Journal of Molecular Cell Biology最新文献_第3页

Correction to: Mitochondrial aldehyde dehydrogenase rescues against diabetic cardiomyopathy through GSK3β-mediated preservation of mitochondrial integrity and Parkin-mediated mitophagy. 更正为线粒体醛脱氢酶通过 GSK3β 介导的线粒体完整性保护和 Parkin 介导的有丝分裂，拯救糖尿病心肌病。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-09-04 DOI: 10.1093/jmcb/mjae032

引用次数: 0

PHLDA2 is critical for p53-mediated ferroptosis and tumor suppression. PHLDA2 对 p53 介导的铁变态反应和肿瘤抑制至关重要。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-08-29 DOI: 10.1093/jmcb/mjae033

Xin Yang, Wei Gu

引用次数: 0

Discovery of Trametinib as an orchestrator for cytoskeletal vimentin remodeling. 发现 Trametinib 是细胞骨架波形蛋白重塑的协调者。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-08-26 DOI: 10.1093/jmcb/mjae009

Shuangshuang Zhao, Zhifang Li, Qian Zhang, Yue Zhang, Jiali Zhang, Gaofeng Fan, Xiaobao Cao, Yaming Jiu

{"title":"Discovery of Trametinib as an orchestrator for cytoskeletal vimentin remodeling.","authors":"Shuangshuang Zhao, Zhifang Li, Qian Zhang, Yue Zhang, Jiali Zhang, Gaofeng Fan, Xiaobao Cao, Yaming Jiu","doi":"10.1093/jmcb/mjae009","DOIUrl":"10.1093/jmcb/mjae009","url":null,"abstract":"The dynamic remodeling of the cytoskeletal network of vimentin intermediate filaments supports various cellular functions, including cell morphology, elasticity, migration, organelle localization, and resistance against mechanical or pathological stress. Currently available chemicals targeting vimentin predominantly induce network reorganization and shrinkage around the nucleus. Effective tools for long-term manipulation of vimentin network dispersion in living cells are still lacking, limiting in-depth studies on vimentin function and potential therapeutic applications. Here, we verified that a commercially available small molecule, trametinib, is capable of inducing spatial spreading of the cellular vimentin network without affecting its transcriptional or Translational regulation. Further evidence confirmed its low cytotoxicity and similar effects on different cell types. Importantly, Trametinib has no impact on the other two cytoskeletal systems, actin filaments and the microtubule network. Moreover, Trametinib regulates vimentin network dispersion rapidly and efficiently, with effects persisting for up to 48 h after drug withdrawal. We also ruled out the possibility that Trametinib directly affects the phosphorylation level of vimentin. In summary, we identified an unprecedented regulator Trametinib, which is capable of spreading the vimentin network toward the cell periphery, and thus complemented the existing repertoire of vimentin remodeling drugs in the field of cytoskeletal research.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of druggable host dependency factors shared by multiple SARS-CoV-2 variants of concern. 确定多种令人担忧的 SARS-CoV-2 变体所共有的药物对宿主的依赖性因素。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-08-26 DOI: 10.1093/jmcb/mjae004

Ilaria Frasson, Linda Diamante, Manuela Zangrossi, Elena Carbognin, Anna Dalla Pietà, Alessandro Penna, Antonio Rosato, Ranieri Verin, Filippo Torrigiani, Cristiano Salata, Marìa Paula Dizanzo, Lorenzo Vaccaro, Davide Cacchiarelli, Sara N Richter, Marco Montagner, Graziano Martello

{"title":"Identification of druggable host dependency factors shared by multiple SARS-CoV-2 variants of concern.","authors":"Ilaria Frasson, Linda Diamante, Manuela Zangrossi, Elena Carbognin, Anna Dalla Pietà, Alessandro Penna, Antonio Rosato, Ranieri Verin, Filippo Torrigiani, Cristiano Salata, Marìa Paula Dizanzo, Lorenzo Vaccaro, Davide Cacchiarelli, Sara N Richter, Marco Montagner, Graziano Martello","doi":"10.1093/jmcb/mjae004","DOIUrl":"10.1093/jmcb/mjae004","url":null,"abstract":"The high mutation rate of SARS-CoV-2 leads to the emergence of multiple variants, some of which are resistant to vaccines and drugs targeting viral elements. Targeting host dependency factors, e.g. cellular proteins required for viral replication, would help prevent the development of resistance. However, it remains unclear whether different SARS-CoV-2 variants induce conserved cellular responses and exploit the same core host factors. To this end, we compared three variants of concern and found that the host transcriptional response was conserved, differing only in kinetics and magnitude. Clustered regularly interspaced short palindromic repeats screening identified host genes required for each variant during infection. Most of the genes were shared by multiple variants. We validated our hits with small molecules and repurposed the US Food and Drug Administration-approved drugs. All the drugs were highly active against all the tested variants, including new variants that emerged during the study (Delta and Omicron). Mechanistically, we identified reactive oxygen species production as a key step in early viral replication. Antioxidants such as N-acetyl cysteine (NAC) were effective against all the variants in both human lung cells and a humanized mouse model. Our study supports the use of available antioxidant drugs, such as NAC, as a general and effective anti-COVID-19 approach.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139672024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolomic profiling reveals decreased serum cysteine levels during gestational diabetes mellitus progression. 代谢组学分析显示，血清半胱氨酸水平在妊娠糖尿病进展过程中有所下降。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-08-26 DOI: 10.1093/jmcb/mjae010

Mengyu Lai, Jiaomeng Li, Jiaying Yang, Qingli Zhang, Yujia Gong, Yuhang Ma, Fang Fang, Na Li, Yingxiang Zhai, Tingting Shen, Yongde Peng, Jia Liu, Yufan Wang

{"title":"Metabolomic profiling reveals decreased serum cysteine levels during gestational diabetes mellitus progression.","authors":"Mengyu Lai, Jiaomeng Li, Jiaying Yang, Qingli Zhang, Yujia Gong, Yuhang Ma, Fang Fang, Na Li, Yingxiang Zhai, Tingting Shen, Yongde Peng, Jia Liu, Yufan Wang","doi":"10.1093/jmcb/mjae010","DOIUrl":"10.1093/jmcb/mjae010","url":null,"abstract":"Gestational diabetes mellitus (GDM) is a pregnancy-related metabolic disorder associated with short-term and long-term adverse health outcomes, but its pathogenesis has not been clearly elucidated. Investigations of the dynamic changes in metabolomic markers in different trimesters may reveal the underlying pathophysiology of GDM progression. Therefore, in the present study, we analysed the metabolic profiles of 75 women with GDM and 75 women with normal glucose tolerance throughout the three trimesters. We found that the variation trends of 38 metabolites were significantly changed during GDM development. Specifically, longitudinal analyses revealed that cysteine (Cys) levels significantly decreased over the course of GDM progression. Further study showed that Cys alleviated GDM in female mice at gestational day 14.5, possibly by inhibiting phosphoenolpyruvate carboxykinase to suppress hepatic gluconeogenesis. Taken together, these findings suggest that the Cys metabolism pathway might play a crucial role in GDM and Cys supplementation represents a potential new treatment strategy for GDM patients.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comments on 'Adeno-to-squamous transition drives resistance to KRAS inhibition in LKB1 mutant lung cancer'. 关于 "LKB1突变型肺癌中腺癌向鳞癌转化驱动对KRAS抑制剂的耐药性 "的评论

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-08-26 DOI: 10.1093/jmcb/mjae013

Xinyuan Tong, Ningxia Zhang, Yun Xue, Hongbin Ji

引用次数: 0

Regulation of m6Am RNA modification and its implications in human diseases. m6Am RNA修饰的调控及其对人类疾病的影响。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-08-26 DOI: 10.1093/jmcb/mjae012

Hao Jin, Zhouyuanjing Shi, Tianhua Zhou, Shanshan Xie

{"title":"Regulation of m6Am RNA modification and its implications in human diseases.","authors":"Hao Jin, Zhouyuanjing Shi, Tianhua Zhou, Shanshan Xie","doi":"10.1093/jmcb/mjae012","DOIUrl":"10.1093/jmcb/mjae012","url":null,"abstract":"N 6,2'-O-dimethyladenosine (m6Am) is a prevalent modification frequently found at the 5' cap-adjacent adenosine of messenger RNAs (mRNAs) and small nuclear RNAs (snRNAs) and the internal adenosine of snRNAs. This dynamic and reversible modification is under the regulation of methyltransferases phosphorylated CTD interacting factor 1 and methyltransferase-like protein 4, along with the demethylase fat mass and obesity-associated protein. m6Am RNA modification plays a crucial role in the regulation of pre-mRNA splicing, mRNA stability, and translation, thereby influencing gene expression. In recent years, there has been growing interest in exploring the functions of m6Am and its relevance to human diseases. In this review, we provide a comprehensive overview of the current knowledge concerning m6Am, with a focus on m6Am-modifying enzymes, sequencing approaches for its detection, and its impacts on pre-mRNA splicing, mRNA stability, and translation regulation. Furthermore, we highlight the roles of m6Am in the context of obesity, viral infections, and cancers, unravelling its underlying regulatory mechanisms.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11345611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Telomeric DNA breaks in human induced pluripotent stem cells trigger ATR-mediated arrest and telomerase-independent telomere damage repair. 人类诱导多能干细胞中的端粒DNA断裂触发ATR介导的阻滞和端粒酶非依赖性的端粒损伤修复。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-08-26 DOI: 10.1093/jmcb/mjad058

Katrina N Estep, John W Tobias, Rafael J Fernandez, Brinley M Beveridge, F Brad Johnson

{"title":"Telomeric DNA breaks in human induced pluripotent stem cells trigger ATR-mediated arrest and telomerase-independent telomere damage repair.","authors":"Katrina N Estep, John W Tobias, Rafael J Fernandez, Brinley M Beveridge, F Brad Johnson","doi":"10.1093/jmcb/mjad058","DOIUrl":"10.1093/jmcb/mjad058","url":null,"abstract":"Although mechanisms of telomere protection are well-defined in differentiated cells, how stem cells sense and respond to telomere dysfunction, in particular telomeric double-strand breaks (DSBs), is poorly characterized. Here, we report the DNA damage signaling, cell cycle, and transcriptome changes in human induced pluripotent stem cells (iPSCs) in response to telomere-internal DSBs. We engineer human iPSCs with an inducible TRF1-FokI fusion protein to acutely induce DSBs at telomeres. Using this model, we demonstrate that TRF1-FokI DSBs activate an ATR-dependent DNA damage response, which leads to p53-independent cell cycle arrest in G2. Using CRISPR-Cas9 to cripple the catalytic domain of telomerase reverse transcriptase, we show that telomerase is largely dispensable for survival and lengthening of TRF1-FokI-cleaved telomeres, which instead are effectively repaired by robust homologous recombination (HR). In contrast to HR-based telomere maintenance in mouse embryonic stem cells, where HR causes ZSCAN4-dependent extension of telomeres beyond their initial lengths, HR-based repair of telomeric breaks is sufficient to maintain iPSC telomeres at a normal length, which is compatible with sustained survival of the cells over several days of TRF1-FokI induction. Our findings suggest a previously unappreciated role for HR in telomere maintenance in telomerase-positive iPSCs and reveal distinct iPSC-specific responses to targeted telomeric DNA damage.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11429528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41099295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A polarized multicomponent foundation upholds ciliary central microtubules. 纤毛中心微管由极化的多成分基础支撑。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-08-20 DOI: 10.1093/jmcb/mjae031

Qingxia Chen, Huijie Zhao, Xinwen Pan, Chuyu Fang, Benhua Qiu, Jingting Guo, Xiumin Yan, Xueliang Zhu

{"title":"A polarized multicomponent foundation upholds ciliary central microtubules.","authors":"Qingxia Chen, Huijie Zhao, Xinwen Pan, Chuyu Fang, Benhua Qiu, Jingting Guo, Xiumin Yan, Xueliang Zhu","doi":"10.1093/jmcb/mjae031","DOIUrl":"https://doi.org/10.1093/jmcb/mjae031","url":null,"abstract":"Cilia's back-and-forth beat pattern requires a central pair (CP) of microtubules. However, the mechanism by which the CP is upheld above the transition zone (TZ) remains unclear. Here, we showed that a rod-like substructure marked by Cep131 and ciliary Centrin serves as a polarized CP-supporting foundation. This CP-foundation (CPF) was assembled independently of the CP during ciliogenesis in mouse ependymal cells. It protruded from the distal end of the basal body out of the TZ to enwrap the proximal end of the CP. Through proximity labeling, we identified 26 potential CPF components, among which Ccdc148 specifically localized at the proximal region of Centrin-decorated CPF and was complementary to the Cep131-enriched distal region. Cep131 deficiency abolished the CPF, resulting in CP penetration into the TZ. Consequently, cilia became prone to ultrastructural abnormality and paralysis, and Cep131-deficient mice were susceptible to late-onset hydrocephalus. In addition to Centrin, phylogenetic analysis also indicated conservations of Ccdc131 and Ccdc148 from protists to mammals, suggesting that the CPF is an evolutionarily conserved multicomponent CP-supporting platform in cilia.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142010230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Modeling gastric intestinal metaplasia in 3D organoids using nitrosoguanidine. 利用亚硝基胍在三维有机体中模拟胃肠化生。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-08-17 DOI: 10.1093/jmcb/mjae030

Yuan Li, Jiena Chen, Tao Li, Jie Lin, Haocheng Zheng, Nadia Johnson, Xuebiao Yao, Xia Ding

{"title":"Modeling gastric intestinal metaplasia in 3D organoids using nitrosoguanidine.","authors":"Yuan Li, Jiena Chen, Tao Li, Jie Lin, Haocheng Zheng, Nadia Johnson, Xuebiao Yao, Xia Ding","doi":"10.1093/jmcb/mjae030","DOIUrl":"https://doi.org/10.1093/jmcb/mjae030","url":null,"abstract":"Gastric intestinal metaplasia (GIM) represents a precancerous stage characterized by morphological and pathophysiological changes in the gastric mucosa, where gastric epithelial cells transform into a phenotype resembling that of intestinal cells. Previous studies have demonstrated that the intragastric administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induces both gastric carcinoma and intestinal metaplasia in mice. Here, we show that MNNG induces GIM in three-dimensional (3D) mouse organoids. Our histological analyses reveal that MNNG-induced gastric organoids undergo classical morphological alterations, exhibiting a distinct up-regulation of CDX2 and MUC2, along with a down-regulation of ATP4B and MUC6. Importantly, metaplastic cells observed in MNNG-treated organoids originate from MIST1+ cells, indicating their gastric chief cell lineage. Functional analyses show that activation of the RAS signaling pathway drives MNNG-induced metaplasia in 3D organoids, mirroring the characteristics observed in human GIM. Consequently, modeling intestinal metaplasia using 3D organoids offers valuable insights into the molecular mechanisms and spatiotemporal dynamics of the gastric epithelial lineage during the development of intestinal metaplasia within the gastric mucosa. We conclude that the MNNG-induced metaplasia model utilizing 3D organoids provides a robust platform for developing preventive and therapeutic strategies to mitigate the risk of gastric cancer before precancerous lesions occur.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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