Protein & Cell最新文献

ER membrane remodeling by targeting RTN4 induces pyroptosis to facilitate antitumor immune. 通过靶向 RTN4 重塑 ER 膜，诱导热蛋白沉积，促进抗肿瘤免疫。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2024-09-10 DOI: 10.1093/procel/pwae049

Mei-Mei Zhao,Ting-Ting Ren,Jing-Kang Wang,Lu Yao,Ting-Ting Liu,Ji-Chao Zhang,Yang Liu,Lan Yuan,Dan Liu,Jiu-Hui Xu,Peng-Fei Tu,Xiao-Dong Tang,Ke-Wu Zeng

{"title":"ER membrane remodeling by targeting RTN4 induces pyroptosis to facilitate antitumor immune.","authors":"Mei-Mei Zhao,Ting-Ting Ren,Jing-Kang Wang,Lu Yao,Ting-Ting Liu,Ji-Chao Zhang,Yang Liu,Lan Yuan,Dan Liu,Jiu-Hui Xu,Peng-Fei Tu,Xiao-Dong Tang,Ke-Wu Zeng","doi":"10.1093/procel/pwae049","DOIUrl":"https://doi.org/10.1093/procel/pwae049","url":null,"abstract":"Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the \"bubble\" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to PKM2-dependent conventional caspase-3/GSDME cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-PD-1. In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":null,"pages":null},"PeriodicalIF":21.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165961","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

RADICAL: a rationally designed ion channel activated by ligand for chemogenetics. RADICAL：通过配体激活的合理设计的离子通道，用于化学遗传学。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2024-09-03 DOI: 10.1093/procel/pwae048

Heng Zhang, Zhiwei Zheng, Xiaoying Chen, Lizhen Xu, Chen Guo, Jiawei Wang, Yihui Cui, Fan Yang

引用次数: 0

Dietary pyruvate targets cytosolic phospholipase A2 to mitigate inflammation and obesity in mice. 膳食丙酮酸以细胞膜磷脂酶 A2 为靶标，减轻小鼠的炎症和肥胖。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2024-09-01 DOI: 10.1093/procel/pwae014

Sadaf Hasan, Nabil Ghani, Xiangli Zhao, Julia Good, Amanda Huang, Hailey Lynn Wrona, Jody Liu, Chuan-Ju Liu

{"title":"Dietary pyruvate targets cytosolic phospholipase A2 to mitigate inflammation and obesity in mice.","authors":"Sadaf Hasan, Nabil Ghani, Xiangli Zhao, Julia Good, Amanda Huang, Hailey Lynn Wrona, Jody Liu, Chuan-Ju Liu","doi":"10.1093/procel/pwae014","DOIUrl":"10.1093/procel/pwae014","url":null,"abstract":"Obesity has a multifactorial etiology and is known to be a state of chronic low-grade inflammation, known as meta-inflammation. This state is associated with the development of metabolic disorders such as glucose intolerance and nonalcoholic fatty liver disease. Pyruvate is a glycolytic metabolite and a crucial node in various metabolic pathways. However, its role and molecular mechanism in obesity and associated complications are obscure. In this study, we reported that pyruvate substantially inhibited adipogenic differentiation in vitro and its administration significantly prevented HFD-induced weight gain, white adipose tissue inflammation, and metabolic dysregulation. To identify the target proteins of pyruvate, drug affinity responsive target stability was employed with proteomics, cellular thermal shift assay, and isothermal drug response to detect the interactions between pyruvate and its molecular targets. Consequently, we identified cytosolic phospholipase A2 (cPLA2) as a novel molecular target of pyruvate and demonstrated that pyruvate restrained diet-induced obesity, white adipose tissue inflammation, and hepatic steatosis in a cPLA2-dependent manner. Studies with global ablation of cPLA2 in mice showed that the protective effects of pyruvate were largely abrogated, confirming the importance of pyruvate/cPLA2 interaction in pyruvate attenuation of inflammation and obesity. Overall, our study not only establishes pyruvate as an antagonist of cPLA2 signaling and a potential therapeutic option for obesity but it also sheds light on the mechanism of its action. Pyruvate's prior clinical use indicates that it can be considered a safe and viable alternative for obesity, whether consumed as a dietary supplement or as part of a regular diet.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11365557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140185370","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

The expanded application of CAR-T cell therapy for the treatment of multiple non-tumoral diseases. 扩大 CAR-T 细胞疗法在治疗多种非肿瘤性疾病方面的应用。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2024-09-01 DOI: 10.1093/procel/pwad061

Zhuoqun Liu, Yuchen Xiao, Jianjun Lyu, Duohui Jing, Liu Liu, Yanbin Fu, Wenxin Niu, Lingjing Jin, Chao Zhang

引用次数: 0

Proteomic analysis of ferroptosis pathways reveals a role of CEPT1 in suppressing ferroptosis. 铁蛋白沉积途径的蛋白质组分析揭示了 CEPT1 在抑制铁蛋白沉积中的作用。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2024-09-01 DOI: 10.1093/procel/pwae004

Xiaoguang Liu, Zhen Chen, Yuelong Yan, Fereshteh Zandkarimi, Litong Nie, Qidong Li, Amber Horbath, Kellen Olszewski, Lavanya Kondiparthi, Chao Mao, Hyemin Lee, Li Zhuang, Masha Poyurovsky, Brent R Stockwell, Junjie Chen, Boyi Gan

引用次数: 0

Metabolic cell death in cancer: ferroptosis, cuproptosis, disulfidptosis, and beyond. 癌症中的代谢性细胞死亡：铁蜕变、杯蜕变、二硫化碳蜕变及其他。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2024-09-01 DOI: 10.1093/procel/pwae003

Chao Mao, Min Wang, Li Zhuang, Boyi Gan

引用次数: 0

Lcn2 secreted by macrophages through NLRP3 signaling pathway induced severe pneumonia. 巨噬细胞通过 NLRP3 信号通路分泌的 Lcn2 可诱发重症肺炎。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2024-08-24 DOI: 10.1093/procel/pwae045

Mingya Liu, Feifei Qi, Jue Wang, Fengdi Li, Qi Lv, Ran Deng, Xujian Liang, Shasha Zhou, Pin Yu, Yanfeng Xu, Yaqing Zhang, Yiwei Yan, Ming Liu, Shuyue Li, Guocui Mou, Linlin Bao

引用次数: 0

Molecular architecture of mammalian pyruvate dehydrogenase complex. 哺乳动物丙酮酸脱氢酶复合物的分子结构。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2024-08-24 DOI: 10.1093/procel/pwae044

Maofei Chen, Yutong Song, Sensen Zhang, Yitang Zhang, Xudong Chen, Minghui Zhang, Meng Han, Xin Gao, Sai Li, Maojun Yang

引用次数: 0

Adenosine-to-Inosine RNA editing in cancer: molecular mechanisms and downstream targets. 癌症中的腺苷转肌苷 RNA 编辑：分子机制和下游靶点。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2024-08-10 DOI: 10.1093/procel/pwae039

Hao Cheng, Jun Yu, Chi Chun Wong

引用次数: 0

Advances in Gene and Cellular Therapeutic Approaches for Huntington's Disease. 亨廷顿氏症基因和细胞治疗方法的进展。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2024-08-09 DOI: 10.1093/procel/pwae042

Xuejiao Piao, Dan Li, Hui Liu, Qing Guo, Yang Yu

{"title":"Advances in Gene and Cellular Therapeutic Approaches for Huntington's Disease.","authors":"Xuejiao Piao, Dan Li, Hui Liu, Qing Guo, Yang Yu","doi":"10.1093/procel/pwae042","DOIUrl":"https://doi.org/10.1093/procel/pwae042","url":null,"abstract":"Huntington's disease (HD) is an inherited neurodegenerative disorder caused by the abnormal expansion of CAG trinucleotide repeats in the Huntingtin gene (HTT) located on chromosome 4. It is transmitted in an autosomal dominant manner and is characterized by motor dysfunction, cognitive decline, and emotional disturbances. To date, there are no curative treatments for HD have been developed; current therapeutic approaches focus on symptom relief and comprehensive care through coordinated pharmacological and non-pharmacological methods to manage the diverse phenotypes of the disease. International clinical guidelines for the treatment of HD are continually being revised in an effort to enhance care within a multidisciplinary framework. Additionally, innovative gene and cell therapy strategies are being actively researched and developed to address the complexities of the disorder and improve treatment outcomes. This review endeavours to elucidate the current and emerging gene and cell therapy strategies for HD, offering a detailed insight into the complexities of the disorder and looking forward to future treatment paradigms. Considering the complexity of the underlying mechanisms driving HD, a synergistic treatment strategy that integrates various factors-such as distinct cell types, epigenetic patterns, genetic components, and methods to improve the cerebral microenvironment-may significantly enhance therapeutic outcomes. In the future, we eagerly anticipate ongoing innovations in interdisciplinary research that will bring profound advancements and refinements in the treatment of HD.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141910099","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