Cell ResearchPub Date : 2025-05-01Epub Date: 2025-03-20DOI: 10.1038/s41422-025-01090-y
Heng Zhang, Nana Cui, Xiong Ma, H Eric Xu
{"title":"Structural basis of augmenting taurine uptake by the taurine transporter in alleviating cellular senescence.","authors":"Heng Zhang, Nana Cui, Xiong Ma, H Eric Xu","doi":"10.1038/s41422-025-01090-y","DOIUrl":"10.1038/s41422-025-01090-y","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":"385-388"},"PeriodicalIF":28.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell ResearchPub Date : 2025-05-01DOI: 10.1038/s41422-024-01055-7
Pin Wang, Xiaoyu Hu
{"title":"Encoding immune responses: the moonlighting function of alanyl-tRNA synthetase.","authors":"Pin Wang, Xiaoyu Hu","doi":"10.1038/s41422-024-01055-7","DOIUrl":"10.1038/s41422-024-01055-7","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":"332-333"},"PeriodicalIF":28.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell ResearchPub Date : 2025-05-01DOI: 10.1038/s41422-025-01101-y
Liujia Qian, Zhen Dong, Tiannan Guo
{"title":"Grow AI virtual cells: three data pillars and closed-loop learning.","authors":"Liujia Qian, Zhen Dong, Tiannan Guo","doi":"10.1038/s41422-025-01101-y","DOIUrl":"10.1038/s41422-025-01101-y","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":"319-321"},"PeriodicalIF":28.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell ResearchPub Date : 2025-05-01Epub Date: 2025-04-03DOI: 10.1038/s41422-025-01107-6
Petr Broz
{"title":"Pyroptosis: molecular mechanisms and roles in disease.","authors":"Petr Broz","doi":"10.1038/s41422-025-01107-6","DOIUrl":"10.1038/s41422-025-01107-6","url":null,"abstract":"<p><p>Pyroptosis is a type of programmed necrosis triggered by the detection of pathogens or endogenous danger signals in the cytosol. Pyroptotic cells exhibit a swollen, enlarged morphology and ultimately undergo lysis, releasing their cytosolic contents - such as proteins, metabolites, and nucleic acids - into the extracellular space. These molecules can function as danger-associated molecular patterns (DAMPs), triggering inflammation when detected by neighboring cells. Mechanistically, pyroptosis is initiated by members of the gasdermin protein family, which were identified a decade ago as pore-forming executors of cell death. Mammalian gasdermins consist of a cytotoxic N-terminal domain, a flexible linker, and a C-terminal regulatory domain that binds to and inhibits the N-terminus. Proteolytic cleavage within the linker releases the N-terminal domain, enabling it to target various cellular membranes, including nuclear, mitochondrial, and plasma membranes, where it forms large transmembrane pores. Gasdermin pores in the plasma membrane disrupt the electrochemical gradient, leading to water influx and cell swelling. Their formation also activates the membrane protein ninjurin-1 (NINJ1), which oligomerizes to drive complete plasma membrane rupture and the release of large DAMPs. Since their discovery as pore-forming proteins, gasdermins have been linked to pyroptosis not only in host defense but also in various pathological conditions. This review explores the history of pyroptosis, recent insights into gasdermin activation, the cellular consequences of pore formation, and the physiological roles of pyroptosis.</p>","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":"334-344"},"PeriodicalIF":28.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell ResearchPub Date : 2025-05-01DOI: 10.1038/s41422-025-01105-8
Panyu Fei, Michael L Dustin
{"title":"Mechano-pharmacology of T cell receptor specificity.","authors":"Panyu Fei, Michael L Dustin","doi":"10.1038/s41422-025-01105-8","DOIUrl":"10.1038/s41422-025-01105-8","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":"324-325"},"PeriodicalIF":28.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell ResearchPub Date : 2025-05-01DOI: 10.1038/s41422-025-01102-x
Biyun Zhu, Shao Wei Hu, Yilai Shu
{"title":"Identification of a GPCR as a tip link-independent equilibrioceptor.","authors":"Biyun Zhu, Shao Wei Hu, Yilai Shu","doi":"10.1038/s41422-025-01102-x","DOIUrl":"10.1038/s41422-025-01102-x","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":"326-327"},"PeriodicalIF":28.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell ResearchPub Date : 2025-04-21DOI: 10.1038/s41422-025-01110-x
Xiaobo He, Qiu-Xia Wang, Denghui Wei, Yujie Lin, Xia Zhang, Yuanzhong Wu, Xuexia Qian, Zhihao Lin, Beibei Xiao, Qinxue Wu, Zhen Wang, Fengtao Zhou, Zhihao Wei, Jingxuan Wang, Run Gong, Ruhua Zhang, Qingling Zhang, Ke Ding, Song Gao, Tiebang Kang
{"title":"Lysosomal EGFR acts as a Rheb-GEF independent of its kinase activity to activate mTORC1","authors":"Xiaobo He, Qiu-Xia Wang, Denghui Wei, Yujie Lin, Xia Zhang, Yuanzhong Wu, Xuexia Qian, Zhihao Lin, Beibei Xiao, Qinxue Wu, Zhen Wang, Fengtao Zhou, Zhihao Wei, Jingxuan Wang, Run Gong, Ruhua Zhang, Qingling Zhang, Ke Ding, Song Gao, Tiebang Kang","doi":"10.1038/s41422-025-01110-x","DOIUrl":"https://doi.org/10.1038/s41422-025-01110-x","url":null,"abstract":"<p>Oncogenic mutations in EGFR often result in EGF-independent constitutive activation and aberrant trafficking and are associated with several human malignancies, including non-small cell lung cancer. A major consequence of EGFR mutations is the activation of the mechanistic target of rapamycin complex 1 (mTORC1), which requires EGFR kinase activity and downstream PI3K/AKT signaling, resulting in increased cell proliferation. However, recent studies have elucidated kinase-independent roles of EGFR in cell survival and cancer progression. Here, we report a <i>cis</i> mTORC1 activation function of EGFR that is independent of its kinase activity. Our results reveal that lysosomal localization of EGFR is critical to mTORC1 activation, where EGFR physically binds Rheb, acting as a guanine exchange factor (GEF) for Rheb, with its Glu804 serving as a potential glutamic finger. Genetic knock-in of EGFR-E804K in cells reduces the level of GTP-bound Rheb, and significantly suppresses mTORC1 activation, cell proliferation and tumor growth. Different tyrosine kinase inhibitors exhibit distinct effects on EGFR-induced mTORC1 activation, with afatinib, which additionally blocks EGFR’s GEF activity, causing a much greater suppression of mTORC1 activation and cell growth, and erlotinib, which targets only kinase activity, resulting in only a slight decrease. Moreover, a novel small molecule, BIEGi-1, was designed to target both the Rheb-GEF and kinase activities of EGFR, and shows a strong inhibitory effect on the viability of cells harboring EGFR mutants. These findings unveil a fundamental event in cell growth and suggest a promising strategy against cancers with EGFR mutations.</p>","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"47 1","pages":""},"PeriodicalIF":44.1,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell ResearchPub Date : 2025-04-21DOI: 10.1038/s41422-025-01120-9
Niklas A. Schmacke, Veit Hornung
{"title":"Decoding NLRP3: Phase separation enters the scene","authors":"Niklas A. Schmacke, Veit Hornung","doi":"10.1038/s41422-025-01120-9","DOIUrl":"https://doi.org/10.1038/s41422-025-01120-9","url":null,"abstract":"<p><b>Activation of the innate immune sensor protein NLRP3 leads to the assembly of a multiprotein complex called the inflammasome, causing cell death and inflammation. In a recent paper in</b> <b><i>Cell Research</i></b>, <b>Zou et al. now provide evidence that palmitoylation of NLRP3 promotes its liquid–liquid phase separation, driving inflammasome activation</b>.</p>","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"30 1","pages":""},"PeriodicalIF":44.1,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}