The FEBS journal最新文献_第5页

Oxidative stress-induced YAP1 expression is regulated by NCE102, CDA2, and BCS1. 氧化应激诱导的 YAP1 表达受 NCE102、CDA2 和 BCS1 的调控。

The FEBS journal Pub Date : 2024-08-05 DOI: 10.1111/febs.17243

Sarah Takallou, Maryam Hajikarimlou, Mustafa Al-Gafari, Jiashu Wang, Sasi Kumar Jagadeesan, Thomas David Daniel Kazmirchuk, Christina Arnoczki, Houman Moteshareie, Kamaledin B Said, Taha Azad, Martin Holcik, Bahram Samanfar, Myron Smith, Ashkan Golshani

{"title":"Oxidative stress-induced YAP1 expression is regulated by NCE102, CDA2, and BCS1.","authors":"Sarah Takallou, Maryam Hajikarimlou, Mustafa Al-Gafari, Jiashu Wang, Sasi Kumar Jagadeesan, Thomas David Daniel Kazmirchuk, Christina Arnoczki, Houman Moteshareie, Kamaledin B Said, Taha Azad, Martin Holcik, Bahram Samanfar, Myron Smith, Ashkan Golshani","doi":"10.1111/febs.17243","DOIUrl":"https://doi.org/10.1111/febs.17243","url":null,"abstract":"Maintaining cellular homeostasis in the face of stress conditions is vital for the overall well-being of an organism. Reactive oxygen species (ROS) are among the most potent cellular stressors and can disrupt the internal redox balance, giving rise to oxidative stress. Elevated levels of ROS can severely affect biomolecules and have been associated with a range of pathophysiological conditions. In response to oxidative stress, yeast activator protein-1 (Yap1p) undergoes post-translation modification that results in its nuclear accumulation. YAP1 has a key role in oxidative detoxification by promoting transcription of numerous antioxidant genes. In this study, we identified previously undescribed functions for NCE102, CDA2, and BCS1 in YAP1 expression in response to oxidative stress induced by hydrogen peroxide (H2O2). Deletion mutant strains for these candidates demonstrated increased sensitivity to H2O2. Our follow-up investigation linked the activity of these genes to YAP1 expression at the level of translation. Under oxidative stress, global cap-dependent translation is inhibited, prompting stress-responsive genes like YAP1 to employ alternative modes of translation. We provide evidence that NCE102, CDA2, and BCS1 contribute to cap-independent translation of YAP1 under oxidative stress.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141895154","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}

引用次数: 0

The role of the gut microbiota in regulating responses to vaccination: current knowledge and future directions. 肠道微生物群在调节疫苗接种反应中的作用：现有知识和未来方向。

The FEBS journal Pub Date : 2024-08-05 DOI: 10.1111/febs.17241

Charné Rossouw, Feargal J Ryan, David J Lynn

引用次数: 0

Endolysosomal channel TMEM175 mediates antitoxin activity of DABMA 内溶酶体通道 TMEM175 介导了 DABMA 的抗毒素活性。

The FEBS journal Pub Date : 2024-08-04 DOI: 10.1111/febs.17242

Yu Wu, Jiamin Huang, Fei Zhang, Florence Guivel-Benhassine, Mathieu Hubert, Olivier Schwartz, Weihua Xiao, Jean-Christophe Cintrat, Lili Qu, Julien Barbier, Daniel Gillet, Chunlei Cang

{"title":"Endolysosomal channel TMEM175 mediates antitoxin activity of DABMA","authors":"Yu Wu, Jiamin Huang, Fei Zhang, Florence Guivel-Benhassine, Mathieu Hubert, Olivier Schwartz, Weihua Xiao, Jean-Christophe Cintrat, Lili Qu, Julien Barbier, Daniel Gillet, Chunlei Cang","doi":"10.1111/febs.17242","DOIUrl":"10.1111/febs.17242","url":null,"abstract":"DABMA is a chemical molecule optimized from the parent compound ABMA and exhibits broad-spectrum antipathogenic activity by modulating the host's endolysosomal and autophagic pathways. Both DABMA and ABMA inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a cellular assay, which further expands their anti-pathogen spectrum in vitro. However, their precise mechanism of action has not yet been resolved. TMEM175 is a newly characterized endolysosomal channel which plays an essential role in the homeostasis of endosomes and lysosomes as well as organelle fusion. Here, we show that DABMA increases the endosomal TMEM175 current through organelle patch clamping with an EC50 of 17.9 μm. Depletion of TMEM175 protein significantly decreases the antitoxin activity of DABMA and affects its action on acidic- and Rab7-positive endosomes as well as on endolysosomal trafficking. Thus, TMEM175 is necessary for DABMA's activity and may represent a druggable target for the development of anti-infective drugs. Moreover, DABMA, as an activator of the TMEM175 channel, may be useful for the in-depth characterization of the physiological and pathological roles of this endolysosomal channel.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891456","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}

引用次数: 0

Therapeutic targeting of TGF-β in lung cancer. 肺癌中 TGF-β 的治疗靶点。

The FEBS journal Pub Date : 2024-07-31 DOI: 10.1111/febs.17234

Sajjad Aftabi, Amir Barzegar Behrooz, Marco Cordani, Niloufar Rahiman, Mohammadamin Sadeghdoust, Farnaz Aligolighasemabadi, Stephen Pistorius, Seyedeh Hoda Alavizadeh, Nima Taefehshokr, Saeid Ghavami

{"title":"Therapeutic targeting of TGF-β in lung cancer.","authors":"Sajjad Aftabi, Amir Barzegar Behrooz, Marco Cordani, Niloufar Rahiman, Mohammadamin Sadeghdoust, Farnaz Aligolighasemabadi, Stephen Pistorius, Seyedeh Hoda Alavizadeh, Nima Taefehshokr, Saeid Ghavami","doi":"10.1111/febs.17234","DOIUrl":"https://doi.org/10.1111/febs.17234","url":null,"abstract":"Transforming growth factor-β (TGF-β) plays a complex role in lung cancer pathophysiology, initially acting as a tumor suppressor by inhibiting early-stage tumor growth. However, its role evolves in the advanced stages of the disease, where it contributes to tumor progression not by directly promoting cell proliferation but by enhancing epithelial-mesenchymal transition (EMT) and creating a conducive tumor microenvironment. While EMT is typically associated with enhanced migratory and invasive capabilities rather than proliferation per se, TGF-β's influence on this process facilitates the complex dynamics of tumor metastasis. Additionally, TGF-β impacts the tumor microenvironment by interacting with immune cells, a process influenced by genetic and epigenetic changes within tumor cells. This interaction highlights its role in immune evasion and chemoresistance, further complicating lung cancer therapy. This review provides a critical overview of recent findings on TGF-β's involvement in lung cancer, its contribution to chemoresistance, and its modulation of the immune response. Despite the considerable challenges encountered in clinical trials and the development of new treatments targeting the TGF-β pathway, this review highlights the necessity for continued, in-depth investigation into the roles of TGF-β. A deeper comprehension of these roles may lead to novel, targeted therapies for lung cancer. Despite the intricate behavior of TGF-β signaling in tumors and previous challenges, further research could yield innovative treatment strategies.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861992","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}

引用次数: 0

Interconnected microbiomes-insights and innovations in female urogenital health. 相互关联的微生物组--女性泌尿生殖健康的启示与创新。

The FEBS journal Pub Date : 2024-07-30 DOI: 10.1111/febs.17235

Kait F Al, Josh Parris, Kathleen Engelbrecht, Gregor Reid, Jeremy P Burton

引用次数: 0

Corynebacterium glutamicum pyruvate:quinone oxidoreductase: an enigmatic metabolic enzyme with unusual structural features. 谷氨酸棒杆菌丙酮酸：醌氧化还原酶：一种具有不寻常结构特征的神秘代谢酶。

The FEBS journal Pub Date : 2024-07-30 DOI: 10.1111/febs.17232

Cristiano da Silva Lameira, Sini Münßinger, Lu Yang, Bernhard J Eikmanns, Marco Bellinzoni

{"title":"Corynebacterium glutamicum pyruvate:quinone oxidoreductase: an enigmatic metabolic enzyme with unusual structural features.","authors":"Cristiano da Silva Lameira, Sini Münßinger, Lu Yang, Bernhard J Eikmanns, Marco Bellinzoni","doi":"10.1111/febs.17232","DOIUrl":"https://doi.org/10.1111/febs.17232","url":null,"abstract":"Pyruvate:quinone oxidoreductase (PQO) is a flavin-containing peripheral membrane enzyme catalyzing the decarboxylation of pyruvate to acetate and CO2 with quinone as an electron acceptor. Here, we investigate PQO activity in Corynebacterium glutamicum, examine purified PQO, and describe the crystal structure of the native enzyme and a truncated version. The specific PQO activity was highest in stationary phase cells grown in complex medium, lower in cells grown in complex medium containing glucose or acetate, and lowest in cells grown in minimal acetate-medium. A similar pattern with about 30-fold higher specific PQO activities was observed in C. glutamicum with plasmid-bound pqo expression under the control of the tac promoter, indicating that the differences in PQO activity are likely due to post-transcriptional control. Continuous cultivation of C. glutamicum at dilution rates between 0.05 and 0.4 h-1 revealed a negative correlation between PQO activity and growth rate. Kinetic analysis of PQO enzymes purified from cells grown in complex or in minimal acetate-medium revealed substantial differences in specific activity (72.3 vs. 11.9 U·mg protein-1) and turnover number (kcat: 440 vs. 78 s-1, respectively), suggesting post-translational modifications affecting PQO activity. Structural analysis of PQO revealed a homotetrameric arrangement very similar to the Escherichia coli pyruvate oxidase PoxB except for the C-terminal membrane binding domain, which exhibited a conformation markedly different from its PoxB counterpart. A truncated PQO variant lacking 17 C-terminal amino acids showed higher affinity to pyruvate and was independent of detergent activation, highlighting the importance of the C-terminus for enzyme activation and lipid binding.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857524","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}

引用次数: 0

Structures of BlEst2 from Bacillus licheniformis in its propeptide and mature forms reveal autoinhibitory effects of the C‐terminal domain 地衣芽孢杆菌 BlEst2 的前肽和成熟形式结构揭示了 C 端结构域的自动抑制作用

The FEBS journal Pub Date : 2024-07-27 DOI: 10.1111/febs.17229

Aline Minali Nakamura, Andre Schutzer Godoy, Marco Antônio Seiki Kadowaki, Lucas N. Trentin, Sinkler E. T. Gonzalez, Munir S. Skaf, Igor Polikarpov

{"title":"Structures of BlEst2 from Bacillus licheniformis in its propeptide and mature forms reveal autoinhibitory effects of the C‐terminal domain","authors":"Aline Minali Nakamura, Andre Schutzer Godoy, Marco Antônio Seiki Kadowaki, Lucas N. Trentin, Sinkler E. T. Gonzalez, Munir S. Skaf, Igor Polikarpov","doi":"10.1111/febs.17229","DOIUrl":"https://doi.org/10.1111/febs.17229","url":null,"abstract":"Carboxylesterases comprise a major class of α/β‐fold hydrolases responsible for the cleavage and formation of ester bonds. Found ubiquitously in nature, these enzymes are crucial for the metabolism of both endogenous and exogenous carboxyl esters in animals, plants and microorganisms. Beyond their essential physiological roles, carboxylesterases stand out as one of the important classes of biocatalysts for biotechnology. BlEst2, an enzyme previously classified as Bacillus licheniformis esterase, remains largely uncharacterized. In the present study, we elucidate the structural biology, molecular dynamics and biochemical features of BlEst2. Our findings reveal a canonical α/β‐hydrolase fold similar to the ESTHER block L of lipases, further augmented by two additional accessory C‐terminal domains. Notably, the catalytic domain demonstrates two insertions, which occupy conserved locations in α/β‐hydrolase proteins and commonly form the lid domain in lipase structures. Intriguingly, our in vitro cleavage of C‐terminal domains revealed the structure of the active form of BlEst2. Upon activation, BlEst2 showed a markedly elevated hydrolytic activity. This observation implies that the intramolecular C‐terminal domain serves as a regulatory intramolecular inhibitor. Interestingly, despite exhibiting esterase‐like activity, BlEst2 structural characteristics align more closely with lipases. This suggests that BlEst2 could potentially represent a previously unrecognized subgroup within the realm of carboxyl ester hydrolases.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141780272","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}

引用次数: 0

PACAP ameliorates obesity-induced insulin resistance through FAIM/Rictor/AKT axis PACAP通过FAIM/Rictor/AKT轴改善肥胖引起的胰岛素抵抗。

The FEBS journal Pub Date : 2024-07-23 DOI: 10.1111/febs.17228

Jia Feng, Wenhui Chen, Shanshan Li, Qianchen Fang, Xingwu Chen, Ge Bai, Meng Tian, Yongmei Huang, Pei Xu, Zixian Wang, Yi Ma

{"title":"PACAP ameliorates obesity-induced insulin resistance through FAIM/Rictor/AKT axis","authors":"Jia Feng, Wenhui Chen, Shanshan Li, Qianchen Fang, Xingwu Chen, Ge Bai, Meng Tian, Yongmei Huang, Pei Xu, Zixian Wang, Yi Ma","doi":"10.1111/febs.17228","DOIUrl":"10.1111/febs.17228","url":null,"abstract":"Obesity and obesity-related insulin resistance have been a research hotspot. Pituitary adenylate cyclase activating polypeptide (PACAP) has emerged as playing a significant role in energy metabolism, holding promising potential for attenuating insulin resistance. However, the precise mechanism is not fully understood. Palmitic acid and a high-fat diet (HFD) were used to establish insulin resistance model in Alpha mouse liver 12 cell line and C57BL/6 mice, respectively. Subsequently, we assessed the effects of PACAP both in vivo and in vitro. Lentivirus vectors were used to explore the signaling pathway through which PACAP may ameliorate insulin resistance. PACAP was found to selectively bind to the PACAP type I receptor receptor and ameliorate insulin resistance, which was characterized by increased glycogen synthesis and the suppression of gluconeogenesis in the insulin-resistant cell model and HFD-fed mice. These effects were linked to the activation of the Fas apoptotic inhibitory molecule/rapamycin-insensitive companion of mammalian target of rapamycin/RAC-alpha serine/threonine-protein kinase (FAIM/Rictor/AKT) axis. Furthermore, PACAP ameliorated insulin resistance by increasing solute carrier family 2, facilitated glucose transporter members 2/4 and inhibiting gluconeogenesis-related proteins glucose 6-phosphatase catalytic subunit 1 and phosphoenolpyruvate carboxykinase 2 expression. Meanwhile, the phosphorylation of hepatic AKT/glycogen synthase kinase 3β was promoted both in vivo and in vitro by PACAP. Additionally, PACAP treatment decreased body weight, food intake and blood glucose levels in obese mice. Our study shows that PACAP ameliorated insulin resistance through the FAIM/Rictor/AKT axis, presenting it as a promising drug candidate for the treatment of obesity-related insulin resistance.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750124","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}

引用次数: 0

AXIN2 promotes degradation of AXIN1 through tankyrase in colorectal cancer cells. AXIN2通过tankyrase促进结直肠癌细胞中AXIN1的降解。

The FEBS journal Pub Date : 2024-07-18 DOI: 10.1111/febs.17226

Olivia Schmidt, Martina Brückner, Dominic B Bernkopf

{"title":"AXIN2 promotes degradation of AXIN1 through tankyrase in colorectal cancer cells.","authors":"Olivia Schmidt, Martina Brückner, Dominic B Bernkopf","doi":"10.1111/febs.17226","DOIUrl":"https://doi.org/10.1111/febs.17226","url":null,"abstract":"AXIN1 and AXIN2 are homologous proteins that inhibit the Wnt/β-catenin signaling pathway, which is frequently hyperactive in colorectal cancer. Stabilization of AXIN1 and AXIN2 by inhibiting their degradation through tankyrase (TNKS) allows the attenuation of Wnt signaling in cancer, attracting interest for potential targeted therapy. Here, we found that knockout or knockdown of AXIN2 in colorectal cancer cells increased the protein stability of AXIN1. The increase in AXIN1 overcompensated for the loss of AXIN2 with respect to protein levels; however, functionally it did not because loss of AXIN2 activated the pathway. Moreover, AXIN2 was highly essential in the context of TNKS inhibition because TNKS-targeting small-molecule inhibitors completely failed to inhibit Wnt signaling and to stabilize AXIN1 in AXIN2 knockout cells. The increased AXIN1 protein stability and the impaired stabilization by TNKS inhibitors indicated disrupted TNKS-AXIN1 regulation in AXIN2 knockout cells. Concordantly, mechanistic studies revealed that co-expression of AXIN2 recruited TNKS to AXIN1 and stimulated TNKS-mediated degradation of transiently expressed AXIN1 wild-type and AXIN1 mutants with impaired TNKS binding. Taken together, our data suggest that AXIN2 promotes degradation of AXIN1 through TNKS in colorectal cancer cells by directly linking the two proteins, and these findings may be relevant for TNKS inhibition-based colorectal cancer therapies.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636268","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}

引用次数: 0

NFκB dynamics-dependent epigenetic changes modulate inflammatory gene expression and induce cellular senescence. 依赖于 NFκB 动态的表观遗传学变化可调节炎症基因表达并诱导细胞衰老。

The FEBS journal Pub Date : 2024-07-16 DOI: 10.1111/febs.17227

Sho Tabata, Keita Matsuda, Shou Soeda, Kenshiro Nagai, Yoshihiro Izumi, Masatomo Takahashi, Yasutaka Motomura, Ayaka Ichikawa Nagasato, Kazuyo Moro, Takeshi Bamba, Mariko Okada

{"title":"NFκB dynamics-dependent epigenetic changes modulate inflammatory gene expression and induce cellular senescence.","authors":"Sho Tabata, Keita Matsuda, Shou Soeda, Kenshiro Nagai, Yoshihiro Izumi, Masatomo Takahashi, Yasutaka Motomura, Ayaka Ichikawa Nagasato, Kazuyo Moro, Takeshi Bamba, Mariko Okada","doi":"10.1111/febs.17227","DOIUrl":"https://doi.org/10.1111/febs.17227","url":null,"abstract":"Upregulation of nuclear factor κB (NFκB) signaling is a hallmark of aging and a major cause of age-related chronic inflammation. However, its effect on cellular senescence remains unclear. Here, we show that alteration of NFκB nuclear dynamics from oscillatory to sustained by depleting a negative feedback regulator of NFκB pathway, NFκB inhibitor alpha (IκBα), in the presence of tumor necrosis factor α (TNFα) promotes cellular senescence. Sustained NFκB activity enhanced inflammatory gene expression through increased NFκB-DNA binding and slowed the cell cycle. IκBα protein was decreased under replicative or oxidative stress in vitro. Furthermore, a decrease in IκBα protein and an increase in DNA-NFκB binding at the transcription start sites of age-associated genes in aged mouse hearts suggested that nuclear NFκB dynamics may play a critical role in the progression of aging. Our study suggests that nuclear NFκB dynamics-dependent epigenetic changes regulated over time in a living system, possibly through a decrease in IκBα, enhance the expression of inflammatory genes to advance the cells to a senescent state.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141622082","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}

引用次数: 0