herbacetin (HC) and caffeic acid phenethyl ester (CAPE) as potential CHIKV nsP1 and DENV NS5 MTase inhibitors. Binding affinities and MTase inhibition were confirmed using purified proteins. The crystal structure of DENV 3 NS5 MTase and CAPE complex revealed CAPE binding at viral RNA capping sites. Interestingly, HC and CAPE depleted polyamines crucial for RNA virus replication and decreased viral titer with IC50 values of ~ 13.44 and ~ 0.57 μm against CHIKV, and ~ 7.24 and ~ 1.01 μm against DENV 3, respectively. Polyamine addition did not reverse the antiviral effects, suggesting a dual inhibition mechanism. Impact statement This study reveals the antiviral potential of natural small molecules, Herbacetin (HC) and Caffeic acid phenethyl ester (CAPE) against Dengue and Chikungunya viruses. The molecules deplete polyamine levels and directly inhibit viral methyltransferases. This study opens new avenues for developing antiviral strategies that target both host factors and viral components.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A stepwise emergence of evolution in the RNA world. RNA世界中逐步出现的进化。

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-05-12 DOI: 10.1002/1873-3468.70065

Philippe Nghe

{"title":"A stepwise emergence of evolution in the RNA world.","authors":"Philippe Nghe","doi":"10.1002/1873-3468.70065","DOIUrl":"https://doi.org/10.1002/1873-3468.70065","url":null,"abstract":"Building on experimental evidence and replicator theories, I propose a 3-stage scenario for a transition from autocatalysis into template-based replication of RNA, providing a pathway for the origin of life. In stage 1, self-reproduction occurs via autocatalysis using oligomer substrates, replicator viability relies on substrate-specificity, and heritable variations are mediated by structural interactions. In stage 2, autocatalysis coexists with the templated ligation of external substrates. This dual mode of reproduction combined with limited diffusion avoids the error catastrophe. In stage 3, template-based replication takes over and uses substrates of decreasing size, made possible by enhanced catalytic properties and compartmentalization. Structural complexity, catalytic efficiency, metabolic efficiency, and cellularization all evolve gradually and interdependently, ultimately leading to evolutionary processes similar to extant biology. Impact statement This perspective proposes a testable stepwise scenario for the emergence of evolution in an RNA origin of life. It shows how evolution could appear in a gradual manner, thanks to catalytic feedback among random mixtures of molecules. It highlights possible couplings between the different facets of molecular self-organization, which could bootstrap life.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interferon-induced protein ISG15 in the central nervous system, quo vadis? 干扰素诱导的ISG15蛋白在中枢神经系统中的作用

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-05-12 DOI: 10.1002/1873-3468.70063

Adam M Glass, Sonia Navas-Martin

{"title":"Interferon-induced protein ISG15 in the central nervous system, quo vadis?","authors":"Adam M Glass, Sonia Navas-Martin","doi":"10.1002/1873-3468.70063","DOIUrl":"https://doi.org/10.1002/1873-3468.70063","url":null,"abstract":"The ubiquitin-like interferon (IFN)-stimulated gene 15 (ISG15) is a unique molecular effector that functions both intra- and extracellularly. Central to its pleiotropic nature is the ability to coordinate cellular responses following its conjugation to target proteins via ISGylation or in its free form. The activity of ISG15 is highly context-dependent: in the case of viral infections, ISG15 can serve as a pro- or antiviral factor. While ISG15 has been studied extensively, several gaps persist in our understanding of its role in dysregulated immune homeostasis. In particular, the role of ISG15 in the central nervous system (CNS), which has traditionally been considered an immune-privileged site, remains ill-defined. Interestingly, elevated ISG15 expression is observed in the CNS following instances of brain injury, autoimmunity, neurodegeneration, and viral infection. In this review, we seek to provide a comprehensive analysis of these studies as they pertain to ISG15 and its potential roles in the CNS. Furthermore, we discuss questions and challenges in the field while highlighting ISG15 as a potential diagnostic biomarker or therapeutic target. Impact statement While ISG15 has been studied extensively, several gaps remain in our understanding of its role in dysregulated immune homeostasis and its impact within the central nervous system (CNS). In this review, we provide a comprehensive analysis of the emerging roles of ISG15 in brain injury, autoimmunity, neurodegeneration, and viral infection within the CNS.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ion channel function of polycystin-2/polycystin-1 heteromer revealed by structure-guided mutagenesis. 结构引导诱变揭示多囊蛋白2/多囊蛋白1异构体的离子通道功能。

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-05-12 DOI: 10.1002/1873-3468.70059

Tobias Staudner, Juthamas Khamseekaew, M Gregor Madej, Linda Geiges, Bardha Azemi, Christine Ziegler, Christoph Korbmacher, Alexandr V Ilyaskin

引用次数: 0

Decoding the dual role of autophagy in cancer through transcriptional and epigenetic regulation. 通过转录和表观遗传调控解码自噬在癌症中的双重作用。

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-05-09 DOI: 10.1002/1873-3468.70060

Young Suk Yu, Ik Soo Kim, Sung Hee Baek

{"title":"Decoding the dual role of autophagy in cancer through transcriptional and epigenetic regulation.","authors":"Young Suk Yu, Ik Soo Kim, Sung Hee Baek","doi":"10.1002/1873-3468.70060","DOIUrl":"https://doi.org/10.1002/1873-3468.70060","url":null,"abstract":"Autophagy is a conserved catabolic process that is essential for maintaining cellular homeostasis by degrading and recycling damaged organelles and misfolded proteins. In cancer, autophagy exhibits a context-dependent dual role: In early stages, autophagy acts as a tumor suppressor by preserving genomic integrity and limiting oxidative stress. In advanced stages, autophagy supports tumor progression by facilitating metabolic adaptation, therapy resistance, immune evasion, and metastasis. This review highlights the molecular mechanisms underlying this dual function and focuses on the transcriptional and epigenetic regulation of autophagy in cancer cells. Key transcription factors, including the MiT/TFE family, FOXO family, and p53, as well as additional regulators, are discussed in the context of stress-responsive pathways mediated by mTORC1 and AMPK. A deeper understanding of the transcriptional and epigenetic regulation of autophagy in cancer is crucial for developing context-specific therapeutic strategies to either promote or inhibit autophagy depending on the cancer stage, thereby improving clinical outcomes in cancer treatment.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Autophagy in cancer and protein conformational disorders. 癌症中的自噬和蛋白质构象紊乱。

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-05-08 DOI: 10.1002/1873-3468.70061

Sergio Attanasio

引用次数: 0

Modifications in FLAP's second cytosolic loop influence 5-LOX interaction, inhibitor binding, and leukotriene formation. FLAP第二细胞质环的修饰影响5-LOX相互作用、抑制剂结合和白三烯形成。

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-05-08 DOI: 10.1002/1873-3468.70066

Erik Romp, Katharina Rataj, Stefanie König, Marcia E Newcomer, Oliver Werz, Ulrike Garscha

引用次数: 0

Lytic photoreceptor cell death caused by Rab escort protein deficiency in Drosophila. 拉布护卫蛋白缺乏引起果蝇裂解性光感受器细胞死亡。

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-05-05 DOI: 10.1002/1873-3468.70056

Shogo Sasaki, Rina Satoh, Takunori Satoh, Akiko K Satoh

{"title":"Lytic photoreceptor cell death caused by Rab escort protein deficiency in Drosophila.","authors":"Shogo Sasaki, Rina Satoh, Takunori Satoh, Akiko K Satoh","doi":"10.1002/1873-3468.70056","DOIUrl":"https://doi.org/10.1002/1873-3468.70056","url":null,"abstract":"Choroideremia (CHM) is a rare X-linked recessive form of inherited retinal degeneration caused by the deficiency of the Rab escort protein 1 (REP1)-encoding CHM gene. REP1 is essential for the post-translational prenylation of the key players in intracellular membrane trafficking, the Rab GTPases. In this study, we aimed to analyze the mechanisms of retinal degeneration caused by Rep deficiency using the Drosophila retina as a model system. Rab GTPases lost their membrane association ability and diffused into the cytoplasm, and the accumulation of unprenylated Rab6 and Rab7 was observed in Rep-deficient photoreceptors. Notably, Rep-deficient photoreceptors underwent progressive cell death via cell swelling and rupture rather than apoptosis. These findings provide new insight to seek a therapeutic approach to CHM. Impact statement Choroideremia is an inherited retinal degeneration caused by a deficiency of Rab escort protein 1 (Rep-1). We used the Drosophila retina as a model to study the mechanism of retinal degeneration in Rep-deficiency and found that Rep-deficient photoreceptors undergo progressive cell death via cell swelling and rupture rather than apoptosis.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Amy and Friends: improving the lives of individuals affected by DNA repair disorders 艾米和朋友们：改善受DNA修复障碍影响的个体的生活。

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-05-05 DOI: 10.1002/1873-3468.70049

Jayne Hughes, Donata Orioli, Lavinia Arseni

引用次数: 0

Protonophore activity of short-chain fatty acids induces their intracellular accumulation and acidification. 短链脂肪酸的质子团活性诱导其在细胞内积累和酸化。

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-05-05 DOI: 10.1002/1873-3468.70064

Muwei Jiang, Frans Bianchi, Geert van den Bogaart

引用次数: 0