Protein & Cell最新文献

{"title":"Microbiota enterotoxigenic Bacteroides fragilis-secreted BFT-1 promotes breast cancer cell stemness and chemoresistance through its functional receptor NOD1.","authors":"Wei Ma, Lu Zhang, Weilong Chen, Zhaoxia Chang, Juchuanli Tu, Yuanyuan Qin, Yuwen Yao, Mengxue Dong, Jiajun Ding, Siqin Li, Fengkai Li, Qiaodan Deng, Yifei Yang, Tingting Feng, Fanrong Zhang, Xiying Shao, Xueyan He, Lixing Zhang, Guohong Hu, Quentin Liu, Yi-Zhou Jiang, Shu Zhu, Zhi Xiao, Dan Su, Tong Liu, Suling Liu","doi":"10.1093/procel/pwae005","DOIUrl":"10.1093/procel/pwae005","url":null,"abstract":"<p><p>Tumor-resident microbiota in breast cancer promotes cancer initiation and malignant progression. However, targeting microbiota to improve the effects of breast cancer therapy has not been investigated in detail. Here, we evaluated the microbiota composition of breast tumors and found that enterotoxigenic Bacteroides fragilis (ETBF) was highly enriched in the tumors of patients who did not respond to taxane-based neoadjuvant chemotherapy. ETBF, albeit at low biomass, secreted the toxic protein BFT-1 to promote breast cancer cell stemness and chemoresistance. Mechanistic studies showed that BFT-1 directly bound to NOD1 and stabilized NOD1 protein. NOD1 was highly expressed on ALDH+ breast cancer stem cells (BCSCs) and cooperated with GAK to phosphorylate NUMB and promote its lysosomal degradation, thereby activating the NOTCH1-HEY1 signaling pathway to increase BCSCs. NOD1 inhibition and ETBF clearance increase the chemosensitivity of breast cancer by impairing BCSCs.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"419-440"},"PeriodicalIF":13.6,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11131025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140022451","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}

{"title":"Immune rebalancing at the maternal-fetal interface of maternal SARS-CoV-2 infection during early pregnancy.","authors":"Chenxiang Xi, Zihui Yan, Dandan Bai, Yalin Zhang, Beiying Wang, Xiaoxiao Han, Li Wu, Xiaohui Shi, Zhiyi Hu, Ming Tang, Zhongqu Su, Yingdong Liu, Binya Liu, Jiqing Yin, Hong Wang, Xiaocui Li, Yanping Zhang, Shaorong Gao, Wenqiang Liu","doi":"10.1093/procel/pwae006","DOIUrl":"10.1093/procel/pwae006","url":null,"abstract":"<p><p>The current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) remains a threat to pregnant women. However, the impact of early pregnancy SARS-CoV-2 infection on the maternal-fetal interface remains poorly understood. Here, we present a comprehensive analysis of single-cell transcriptomics and metabolomics in placental samples infected with SARS-CoV-2 during early pregnancy. Compared to control placentas, SARS-CoV-2 infection elicited immune responses at the maternal-fetal interface and induced metabolic alterations in amino acid and phospholipid profiles during the initial weeks post-infection. However, subsequent immune cell activation and heightened immune tolerance in trophoblast cells established a novel dynamic equilibrium that mitigated the impact on the maternal-fetal interface. Notably, the immune response and metabolic alterations at the maternal-fetal interface exhibited a gradual decline during the second trimester. Our study underscores the adaptive immune tolerance mechanisms and establishment of immunological balance during the first two trimesters following maternal SARS-CoV-2 infection.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"460-473"},"PeriodicalIF":21.1,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11131034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140028839","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}

{"title":"SMAD2/3-SMYD2 and developmental transcription factors cooperate with cell cycle inhibitors to guide tissue formation.","authors":"Stefania Militi, Reshma Nibhani, Martin Pook, Siim Pauklin","doi":"10.1093/procel/pwae031","DOIUrl":"https://doi.org/10.1093/procel/pwae031","url":null,"abstract":"<p><p>Tissue formation and organ homeostasis is achieved by precise coordination of proliferation and differentiation of stem cells and progenitors. While deregulation of these processes can result in degenerative disease or cancer, their molecular interplays remain unclear. Here we show that the switch of human pluripotent stem cell (hPSC) self-renewal to differentiation is associated with the induction of distinct cyclin dependent kinase inhibitors (CDKIs). In hPSCs, Activin/Nodal/TGFβ signalling maintains CDKIs in a poised state via SMAD2/3-NANOG-OCT4-EZH2-SNON transcriptional complex. Upon gradual differentiation, CDKIs are induced by successive transcriptional complexes between SMAD2/3-SMYD2 and developmental regulators such as EOMES, thereby lengthening the G1 phase. This, in turn, induces SMAD2/3 transcriptional activity by blocking its linker phosphorylation. Such SMAD2/3-CDKI positive feedback loops drive the exit from pluripotency and stepwise cell fate specification that could be harnessed for producing cells for therapeutic applications. Our study uncovers fundamental mechanisms how cell fate specification is interconnected to cell cycle dynamics and provides insight to autonomous circuitries governing tissue self-formation.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":21.1,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959228","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}

{"title":"Exploring unconventional attributes of red blood cells and their potential applications in biomedicine.","authors":"Alkmini T Anastasiadi, Vasiliki-Zoi Arvaniti, Krystalyn E Hudson, Anastasios G Kriebardis, Constantinos Stathopoulos, Angelo D'Alessandro, Steven L Spitalnik, Vassilis L Tzounakas","doi":"10.1093/procel/pwae001","DOIUrl":"10.1093/procel/pwae001","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"315-330"},"PeriodicalIF":13.6,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547025","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}

{"title":"Applications of genetic code expansion technology in eukaryotes.","authors":"Qiao-Ru Guo, Yu J Cao","doi":"10.1093/procel/pwad051","DOIUrl":"10.1093/procel/pwad051","url":null,"abstract":"<p><p>Unnatural amino acids (UAAs) have gained significant attention in protein engineering and drug development owing to their ability to introduce new chemical functionalities to proteins. In eukaryotes, genetic code expansion (GCE) enables the incorporation of UAAs and facilitates posttranscriptional modification (PTM), which is not feasible in prokaryotic systems. GCE is also a powerful tool for cell or animal imaging, the monitoring of protein interactions in target cells, drug development, and switch regulation. Therefore, there is keen interest in utilizing GCE in eukaryotic systems. This review provides an overview of the application of GCE in eukaryotic systems and discusses current challenges that need to be addressed.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"331-363"},"PeriodicalIF":21.1,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41238103","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}

{"title":"Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics.","authors":"Huifen Lu, Ying Jing, Chen Zhang, Shuai Ma, Weiqi Zhang, Daoyuan Huang, Bin Zhang, Yuesheng Zuo, Yingying Qin, Guang-Hui Liu, Yang Yu, Jing Qu, Si Wang","doi":"10.1093/procel/pwad063","DOIUrl":"10.1093/procel/pwad063","url":null,"abstract":"<p><p>The ovary is indispensable for female reproduction, and its age-dependent functional decline is the primary cause of infertility. However, the molecular basis of ovarian aging in higher vertebrates remains poorly understood. Herein, we apply spatiotemporal transcriptomics to benchmark architecture organization as well as cellular and molecular determinants in young primate ovaries and compare these to aged primate ovaries. From a global view, somatic cells within the non-follicle region undergo more pronounced transcriptional fluctuation relative to those in the follicle region, likely constituting a hostile microenvironment that facilitates ovarian aging. Further, we uncovered that inflammation, the senescent-associated secretory phenotype, senescence, and fibrosis are the likely primary contributors to ovarian aging (PCOA). Of note, we identified spatial co-localization between a PCOA-featured spot and an unappreciated MT2 (Metallothionein 2) highly expressing spot (MT2high) characterized by high levels of inflammation, potentially serving as an aging hotspot in the primate ovary. Moreover, with advanced age, a subpopulation of MT2high accumulates, likely disseminating and amplifying the senescent signal outward. Our study establishes the first primate spatiotemporal transcriptomic atlas, advancing our understanding of mechanistic determinants underpinning primate ovarian aging and unraveling potential biomarkers and therapeutic targets for aging and age-associated human ovarian disorders.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"364-384"},"PeriodicalIF":21.1,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11075111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138831229","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}

{"title":"Correction to: Modeling CADASIL vascular pathologies with patient-derived induced pluripotent stem cells.","authors":"","doi":"10.1093/procel/pwad059","DOIUrl":"10.1093/procel/pwad059","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"393"},"PeriodicalIF":21.1,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138807224","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}

{"title":"Degeneration Directory: a multi-omics web resource for degenerative diseases.","authors":"Haoteng Yan, Changfa Lu, Chenyang Lan, Si Wang, Weiqi Zhang, Zan He, Jinghao Hu, Jiaqi Ai, Guang-Hui Liu, Shuai Ma, Yuanchun Zhou, Jing Qu","doi":"10.1093/procel/pwad066","DOIUrl":"10.1093/procel/pwad066","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"385-392"},"PeriodicalIF":13.6,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139049212","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}

{"title":"Senktide blocks aberrant RTN3 interactome to retard memory decline and tau pathology in social isolated Alzheimer's disease mice.","authors":"He-Zhou Huang, Wen-Qing Ai, Na Wei, Ling-Shuang Zhu, Zhi-Qiang Liu, Chao-Wen Zhou, Man-Fei Deng, Wen-Tao Zhang, Jia-Chen Zhang, Chun-Qing Yang, Ya-Zhuo Hu, Zhi-Tao Han, Hong-Hong Zhang, Jian-Jun Jia, Jing Wang, Fang-Fang Liu, Ke Li, Qi Xu, Mei Yuan, Hengye Man, Ziyuan Guo, Youming Lu, Kai Shu, Ling-Qiang Zhu, Dan Liu","doi":"10.1093/procel/pwad056","DOIUrl":"10.1093/procel/pwad056","url":null,"abstract":"<p><p>Sporadic or late-onset Alzheimer's disease (LOAD) accounts for more than 95% of Alzheimer's disease (AD) cases without any family history. Although genome-wide association studies have identified associated risk genes and loci for LOAD, numerous studies suggest that many adverse environmental factors, such as social isolation, are associated with an increased risk of dementia. However, the underlying mechanisms of social isolation in AD progression remain elusive. In the current study, we found that 7 days of social isolation could trigger pattern separation impairments and presynaptic abnormalities of the mossy fibre-CA3 circuit in AD mice. We also revealed that social isolation disrupted histone acetylation and resulted in the downregulation of 2 dentate gyrus (DG)-enriched miRNAs, which simultaneously target reticulon 3 (RTN3), an endoplasmic reticulum protein that aggregates in presynaptic regions to disturb the formation of functional mossy fibre boutons (MFBs) by recruiting multiple mitochondrial and vesicle-related proteins. Interestingly, the aggregation of RTN3 also recruits the PP2A B subunits to suppress PP2A activity and induce tau hyperphosphorylation, which, in turn, further elevates RTN3 and forms a vicious cycle. Finally, using an artificial intelligence-assisted molecular docking approach, we determined that senktide, a selective agonist of neurokinin3 receptors (NK3R), could reduce the binding of RTN3 with its partners. Moreover, application of senktide in vivo effectively restored DG circuit disorders in socially isolated AD mice. Taken together, our findings not only demonstrate the epigenetic regulatory mechanism underlying mossy fibre synaptic disorders orchestrated by social isolation and tau pathology but also reveal a novel potential therapeutic strategy for AD.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"261-284"},"PeriodicalIF":21.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10984625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138446012","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}

{"title":"Drug repurposing screening and mechanism analysis based on human colorectal cancer organoids.","authors":"Yunuo Mao, Wei Wang, Jingwei Yang, Xin Zhou, Yongqu Lu, Junpeng Gao, Xiao Wang, Lu Wen, Wei Fu, Fuchou Tang","doi":"10.1093/procel/pwad038","DOIUrl":"10.1093/procel/pwad038","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a highly heterogeneous cancer and exploring novel therapeutic options is a pressing issue that needs to be addressed. Here, we established human CRC tumor-derived organoids that well represent both morphological and molecular heterogeneities of original tumors. To efficiently identify repurposed drugs for CRC, we developed a robust organoid-based drug screening system. By combining the repurposed drug library and computation-based drug prediction, 335 drugs were tested and 34 drugs with anti-CRC effects were identified. More importantly, we conducted a detailed transcriptome analysis of drug responses and divided the drug response signatures into five representative patterns: differentiation induction, growth inhibition, metabolism inhibition, immune response promotion, and cell cycle inhibition. The anticancer activities of drug candidates were further validated in the established patient-derived organoids-based xenograft (PDOX) system in vivo. We found that fedratinib, trametinib, and bortezomib exhibited effective anticancer effects. Furthermore, the concordance and discordance of drug response signatures between organoids in vitro and pairwise PDOX in vivo were evaluated. Our study offers an innovative approach for drug discovery, and the representative transcriptome features of drug responses provide valuable resources for developing novel clinical treatments for CRC.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"285-304"},"PeriodicalIF":21.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10984622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9665176","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}