Protein & Cell最新文献_第4页

Genome-wide investigation of transcription factor occupancy and dynamics using cFOOT-seq. 利用cFOOT-seq研究转录因子占用和动态。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2025-08-04 DOI: 10.1093/procel/pwaf071

Heng Wang,Ang Wu,Meng-Chen Yang,Di Zhou,Xiyang Chen,Zhifei Shi,Yiqun Zhang,Yu-Xin Liu,Kai Chen,Xiaosong Wang,Xiao-Fang Cheng,Baodan He,Yutao Fu,Lan Kang,Yujun Hou,Kun Chen,Shan Bian,Juan Tang,Jianhuang Xue,Chenfei Wang,Xiaoyu Liu,Jiejun Shi,Shaorong Gao,Jia-Min Zhang

{"title":"Genome-wide investigation of transcription factor occupancy and dynamics using cFOOT-seq.","authors":"Heng Wang,Ang Wu,Meng-Chen Yang,Di Zhou,Xiyang Chen,Zhifei Shi,Yiqun Zhang,Yu-Xin Liu,Kai Chen,Xiaosong Wang,Xiao-Fang Cheng,Baodan He,Yutao Fu,Lan Kang,Yujun Hou,Kun Chen,Shan Bian,Juan Tang,Jianhuang Xue,Chenfei Wang,Xiaoyu Liu,Jiejun Shi,Shaorong Gao,Jia-Min Zhang","doi":"10.1093/procel/pwaf071","DOIUrl":"https://doi.org/10.1093/procel/pwaf071","url":null,"abstract":"Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":"20 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825267","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}

引用次数: 0

Structural and mechanistic insights into symmetry conversion in plant GORK K+ channel regulation. 植物GORK - K+通道调节对称性转换的结构和机制研究。

IF 12.8 1区生物学

Protein & Cell Pub Date : 2025-08-03 DOI: 10.1093/procel/pwaf067

Qi-Yu Li, Li Qin, Ling-Hui Tang, Chun-Rui Zhang, Shouguang Huang, Ke Wang, Gao-Hua Zhang, Ning-Jie Hao, Qian Xiao, Tongxin Niu, Min Su, Rainer Hedrich, Yu-Hang Chen

{"title":"Structural and mechanistic insights into symmetry conversion in plant GORK K+ channel regulation.","authors":"Qi-Yu Li, Li Qin, Ling-Hui Tang, Chun-Rui Zhang, Shouguang Huang, Ke Wang, Gao-Hua Zhang, Ning-Jie Hao, Qian Xiao, Tongxin Niu, Min Su, Rainer Hedrich, Yu-Hang Chen","doi":"10.1093/procel/pwaf067","DOIUrl":"https://doi.org/10.1093/procel/pwaf067","url":null,"abstract":"GORK is a shaker-like potassium channel in plants that contains ankyrin (ANK) repeats. In guard cells, activation of GORK causes K+ efflux, reducing turgor pressure and closing stomata. However, how GORK is regulated remains largely elusive. Here, we solved the cryo-EM structure of Arabidopsis GORK, revealing an unusual symmetry reduction (from C4 to C2) feature within its tetrameric assembly. This symmetry reduction in GORK channel is driven by ANK dimerization, which disrupts the coupling between transmembrane helices and cytoplasmic domains, thus maintaining GORK in an autoinhibited state. Electrophysiological and structural analyses further confirmed that ANK dimerization inhibits GORK, and its removal restores C4 symmetry, converting GORK to an activatable state. This dynamic switching between C2 and C4 symmetry, mediated by ANK dimerization, presents a GORK target site that guard cells regulate to switch the plant K+ channel between inhibited and activatable states, thus controlling stomatal movement in response to environmental stimuli.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138556","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}

引用次数: 0

Systematic characterization of full-length RNA isoforms in human colorectal cancer at single-cell resolution. 人类结直肠癌单细胞分辨率下全长RNA亚型的系统表征。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2025-07-22 DOI: 10.1093/procel/pwaf049

Ping Lu,Yu Zhang,Yueli Cui,Yuhan Liao,Zhenyu Liu,Zhi-Jie Cao,Jun-E Liu,Lu Wen,Xin Zhou,Wei Fu,Fuchou Tang

{"title":"Systematic characterization of full-length RNA isoforms in human colorectal cancer at single-cell resolution.","authors":"Ping Lu,Yu Zhang,Yueli Cui,Yuhan Liao,Zhenyu Liu,Zhi-Jie Cao,Jun-E Liu,Lu Wen,Xin Zhou,Wei Fu,Fuchou Tang","doi":"10.1093/procel/pwaf049","DOIUrl":"https://doi.org/10.1093/procel/pwaf049","url":null,"abstract":"Dysregulated RNA splicing is a well-recognized characteristic of colorectal cancer (CRC); however, its intricacies remain obscure, partly due to challenges in profiling full-length transcript variants at single-cell level. Here, we employ high-depth long-read scRNA-seq to define the full-length transcriptome of colorectal epithelial cells in 12 CRC patients, revealing extensive isoform diversities and splicing alterations. Cancer cells exhibited increased transcript complexity, with widespread 3'-UTR shortening and reduced intron retention. Distinct splicing regulation patterns were observed between intrinsic-consensus molecular subtypes (iCMS), with iCMS3 displaying even higher splicing factor activities and more pronounced 3'-UTR shortening. Furthermore, we revealed substantial shifts in isoform usage that result in alterations of protein sequences from the same gene with distinct carcinogenic effects during tumorigenesis of CRC. Allele-specific expression analysis revealed dominant mutant allele expression in key oncogenes and tumor suppressors. Moreover, mutated PPIG was linked to widespread splicing dysregulation, and functional validation experiments confirmed its critical role in modulating RNA splicing and tumor-associated processes. Our findings highlight the transcriptomic plasticity in CRC and suggest novel candidate targets for splicing-based therapeutic strategies.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":"115 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693433","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}

引用次数: 0

Preparation of fatty acid solutions for investigating lipid signaling, metabolism, and lipid droplets. 制备脂肪酸溶液，用于研究脂质信号、新陈代谢和脂滴。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2025-07-19 DOI: 10.1093/procel/pwae068

Shuyan Zhang, Mengwei Zhang, Shimeng Xu, Xiaochuan Fu, Qiumin Liao, Bin Pan, Liujuan Cui, Pingsheng Liu

引用次数: 0

Amino acid metabolism in breast cancer: pathogenic drivers and therapeutic opportunities. 乳腺癌中的氨基酸代谢：致病因素和治疗机会。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2025-07-19 DOI: 10.1093/procel/pwaf011

Yawen Liu, Xiangyun Zong, Patricia Altea-Manzano, Jie Fu

{"title":"Amino acid metabolism in breast cancer: pathogenic drivers and therapeutic opportunities.","authors":"Yawen Liu, Xiangyun Zong, Patricia Altea-Manzano, Jie Fu","doi":"10.1093/procel/pwaf011","DOIUrl":"10.1093/procel/pwaf011","url":null,"abstract":"Amino acid metabolism plays a critical role in the progression and development of breast cancer. Cancer cells, including those in breast cancer, reprogram amino acid metabolism to meet the demands of rapid proliferation, survival, and immune evasion. This includes alterations in the uptake and utilization of amino acids, such as glutamine, serine, glycine, and arginine, which provide essential building blocks for biosynthesis, energy production, and redox homeostasis. Notably, the metabolic phenotypes of breast cancer cells vary across molecular subtypes and disease stages, emphasizing the need for patient stratification and personalized therapeutic strategies. Advances in multi-level diagnostics, including phenotyping and predictive tools, such as AI-based analysis and body fluid profiling, have highlighted the potential for tailoring treatments to individual metabolic profiles. Enzymes, such as glutaminase and serine hydroxymethyltransferase, often upregulated in breast cancer, represent promising therapeutic targets. Understanding the interplay between amino acid metabolism and breast cancer biology, alongside the integration of personalized medicine approaches, can uncover novel insights into tumor progression and guide the development of precision therapies. This review explores the metabolic pathways of amino acids in breast cancer, with a focus on their implications for personalized treatment strategies.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"506-531"},"PeriodicalIF":13.6,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459303","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}

引用次数: 0

Chromatin landscape alteration uncovers multiple transcriptional circuits during memory CD8+ T-cell differentiation. 染色质景观改变揭示了记忆 CD8+ T 细胞分化过程中的多个转录回路。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2025-07-19 DOI: 10.1093/procel/pwaf003

Qiao Liu, Wei Dong, Rong Liu, Luming Xu, Ling Ran, Ziying Xie, Shun Lei, Xingxing Su, Zhengliang Yue, Dan Xiong, Lisha Wang, Shuqiong Wen, Yan Zhang, Jianjun Hu, Chenxi Qin, Yongchang Chen, Bo Zhu, Xiangyu Chen, Xia Wu, Lifan Xu, Qizhao Huang, Yingjiao Cao, Lilin Ye, Zhonghui Tang

{"title":"Chromatin landscape alteration uncovers multiple transcriptional circuits during memory CD8+ T-cell differentiation.","authors":"Qiao Liu, Wei Dong, Rong Liu, Luming Xu, Ling Ran, Ziying Xie, Shun Lei, Xingxing Su, Zhengliang Yue, Dan Xiong, Lisha Wang, Shuqiong Wen, Yan Zhang, Jianjun Hu, Chenxi Qin, Yongchang Chen, Bo Zhu, Xiangyu Chen, Xia Wu, Lifan Xu, Qizhao Huang, Yingjiao Cao, Lilin Ye, Zhonghui Tang","doi":"10.1093/procel/pwaf003","DOIUrl":"10.1093/procel/pwaf003","url":null,"abstract":"Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"575-601"},"PeriodicalIF":13.6,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971978","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}

引用次数: 0

Dynamin 1-mediated endocytic recycling of glycosylated N-cadherin sustains the plastic mesenchymal state to promote ovarian cancer metastasis. 动力蛋白1介导的糖基化n -钙粘蛋白的内吞循环维持可塑间质状态，促进卵巢癌转移。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2025-07-19 DOI: 10.1093/procel/pwaf019

Yuee Cai, Zhangyan Guan, Yin Tong, Weiyang Zhao, Jiangwen Zhang, Ling Peng, Philip P C Ip, Sally K Y To, Alice S T Wong

引用次数: 0

A minimally invasive, fast on/off "odorgenetic" method to manipulate physiology. 一种微创、快速开/关的“气味生成”方法来操纵生理学。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2025-07-19 DOI: 10.1093/procel/pwae072

Yanqiong Wu, Xueqin Xu, Shanchun Su, Zeyong Yang, Xincai Hao, Wei Lu, Jianghong He, Juntao Hu, Xiaohui Li, Hong Yu, Xiuqin Yu, Yangqiao Xiao, Shuangshuang Lu, Linhan Wang, Wei Tian, Hongbing Xiang, Gang Cao, Wen Jun Tu, Changbin Ke

引用次数: 0

Correction to: ALKBH1 deficiency leads to loss of homeostasis in human diploid somatic cells. 更正：ALKBH1缺乏导致人类二倍体体细胞失去稳态。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2025-07-19 DOI: 10.1093/procel/pwaf008

引用次数: 0

BiFC and FACS-based CRISPR screening revealed that QKI promotes PABPN1 LLPS in colorectal cancer cells. bbic和基于facs的CRISPR筛选显示，QKI促进结直肠癌细胞中的PABPN1 LLPS。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2025-07-19 DOI: 10.1093/procel/pwaf022

Mengxia Li, Zhijie Hu, Yingye Huang, Yuting Han, Cheng Liang, Yuchi Liu, Runze Wu, Xin Lu, Ke Deng, Susu Liu, Xin Ou, Yuwei Li, Chao Liu, Xuening Li, Jingting Liang, Yonggui Fu, Anlong Xu

{"title":"BiFC and FACS-based CRISPR screening revealed that QKI promotes PABPN1 LLPS in colorectal cancer cells.","authors":"Mengxia Li, Zhijie Hu, Yingye Huang, Yuting Han, Cheng Liang, Yuchi Liu, Runze Wu, Xin Lu, Ke Deng, Susu Liu, Xin Ou, Yuwei Li, Chao Liu, Xuening Li, Jingting Liang, Yonggui Fu, Anlong Xu","doi":"10.1093/procel/pwaf022","DOIUrl":"10.1093/procel/pwaf022","url":null,"abstract":"Protein liquid-liquid phase separation (LLPS), a pivotal phenomenon intricately linked to cellular processes, is regulated by various other proteins. However, there is still a lack of high-throughput methods for screening protein regulators of LLPS in target proteins. Here, we developed a CRISPR/Cas9-based screening method to identify protein phase separation regulators by integrating bimolecular fluorescence complementation (BiFC) and fluorescence-activated cell sorting (FACS). Using this newly developed method, we screened the RNA-binding proteins that regulate PABPN1 phase separation and identified the tumor suppressor QKI as a promoter of PABPN1 phase separation. Furthermore, QKI exhibits decreased expression levels and diminished nuclear localization in colorectal cancer cells, resulting in reduced PABPN1 phase separation, which, in turn, promotes alternative polyadenylation (APA), cell proliferation, and migration in colorectal cancer.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"557-574"},"PeriodicalIF":13.6,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573701","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}

引用次数: 0