Cell insight最新文献

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IF 6.4

Cell insight Pub Date : 2026-10-01 Epub Date: 2026-09-30 DOI: 10.1016/S2772-8927(26)00073-8

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IF 6.4

Cell insight Pub Date : 2026-08-01 Epub Date: 2026-07-23 DOI: 10.1016/S2772-8927(26)00049-0

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Cell insight Pub Date : 2026-06-01 Epub Date: 2026-06-03 DOI: 10.1016/S2772-8927(26)00036-2

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Cell insight Pub Date : 2026-04-01 Epub Date: 2026-04-06 DOI: 10.1016/S2772-8927(26)00018-0

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Structural and mechanistic basis of ADAR1-mediated RNA editing and immune regulation adar1介导的RNA编辑和免疫调节的结构和机制基础

Cell insight Pub Date : 2026-04-01 Epub Date: 2026-01-24 DOI: 10.1016/j.cellin.2026.100299

Xiangyu Deng , Mariam Elsharkawy , Yang Gao

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Fight Alzheimer's disease with cancer 用癌症对抗阿尔茨海默病

Cell insight Pub Date : 2026-04-01 Epub Date: 2026-01-24 DOI: 10.1016/j.cellin.2026.100300

Tongmei Zhang , Weihong Song

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Phosphorylation of FBXL3 mediates GLDC polyubiquitination to suppress MHC-I expression and promote cancer immune evasion FBXL3磷酸化介导GLDC多泛素化，抑制MHC-I表达，促进癌症免疫逃逸

Cell insight Pub Date : 2026-04-01 Epub Date: 2026-02-03 DOI: 10.1016/j.cellin.2026.100308

Rui Liu, Shu Li

{"title":"Phosphorylation of FBXL3 mediates GLDC polyubiquitination to suppress MHC-I expression and promote cancer immune evasion","authors":"Rui Liu, Shu Li","doi":"10.1016/j.cellin.2026.100308","DOIUrl":"10.1016/j.cellin.2026.100308","url":null,"abstract":"<div><div>Glycine decarboxylase (GLDC) is overexpressed in multiple tumor types and contributes to tumorigenesis or immune evasion by unclarified mechanisms. Here we report that GLDC is polyubiquitinated at K636 following EGFR activation, which drives GLDC-dependent transcriptional inhibition of MHC-I genes and induces tumor cells to evade CD8<sup>+</sup> T cell-mediated immunosurveillance. Mechanistically, EGFR activation triggers SRC-mediated FBXL3 phosphorylation at Y306, enabling its interaction with GLDC in nucleus. FBXL3 targets GLDC<sup>K636</sup> for K63-linked polyubiquitination, and promotes the interaction of GLDC with SMARCE1/DMAP1 to inhibit STAT1-triggered transcriptional activation, resulting in transcriptional inhibition of downstream MHC-I genes. Phosphorylation of FBXL3<sup>Y306</sup> decreases MHC-I levels in tumor cells and inhibits CD8<sup>+</sup> T cells immunity in tumors. Consistently, inhibitors of SRC improves tumor-specific CD8<sup>+</sup> T cells functions in TME and sensitizes antitumor effects of anti-PD-1 therapy. Our findings reveal an SRC-FBXL3-GLDC-MHC-I regulatory circuit that underlies CD8<sup>+</sup> T cells immune evasion, and provide a potential therapeutic target to enhance ICB therapy.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"5 2","pages":"Article 100308"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192148","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}

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Tuning the state: Matching condensate material properties with physiological demands and pathological dysfunction 调节状态：使凝析物质的特性与生理需求和病理功能障碍相匹配

Cell insight Pub Date : 2026-04-01 Epub Date: 2026-02-04 DOI: 10.1016/j.cellin.2026.100309

Jingxuan Luo , Zhehao Li , Ziyin Shen , Xiaoyu Zhai , Jiayue Chen , Hanchun Wang , Xueping Zhao , Jing He , Mingrui Ding

{"title":"Tuning the state: Matching condensate material properties with physiological demands and pathological dysfunction","authors":"Jingxuan Luo , Zhehao Li , Ziyin Shen , Xiaoyu Zhai , Jiayue Chen , Hanchun Wang , Xueping Zhao , Jing He , Mingrui Ding","doi":"10.1016/j.cellin.2026.100309","DOIUrl":"10.1016/j.cellin.2026.100309","url":null,"abstract":"<div><div>Biomolecular condensates have emerged as fundamental organizers of cellular biochemistry. Increasing evidence indicates that cellular condensates exhibit a broad spectrum of material properties—including viscoelastic, soft glass-like, gel-like, and quasi-solid regimes—that are intimately coupled to indicated diverse demands.</div><div>Here, we advance a material property-based framework for condensate biology, arguing that condensate material states are not incidental byproducts of molecular crowding or pathology, but are actively tuned to meet specific biological demands. Drawing on representative examples from Xist-mediated chromosome inactivation, chromatin organization, and postsynaptic density assembly, we illustrate how distinct material properties encode functional constraints such as spatial persistence, mechanical stability, and regulated molecular exchange.</div><div>We further discuss the molecular and structural principles underlying these material states, emphasizing the roles of interaction network architecture, multivalency, and internal patterning. We review emerging experimental approaches for probing condensate material properties <em>in vivo</em>, highlighting both their strengths and limitations. In particular, we position cryo–electron tomography as a structural tool for visualizing near-native internal organization and network connectivity, which constrains—but does not by itself define—condensate material behavior, and must be integrated with dynamic and mechanical measurements.</div><div>Together, this review reframes biomolecular condensates as functionally selected materials and provides a conceptual foundation for understanding how molecular organization gives rise to emergent material properties in physiology and pathology.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"5 2","pages":"Article 100309"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192147","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

An additional site mutation in MITA/STING gain-of-function mutants abolishes the autoimmune SAVI phenotypes and directs a therapeutic strategy MITA/STING功能获得突变体中的另一个位点突变可消除自身免疫性SAVI表型并指导治疗策略

Cell insight Pub Date : 2026-02-01 Epub Date: 2026-01-07 DOI: 10.1016/j.cellin.2026.100298

Fang-Xu Li , Sheng Liu , Zhi-Dong Zhang , Xin Shuai , Bi-Kun Xiao , Jia Yang , Defen Lu , Dandan Lin , Guijun Shang , Bo Zhong

{"title":"An additional site mutation in MITA/STING gain-of-function mutants abolishes the autoimmune SAVI phenotypes and directs a therapeutic strategy","authors":"Fang-Xu Li , Sheng Liu , Zhi-Dong Zhang , Xin Shuai , Bi-Kun Xiao , Jia Yang , Defen Lu , Dandan Lin , Guijun Shang , Bo Zhong","doi":"10.1016/j.cellin.2026.100298","DOIUrl":"10.1016/j.cellin.2026.100298","url":null,"abstract":"<div><div>STING-associated vasculopathy with onset in infancy (SAVI) is an autoimmune disease caused by gain-of-function mutations (GOFs) of MITA/STING and the most frequent GOFs for SAVI are MITA<sup>N154S</sup> and MITA<sup>V155M</sup>. However, how MITA GOFs are spontaneously activated remains incompletely understood. Here, we show that the activity of MITA hinge-region GOFs is compromised by an additional mutation at Lys150 and that the SAVI phenotypes of MITA<sup>N153S/WT</sup> mice are completely abolished in the MITA<sup>K150N/N153S</sup> (MITA<sup>NS/NS</sup>) mice. Mechanistically, MITA GOFs constitutively associate with iRhom2 for the spontaneous ER-to-Golgi translocation, which is substantially inhibited by the introduction of a mutation at Lys150. Interestingly, cGAMP binds to MITA<sup>NS</sup>, triggers the ER-to-Golgi translocation of MITA<sup>NS</sup> as well as the MITA<sup>NS</sup>-iRhom2 interaction, and induces the expression of downstream genes in <em>Mita</em><sup>NS/NS</sup> cells similarly as in <em>Mita</em><sup>+/+</sup> cells. Consistently, structural studies demonstrate an inactive open conformation of apo-MITA<sup>NS</sup> characterized by connector region crossover and a curved filament of cGAMP-bound MITA<sup>NS</sup> characterized by parallel connector regions, similar to those observed in wild-type MITA. Furthermore, we design a SAVI-inhibitory peptide (SIP) that selectively inhibits the interaction between hMITA<sup>N154S</sup> (mMITA<sup>N153S</sup>) and iRhom2 and the activity of MITA GOFs and thereby abolishes the SAVI phenotypes of the MITA<sup>N153S/WT</sup>→WT chimeric mice. These findings reveal a previously uncharacterized mechanism for the spontaneous activation of MITA GOFs and highlight a potential therapeutic intervention for SAVI.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"5 1","pages":"Article 100298"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037087","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

CXCL4 and CXCL4L1 activate human macrophage via TLR4 signaling to modulate inflammatory responses CXCL4和CXCL4L1通过TLR4信号激活人巨噬细胞，调节炎症反应

Cell insight Pub Date : 2026-02-01 Epub Date: 2025-11-06 DOI: 10.1016/j.cellin.2025.100287

Han Bai , Ruoxi Yuan , Dong Yan , Liyuan Liang , Ru Zhang , Yao Xu , Zeqiong Cai , Doudou Ren , Yueyang Chong , Kexin Wang , Rongfu Tu , Miao Li , Xiao Zhao , Yanan Wang , Yurong Chen , Ying Cui , Yaguang Zhang , Chao Yang

{"title":"CXCL4 and CXCL4L1 activate human macrophage via TLR4 signaling to modulate inflammatory responses","authors":"Han Bai , Ruoxi Yuan , Dong Yan , Liyuan Liang , Ru Zhang , Yao Xu , Zeqiong Cai , Doudou Ren , Yueyang Chong , Kexin Wang , Rongfu Tu , Miao Li , Xiao Zhao , Yanan Wang , Yurong Chen , Ying Cui , Yaguang Zhang , Chao Yang","doi":"10.1016/j.cellin.2025.100287","DOIUrl":"10.1016/j.cellin.2025.100287","url":null,"abstract":"<div><div>The chemokine CXCL4 activates human monocytes/macrophages and contributes to the pathogenesis of inflammatory and fibrotic diseases. However, the receptor of CXCL4, CXCR3, is not expressed in human monocytes/macrophages. Thus, signaling pathways and receptors that mediate human monocytes/macrophages response to CXCL4 alone are not well characterized. Using human primary monocytes and mouse bone marrow-derived macrophages, we reported that CXCL4 activated NF-κB and a TBK1-JNK-AP1 signaling axis that drove the expression of inflammatory, fibrotic and neutrophil chemokine genes, and also a TRIF-RIPK3 axis-dependent necroptosis in primary human monocytes. Surprisingly, multiple evidence targeting TLR4 expression and function suggested a role for TLR4 in CXCL4 responses. Further, we show that CXCL4 and its natural variant CXCL4L1 interact with TLR4/MD-2 complex in human monocytes and CXCL4L1 induced a transcriptomic profile divergent to LPS. Ectopic expression of human CXCL4L1 using adeno-associated virus (AAV) system effectively mitigated papain-induced asthma in wild-type (WT) mice. Notably, the therapeutic impact of CXCL4L1 was absent in <em>Tlr4</em><sup>−/−</sup> mice. Our findings indicate that CXCL4 and its variant CXCL4L1 modulate inflammatory and fibrotic gene expression, as well as necroptosis in human monocytes, and regulating lung inflammation through TLR4-dependent signaling, highlighting TLR4's critical role in the pathophysiological response to CXCL4/CXCL4L1.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"5 1","pages":"Article 100287"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145665347","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