The FEBS journal最新文献

{"title":"Diel modulation of perireceptor activity influences olfactory sensitivity in diurnal and nocturnal mosquitoes.","authors":"Tanwee Das De, Julien Pelletier, Satyajeet Gupta, Madhavinadha Prasad Kona, Om P Singh, Rajnikant Dixit, Rickard Ignell, Krishanpal Karmodiya","doi":"10.1111/febs.17418","DOIUrl":"https://doi.org/10.1111/febs.17418","url":null,"abstract":"<p><p>Olfaction and diel-circadian rhythm regulate different behaviors, including host-seeking, feeding, and locomotion, in mosquitoes that are important for their capacity to transmit disease. Diel-rhythmic changes of the odorant-binding proteins (OBPs) in olfactory organs are primarily accountable for olfactory rhythmicity. To better understand the molecular rhythm regulating nocturnal and diurnal behaviors in mosquitoes, we performed a comparative RNA-sequencing study of the peripheral olfactory and brain tissues of female Anopheles culicifacies and Aedes aegypti. Data analysis revealed a significant upregulation of genes encoding: OBPs and xenobiotic-metabolizing enzymes including Cytochrome P450 (CYP450) during photophase in Aedes aegypti and the dusk-transition phase in Anopheles culicifacies, hypothesizing their possible function in the regulation of perireceptor events and olfactory sensitivity. RNA interference studies and application of CYP450 inhibitors, coupled with electroantennographic recordings with Anopheles gambiae and Aedes aegypti, established that CYP450 plays a role in odorant detection and antennal sensitivity. Furthermore, brain tissue transcriptome and RNAi-mediated knockdown revealed that daily temporal modulation of neuronal serine proteases may have a crucial function in olfactory signal transmission, thereby affecting olfactory sensitivity. These findings provide a rationale to further explore the species-specific rhythmic expression pattern of the neuro-olfactory encoded molecular factors, which could pave the way to develop and implement successful mosquito control methods.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of multiple binding sites on microtubule associated protein 2c recognized by dimeric and monomeric 14-3-3ζ.","authors":"Séverine Jansen, Subhash Narasimhan, Paula Cabre Fernandez, Lucia Iľkovičová, Aneta Kozeleková, Kateřina Králová, Jozef Hritz, Lukáš Žídek","doi":"10.1111/febs.17405","DOIUrl":"https://doi.org/10.1111/febs.17405","url":null,"abstract":"<p><p>Microtubule associated protein 2 (MAP2) interacts with the regulatory protein 14-3-3ζ in a cAMP-dependent protein kinase (PKA) phosphorylation dependent manner. Using selective phosphorylation, calorimetry, nuclear magnetic resonance, chemical crosslinking, and X-ray crystallography, we characterized interactions of 14-3-3ζ with various binding regions of MAP2c. Although PKA phosphorylation increases the affinity of MAP2c for 14-3-3ζ in the proline rich region and C-terminal domain, unphosphorylated MAP2c also binds the dimeric 14-3-3ζ via its microtubule binding domain and variable central domain. Monomerization of 14-3-3ζ leads to the loss of affinity for the unphosphorylated residues. In neuroblastoma cell extract, MAP2c is heavily phosphorylated by PKA and the proline kinase ERK2. Although 14-3-3ζ dimer or monomer do not interact with the residues phosphorylated by ERK2, ERK2 phosphorylation of MAP2c in the C-terminal domain reduces the binding of MAP2c to both oligomeric variants of 14-3-3ζ.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and structural characterization of a novel acetyl xylan esterase from Aspergillus oryzae.","authors":"Chihaya Yamada, Tomoe Kato, Yoshihito Shiono, Takuya Koseki, Shinya Fushinobu","doi":"10.1111/febs.17420","DOIUrl":"https://doi.org/10.1111/febs.17420","url":null,"abstract":"<p><p>Acetyl xylan esterase plays a crucial role in the degradation of xylan, the major plant hemicellulose, by liberating acetic acid from the backbone polysaccharides. Acetyl xylan esterase B from Aspergillus oryzae, designated AoAxeB, was biochemically and structurally investigated. The AoAxeB-encoding gene with a native signal peptide was successfully expressed in Pichia pastoris as an active extracellular protein. The purified recombinant protein had pH and temperature optima of 8.0 and 30 °C, respectively, and was stable up to 35 °C. The optimal substrate for hydrolysis by purified recombinant AoAxeB among a panel of α-naphthyl esters was α-naphthyl acetate. Recombinant AoAxeB catalyzed the release of acetic acid from wheat arabinoxylan. The release of acetic acid from wheat arabinoxylan increased synergistically with xylanase addition. No activity was detected for the methyl esters of ferulic, p-coumaric, caffeic, or sinapic acids. The crystal structures of AoAxeB in the apo and succinate complexes were determined at resolutions of 1.75 and 1.90 Å, respectively. Although AoAxeB has been classified in the Esterase_phb family in the ESTerases and alpha/beta-Hydrolase Enzymes and Relatives (ESTHER) database, its structural features partly resemble those of ferulic acid esterase in the FaeC family. Phylogenetic analysis also indicated that AoAxeB is located between the clades of the two families. Docking analysis provided a plausible binding mode for xylotriose substrates acetylated at the 2- or 3-hydroxy position. This study expands the current knowledge of the structures of acetyl xylan esterases and ferulic acid esterases that are required for complete plant biomass degradation.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cysteine S-conjugate sulfoxide β-lyase activity for human ACCS.","authors":"Jinmin Gao, Yueqi Xu, Christopher Yeh, Yike Zou, Yang Hai","doi":"10.1111/febs.17419","DOIUrl":"https://doi.org/10.1111/febs.17419","url":null,"abstract":"<p><p>1-Aminocyclopropane-1-carboxylate synthase (ACCS) catalyzes the conversion of S-adenosyl-methionine to 1-aminocyclopropane-1-carboxylate (ACC), a rate-limiting step in ethylene biosynthesis. A gene encoding a putative ACCS protein was identified in the human genome two decades ago. It has been shown to not exhibit any canonical ACC synthase activity and its true function remains obscure. In this study, through a biochemical profiling approach, we demonstrate that human ACCS possesses cysteine conjugate sulfoxide β-lyase activity. This function is unexpected but reasonable, as it somewhat parallels the activity of ACCS proteins found in non-seed plants. Structure-function relationship study of human ACCS, guided by an AlphaFold2 model, allowed us to identify key active site residues that are important for its β-lyase activity. Our biochemical study of human ACCS also provided insights into the function of other mammalian ACCS homologs.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pinocembrin alleviates renal ischemia-reperfusion injury/unilateral ureteral obstruction (UUO)-generated renal fibrosis by targeting the CYP1B1/ROS/MAPK axis.","authors":"Bang-Hua Zhang, Hui Chen, Rui Yang, Zhengyu Jiang, Shiyu Huang, Zhiyuan Chen, Cheng Liu, Lei Wang, Xiu-Heng Liu","doi":"10.1111/febs.17414","DOIUrl":"https://doi.org/10.1111/febs.17414","url":null,"abstract":"<p><p>In our research, we constructed models of renal ischemia-reperfusion (I/R)-exposed acute kidney injury (AKI) and unilateral ureteral obstruction (UUO)-stimulated renal fibrosis (RF) in C57BL/6 mice and HK-2 cells. We firstly authenticated that oral pinocembrin (PIN) administration obviously mitigated tissue damage and renal dysfunction induced by I/R injury, and PIN attenuated UUO-caused RF, as confirmed by the reduced expression of fibrotic markers as well as hematoxylin-eosin (H&E), Sirius red, immunohistochemistry, and Masson staining. Meanwhile, the beneficial role of PIN was again demonstrated in HK-2 cells with hypoxia-reoxygenation (H/R) or transforming growth factor beta-1 (TGF-β1) treatment. Importantly, the \"ingredient-target-pathway-disease\" network was established through bioinformatics analysis and molecular docking, which showed that PIN may target cytochrome P450 1B1 (CYP1B1) and modulate the mitogen-activated protein kinase (MAPK) pathway to exert its impact during injury. Furthermore, experiments confirmed that PIN usage remarkably constrained CYP1B1 expression, reactive oxygen species (ROS) production, MAPK-pathway-associated inflammation, or apoptosis during I/R injury or UUO exposure. PIN also ameliorated the elevated protein phosphorylation of MAPK pathway components [p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase 1 (JNK ERK and JNK)], which validated the PIN-induced inhibition of the MAPK signaling pathway in renal I/R or UUO injury. Moreover, the AAV9 (adeno-associated virus 9)-packed CYP1B1 or pcDNA-CYP1B1 overexpression plasmid was utilized to treat C57BL/6 mice or HK-2 cells to overexpress CYP1B1, respectively. Notably, CYP1B1 overexpression considerably abolished PIN's restriction impact on ROS generation and MAPK pathway activation. In conclusion, via bioinformatics analysis, molecular docking, animal model, and cellular experiments, we proved that PIN alleviates renal I/R injury/UUO-generated renal fibrosis through regulating the CYP1B1/ROS/MAPK axis.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic signatures and network-based methods uncover new senescent cell anti-apoptotic pathways and senolytics.","authors":"Samael Olascoaga, Mina Konigsberg, Jesús Espinal-Enríquez, Hugo Tovar, Félix Matadamas-Martínez, Jaime Pérez-Villanueva, Norma Edith López-Diazguerrero","doi":"10.1111/febs.17402","DOIUrl":"https://doi.org/10.1111/febs.17402","url":null,"abstract":"<p><p>Cellular senescence is an irreversible cell cycle arrest caused by various stressors that damage cells. Over time, senescent cells accumulate and contribute to the progression of multiple age-related degenerative diseases. It is believed that these cells accumulate partly due to their ability to evade programmed cell death through the development and activation of survival and antiapoptotic resistance mechanisms; however, many aspects of how these survival mechanisms develop and activate are still unknown. By analyzing transcriptomic signature profiles generated by the LINCS L1000 project and using network-based methods, we identified various genes that could represent new senescence-related survival mechanisms. Additionally, employing the same methodology, we identified over 600 molecules with potential senolytic activity. Experimental validation of our computational findings confirmed the senolytic activity of Fluorouracil, whose activity would be mediated by a multitarget mechanism, revealing that its targets AURKA, EGFR, IRS1, SMAD4, and KRAS are new senescent cell antiapoptotic pathways (SCAPs). The development of these pathways could depend on the stimulus that induces cellular senescence. The SCAP development and activation mechanisms proposed in this work offer new insights into how senescent cells survive. Identifying new antiapoptotic resistance targets and drugs with potential senolytic activity paves the way for developing new pharmacological therapies to eliminate senescent cells selectively.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein biochemistry and engineering drive the development of a carbonic anhydrase-based carbon dioxide sequestration strategy.","authors":"Loredano Pollegioni, Gianluca Molla","doi":"10.1111/febs.17416","DOIUrl":"https://doi.org/10.1111/febs.17416","url":null,"abstract":"<p><p>The sequestration of carbon dioxide using carbonic anhydrase (CA) is one of the most effective methods for mitigating global warming. The burning of fossil fuels releases large quantities of flue gas; because of its high temperature and of the alkaline conditions required for CaCO₃ precipitation in the mineralization process, thermo-alkali-stable CAs are needed. In this context, Manyumwa et al. conducted a biochemical characterization of three CAs derived from thermophilic bacteria. They then employed a rational design approach to enhance the specific activity and stability of the enzyme from the hydrothermal vent species Persephonella sp. KM09-Lau-8.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects of neutrophil serine protease inhibition against ischemia-reperfusion injury in lung or heart transplantation.","authors":"Sevil Korkmaz-Icöz, Gábor Szabó, Artur Gieldon, Patrick P McDonald, Alexey Dashkevich, Ali Önder Yildirim, Brice Korkmaz","doi":"10.1111/febs.17411","DOIUrl":"https://doi.org/10.1111/febs.17411","url":null,"abstract":"<p><p>Transplanted organs are inevitably exposed to ischemia-reperfusion (IR) injury, which is known to cause graft dysfunction. Functional and structural changes that follow IR tissue injury are mediated by neutrophils through the production of oxygen-derived free radicals, as well as from degranulation which entails the release of proteases and other pro-inflammatory mediators. Neutrophil serine proteases (NSPs) are believed to be the principal triggers of post-ischemic reperfusion damage. Extended preservation times for the transplanted donor organ correlate with heightened occurrences of vascular damage and graft dysfunction. Preservation with α1-antitrypsin, an endogenous inhibitor of NSPs, improves primary graft function after lung or heart transplantation. Furthermore, pre-operative pharmacological targeting of NSP activation in the recipient using chemical inhibitors suppresses neutrophilic inflammation in transplanted organs. Hence, effective control of NSPs in the graft and recipient is a promising strategy to prevent IR injury. In this review, we describe the pathological functions of NSPs in IR injury and discuss their pharmacological inhibition to prevent primary graft dysfunction in lung or heart transplantation.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome-wide alternative mRNA splicing analysis reveals post-transcriptional regulation of neuronal differentiation.","authors":"Yuan Zhou, Sherif Rashad, Kuniyasu Niizuma","doi":"10.1111/febs.17408","DOIUrl":"https://doi.org/10.1111/febs.17408","url":null,"abstract":"<p><p>Alternative splicing (AS) plays an important role in neuronal development, function, and disease. Efforts to analyze the transcriptome of AS in neurons on a wide scale are currently limited. We characterized the transcriptome-wide AS changes in SH-SY5Y neuronal differentiation model, which is widely used to study neuronal function and disorders. Our analysis revealed global changes in five AS programs that drive neuronal differentiation. Motif analysis revealed the contribution of RNA-binding proteins (RBPs) to the regulation of AS during neuronal development. We concentrated on the primary alternative splicing program that occurs during differentiation, specifically on events involving exon skipping (SE). Motif analysis revealed motifs for polypyrimidine tract-binding protein 1 (PTB) and ELAV-like RNA binding protein 1 (HuR/ELAVL1) to be the top enriched in SE events, and their protein levels were downregulated after differentiation. shRNA knockdown of either PTB and HuR was associated with enhanced neuronal differentiation and transcriptome-wide exon skipping events that drive the process of differentiation. At the level of gene expression, we observed only modest changes, indicating predominant post-transcriptional effects of PTB and HuR. We also observed that both RBPs altered cellular responses to oxidative stress, in line with the differentiated phenotype observed after either gene knockdown. Our work characterizes the AS changes in a widely used and important model of neuronal development and neuroscience research and reveals intricate post-transcriptional regulation of neuronal differentiation.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transketolase promotes osteosarcoma progression through the YY1-PAK4 axis.","authors":"Doudou Jing, Wei Wu, Xin Huang, Zhenhao Zhang, Xuanzuo Chen, Fuhua Huang, Jianxiang Liu, Zhicai Zhang, Zengwu Shao, Feifei Pu","doi":"10.1111/febs.17375","DOIUrl":"https://doi.org/10.1111/febs.17375","url":null,"abstract":"<p><p>Osteosarcoma, a malignant bone tumor that occurs in adolescents, proliferates and is prone to pulmonary metastasis. Osteosarcoma is characterized by high genotypic heterogeneity, making it difficult to identify reliable anti-osteosarcoma targets. The genotype of osteosarcoma may be highly dynamic, but its high dependence on energy remains constant. Fortunately, tumors tend to have relatively consistent metabolic types. Targeting metabolism with anti-tumor therapies is a new strategy for treating tumors. Genes related to carbohydrate metabolism are widely and highly expressed in tumor tissues. Transketolase (TKT), a key enzyme at the non-oxidative stage of the pentose phosphate pathway, is up-regulated in various tumors. In the present study, TKT promoted osteosarcoma cell proliferation non-metabolically. Specifically, TKT bound directly to amino acid residues of Yin Yang 1 (YY1) at amino acids 201-228, stimulating YY1 to bind to the promoter of P21 activated kinase 4 (PAK4) and resulting in PAK4 expression and activation of the phosphoinositide 3-kinase-Akt signaling pathway. Additionally, we designed a peptide, YY1-PEP, based on the exact mechanism of how TKT promotes osteosarcoma. Per in vivo and in vitro experiments, YY1-PEP displayed anti-osteosarcoma properties. The present study provides a new feasible strategy against osteosarcoma progression.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}