Protein & Cell最新文献

Tuning the Hsp70 chaperone cycle: emerging roles of GrpE-like NEFs in proteostasis and organelle function. 调节Hsp70伴侣周期：grpe样nef在蛋白质静止和细胞器功能中的新作用。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2025-10-24 DOI: 10.1093/procel/pwaf086

Marc A Morizono,Tiffany V Safar,Mark A Herzik

{"title":"Tuning the Hsp70 chaperone cycle: emerging roles of GrpE-like NEFs in proteostasis and organelle function.","authors":"Marc A Morizono,Tiffany V Safar,Mark A Herzik","doi":"10.1093/procel/pwaf086","DOIUrl":"https://doi.org/10.1093/procel/pwaf086","url":null,"abstract":"The heat shock protein 70 (Hsp70) family of molecular chaperones is essential for nearly every cell to support protein homeostasis through folding, signaling, and quality control. Hsp70 functionality critically depends on co-chaperones, including the GrpE-like family of nucleotide exchange factors (NEFs), first identified in Escherichia coli as GrpE. These factors have long been recognized for their ability to catalyze the release of Hsp70 nucleotide and protein substrates, but recent structural and functional studies have revealed that GrpE-like NEFs are more than passive exchange catalysts, instead acting as dynamic regulators that coordinate chaperone activity with cellular stress responses, organelle-specific demands, and allosteric control of substrate binding and release. In this review, we synthesize decades of research on GrpE-like proteins across bacteria and eukaryotes, culminating in high-resolution structures of the human mitochondrial NEF, GrpEL1, in complex with mitochondrial Hsp70. We examine how architectural features of GrpE-like NEFs have evolved to meet specialized demands, such as thermosensing in bacteria, redox-responsive regulation in vertebrates, and coordination of protein import in mitochondria. We further describe how discrete structural domains dynamically control chaperone cycling, including nucleotide and substrate release, and how gene duplication and domain specialization have driven functional diversification in higher eukaryotes. Finally, we highlight emerging evidence linking NEF activity to mitochondrial homeostasis, stress adaptation, and disease, reframing GrpE-like NEFs as tunable regulators rather than static cofactors. This perspective positions them as stress-adaptive control points in proteostasis and offers a conceptual framework for understanding how ancient chaperone systems have evolved to meet the regulatory needs of modern and complex eukaryotic cells.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":"1 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351655","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

Fibulin-7 in progenitor cells promotes adipose tissue fibrosis and disrupts metabolic homeostasis in obesity. 在肥胖中，祖细胞中的纤维蛋白-7促进脂肪组织纤维化并破坏代谢稳态。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2025-10-23 DOI: 10.1093/procel/pwaf084

Hairong Yu,Fan Yang,Dandan Yan,Wei Chen,Lijun Yao,Hongli Chen,Siyu Lai,Jinyin Zha,Yi Sun,Yicen Zong,Jian Yu,Hong Zhang,Feng Jiang,Rong Zhang,Jian Zhang,Jing Yan,Cheng Hu

{"title":"Fibulin-7 in progenitor cells promotes adipose tissue fibrosis and disrupts metabolic homeostasis in obesity.","authors":"Hairong Yu,Fan Yang,Dandan Yan,Wei Chen,Lijun Yao,Hongli Chen,Siyu Lai,Jinyin Zha,Yi Sun,Yicen Zong,Jian Yu,Hong Zhang,Feng Jiang,Rong Zhang,Jian Zhang,Jing Yan,Cheng Hu","doi":"10.1093/procel/pwaf084","DOIUrl":"https://doi.org/10.1093/procel/pwaf084","url":null,"abstract":"Fibrosis, resulting from excess extracellular matrix (ECM) deposition, is a feature of adipose tissue (AT) dysfunction and obesity-related insulin resistance. Emerging evidence indicates that adipogenic stem and precursor cells (ASPCs) are a crucial origin of ECM proteins and possess the potential to induce AT fibrosis. Here, we employed single-cell RNA-seq and identified a unique subset of ASPCs that closely associated with ECM function. Within this subset, we discerned a notable upregulation in the expression of Fibulin-7 (FBLN7), a secreted glycoprotein, in obese mice. Similarly, in humans, FBLN7 levels exhibited an increase in visceral fat among obese individuals and demonstrated a correlation with clinical metabolic traits. Functional studies further revealed that, in response to caloric excess, ASPCs-specific FBLN7 knockout mice display a diminished state of AT fibrosis-inflammation, along with improved systemic metabolic health. Notably, the depletion of FBLN7 in ASPCs suppressed TGF-β-induced fibrogenic responses, whereas its overexpression amplified such responses. Mechanistically, FBLN7 interacted with thrombospondin-1 (TSP1) via its EGF-like calcium-binding domain, thereby enhancing the stability of the TSP1 protein. This, in turn, facilitated the conversion of latent TGF-β to its bio-active form, subsequently promoting TGFBR1/Smad signaling pathways. Furthermore, we developed an anti-FBLN7 neutralizing antibody, which could dramatically alleviate diet-induced AT fibrosis. These results suggest that FBLN7, produced by ASPCs, exerts a major influence in the development of AT fibrosis and may represent a potential target for therapeutic intervention.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":"68 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339439","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

GABPA ensures proper blastocyst development by suppressing SMAD3-mediated TGF-β signaling. GABPA通过抑制smad3介导的TGF-β信号传导确保囊胚发育正常。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2025-10-23 DOI: 10.1093/procel/pwaf083

Junzhi Liao,Ying Ma,Yanjiang Liu,Rong Guo,Hongjie Yao

引用次数: 0

Engineering oncolytic bacteria as precision cancer therapeutics: design principles, therapeutic strategies, and translational perspectives. 作为精确癌症治疗的工程溶瘤细菌：设计原则、治疗策略和转化观点。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2025-10-23 DOI: 10.1093/procel/pwaf085

Lingxue Niu,Zhenqiang Deng,Yiyu Jin,Ningzi Guan,Haifeng Ye

{"title":"Engineering oncolytic bacteria as precision cancer therapeutics: design principles, therapeutic strategies, and translational perspectives.","authors":"Lingxue Niu,Zhenqiang Deng,Yiyu Jin,Ningzi Guan,Haifeng Ye","doi":"10.1093/procel/pwaf085","DOIUrl":"https://doi.org/10.1093/procel/pwaf085","url":null,"abstract":"Engineered oncolytic bacteria are emerging as a promising platform for precision cancer therapy, combining inherent tumor tropism, immunogenicity, and programmable gene control. Advances in synthetic biology now enable inducible and autonomous circuits that sense exogenous inputs (chemical signals or physical signals), bacterial self-cues (quorum sensing, bacterial invasion switches, or nitric oxide-responsive promoters), and tumor-specific pathophysiology (hypoxia, low pH, or lactate). These designs regulate colonization, lysis, and the spatiotemporally confined release of therapeutic cargos-including prodrug-converting enzymes, cytokines, and antibody/nanobody fragments-thereby enhancing antitumor efficacy while limiting off-target toxicity. Beyond monotherapy, oncolytic bacteria integrate with complementary modalities-including immune-checkpoint blockade, adoptive cell therapies (CAR-T/NK), radiotherapy/chemotherapy, nanomedicine, and oncolytic viruses-to amplify immune activation and to enable multimodal, synergistic regimens. Concurrently, biosensor modules transform bacterial chassis into programmable \"microbial factories\" that couple therapy with real-time imaging and adaptive responses within the tumor microenvironment. This review synthesizes design principles for bacterial gene regulation, surveys recent preclinical advances, and highlights emerging combination strategies, while outlining translational considerations for safety, manufacturability, and dosing, and patient selection. Together, these developments position engineered oncolytic bacteria as a promising route toward safe, effective, and ultimately personalized bacteria-based cancer therapeutics.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":"140 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339435","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

Pleural cavity macrophages promote lung tumor establishment through tissue invasion. 胸膜腔巨噬细胞通过组织侵袭促进肺肿瘤的形成。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2025-10-16 DOI: 10.1093/procel/pwaf078

Zhenqian Zhang,Hengwei Jin,Zhicong Liu,Mengyang Shi,Mingjun Zhang,Wenjuan Pu,Jie Li,Xuekun Li,Daqing Ma,Qiang Shu,Bin Zhou

引用次数: 0

Circadian rhythm disruption declines oocyte quality for fertility via PTEN/AKT pathway. 昼夜节律紊乱通过PTEN/AKT通路降低卵母细胞质量以促进生育。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2025-09-24 DOI: 10.1093/procel/pwaf080

Ping-Shuang Lu,Kun-Huan Zhang,Si-Le Wu,Rui-Jie Ma,Yuan-Jing Zou,Jia-Qian Ju,Hao-Lin Zhang,Yue Wang,Shao-Chen Sun

引用次数: 0

Deciphering the RNA Landscapes on Mammalian Cell Surfaces. 解读哺乳动物细胞表面的RNA景观。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2025-09-18 DOI: 10.1093/procel/pwaf079

Xiao Jiang,Chu Xu,Enzhuo Yang,Danhua Xu,Yong Peng,Xue Han,Jingwen Si,Qixin Shao,Zhuo Liu,Qiuxiao Chen,Weizhi He,Shuang He,Yanhui Xu,Chuan He,Xinxin Huang,Lulu Hu

{"title":"Deciphering the RNA Landscapes on Mammalian Cell Surfaces.","authors":"Xiao Jiang,Chu Xu,Enzhuo Yang,Danhua Xu,Yong Peng,Xue Han,Jingwen Si,Qixin Shao,Zhuo Liu,Qiuxiao Chen,Weizhi He,Shuang He,Yanhui Xu,Chuan He,Xinxin Huang,Lulu Hu","doi":"10.1093/procel/pwaf079","DOIUrl":"https://doi.org/10.1093/procel/pwaf079","url":null,"abstract":"Cell surface RNAs, notably glycoRNAs, have been reported, yet the precise compositions of surface RNAs across different primary cell types remain unclear. Here, we introduce a comprehensive suite of methodologies for profiling, imaging, and quantifying specific surface RNAs. We present AMOUR, a method leveraging T7-based linear amplification, to accurately profile surface RNAs while preserving plasma membrane integrity. By integrating fluorescently labeled DNA probes with live primary cells, and employing imaging along with flow cytometry analysis, we can effectively image and quantify representative surface RNAs. Utilizing these techniques, we have identified diverse non-coding RNAs present on mammalian cell surfaces, expanding beyond the known glycoRNAs. We confirm the membrane anchorage and quantify the abundance of several representative surface RNA molecules in cultured HeLa cells and human umbilical cord blood mononuclear cells (hUCB-MNCs). Our imaging and flow cytometry analyses unequivocally confirm the membrane localization of Y family RNAs, spliceosomal snRNA U5, mitochondrial rRNA MTRNR2, mitochondrial tRNA MT-TA, VTRNA1-1, and the long non-coding RNA XIST. Our study not only introduces effective approaches for investigating surface RNAs but also provides a detailed portrayal of the surface RNA landscapes of hUCB-MNCs and murine blood cells, paving the way for future research in the field of surface RNAs.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":"316 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089748","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

Correction to: MFSD12 affects glycosphingolipid metabolism by modulating lysosome homeostasis. 更正：MFSD12通过调节溶酶体稳态影响鞘糖脂代谢。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2025-09-09 DOI: 10.1093/procel/pwaf077

引用次数: 0

Oncogenic role of the SLC7A13-SLC3A1 cystine transporter in human luminal breast cancer and its cryo-EM structure. SLC7A13-SLC3A1胱氨酸转运体在人腔乳腺癌中的致癌作用及其低温电镜结构

IF 21.1 1区生物学

Protein & Cell Pub Date : 2025-09-08 DOI: 10.1093/procel/pwaf076

Jing Dong,Tianhao Shi,Bingbiao Lin,Xuetong Liu,Waner Wei,Zichi Geng,Mingcheng Liu,Renhong Yan,Jin-Tang Dong

{"title":"Oncogenic role of the SLC7A13-SLC3A1 cystine transporter in human luminal breast cancer and its cryo-EM structure.","authors":"Jing Dong,Tianhao Shi,Bingbiao Lin,Xuetong Liu,Waner Wei,Zichi Geng,Mingcheng Liu,Renhong Yan,Jin-Tang Dong","doi":"10.1093/procel/pwaf076","DOIUrl":"https://doi.org/10.1093/procel/pwaf076","url":null,"abstract":"Breast cancer is a prevalent malignancy worldwide. The majority of breast cancers belong to the estrogen receptor (ER)-positive luminal subtype that can be effectively treated with antiestrogen therapies. However, a significant portion of such malignancies become hormone-refractory and incurable. Cancer cells often uptake more cystines to increase glutathione (GSH) biosynthesis and reduce reactive oxygen species (ROS), thereby preventing ROS-induced ferroptosis and leading to therapeutic resistance. However, few molecules of these processes are targetable for cancer therapy. However, few therapeutic targets have been established that target these processes. Here, we report that the gene for SLC7A13, a member of the SLC7A13-SLC3A1 cystine transporter, was amplified and overexpressed in 19.7% and 49.7% of breast cancers, respectively. SLC7A13 amplification and overexpression were associated with worse overall survival and disease-free survival in patients with luminal breast cancer. Functionally, SLC7A13 overexpression promoted, while its silencing attenuated, cell survival or proliferation. Molecularly, SLC7A13 silencing reduced cystine uptake and GSH biosynthesis, leading to increased lipid ROS levels. The cryo-EM structure of the human SLC7A13-SLC3A1 complex was determined at 2.64 Å, revealing a dimer-of-heterodimers architecture similar to that of other SLC3A1-linked transporters. A specific substrate-binding pocket was identified, containing distinct residues, which suggests a regulatory role in the cystine transporter. These findings suggest that the SLC7A13-SLC3A1 cystine transporter is a therapeutic target for treating luminal breast cancer. They also provide the structural insights for therapeutic development targeting the cystine transporter.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":"30 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008740","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

A single-cell transcriptomic landscape characterizes the endocrine system aging in the mouse. 单细胞转录组的景观特征内分泌系统老化在小鼠。

IF 12.8 1区生物学

Protein & Cell Pub Date : 2025-09-01 DOI: 10.1093/procel/pwaf074

Ran Wei, Zhehao Du, Jue Wang, Jinlong Bi, Wencong Lyu, Haochen Wang, Jianuo He, Fanju Meng, Lijun Zhang, Chao Zhang, Chen Zhang, Wei Tao

{"title":"A single-cell transcriptomic landscape characterizes the endocrine system aging in the mouse.","authors":"Ran Wei, Zhehao Du, Jue Wang, Jinlong Bi, Wencong Lyu, Haochen Wang, Jianuo He, Fanju Meng, Lijun Zhang, Chao Zhang, Chen Zhang, Wei Tao","doi":"10.1093/procel/pwaf074","DOIUrl":"10.1093/procel/pwaf074","url":null,"abstract":"<p><p>The endocrine system is crucial for maintaining overall homeostasis. However, its cellular signatures have not been elucidated during aging. Here, we conducted the first-ever single-cell transcriptomic profiles from eight endocrine organs in young and aged mice, revealing the activation of cell-type-specific aging pathways, such as loss of proteostasis, genomic instability and reactive oxygen species (ROS). Among six sex-shared endocrine organs, aging severely impaired gene expression networks in functional endocrine cells, accompanied by enhanced immune infiltration and unfolded protein response (UPR). Mechanism investigations showed that expanded aging-associated exhausted T cells activated MHC-I-UPR axis across functional endocrine cells by releasing GZMK. The inhibition of GZMK receptors by small chemical molecules counteracted the UPR and senescence, suggesting the immune infiltration is a possible driver of endocrine aging. Machine learning identified CD59 as a novel aging feature in sex-shared functional endocrine cells. For two sex-specific endocrine organs, both aged ovaries and testes showed enhanced immune responses. Meanwhile, cell-type-specific aging-associated transcriptional changes revealed an enhanced ROS mainly in aged theca cells of ovaries, while aged spermatogonia in testes showed impaired DNA repair. This study provides a comprehensive analysis of endocrine system aging at single-cell resolution, offering profound insights into mechanisms of endocrine aging.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966365","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