Protein & Cell最新文献_第8页

EZH2 in non-cancerous diseases: Expanding horizons. EZH2在非癌性疾病中的作用：拓展视野。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2025-05-19 DOI: 10.1093/procel/pwaf032

Renjing Jin,Jianlin Zhang,Yuqing Wang,Ziyu Chen,Xuan He,Xintong Zhang,Zhen Tan,Celina G Kleer,Ye Li,Deli Wang,Lixiang Xue

{"title":"EZH2 in non-cancerous diseases: Expanding horizons.","authors":"Renjing Jin,Jianlin Zhang,Yuqing Wang,Ziyu Chen,Xuan He,Xintong Zhang,Zhen Tan,Celina G Kleer,Ye Li,Deli Wang,Lixiang Xue","doi":"10.1093/procel/pwaf032","DOIUrl":"https://doi.org/10.1093/procel/pwaf032","url":null,"abstract":"Enhancer of Zeste homolog 2 (EZH2), a histone methyltransferase within polycomb repressive complex 2 (PRC2), plays a crucial role in epigenetic regulation by silencing gene expression through trimethylation of histone 3 at lysine 27 (H3K27me3). Beyond its well-documented oncogenic functions, emerging research has revealed EZH2's involvement in various non-cancerous pathologies. For instance, EZH2 is critical in regulating immune responses, particularly in modulating T cell differentiation and cytokine production, which affects inflammation and immune homeostasis. EZH2 also controls fibroblast activation and extracellular matrix (ECM) remodeling, influencing critical processes such as cell differentiation, tissue repair and energy homeostasis. Additionally, EZH2's epigenetic regulation of neuroinflammatory processes is linked to neuronal health and survival. Recent advancements in EZH2 inhibitor therapies demonstrate promising potential for treating a range of non-cancerous conditions, with preclinical trials suggesting efficacy in mitigating disease progression. This review highlights the expanding functional scope of EZH2, emphasizing its epigenetic mechanisms and the therapeutic opportunities for targeting EZH2 in non-cancerous diseases.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":"10 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087523","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

Glutamine signaling specifically activates c-Myc and Mcl-1 to Facilitate cancer cell proliferation and survival. 谷氨酰胺信号特异性激活c-Myc和Mcl-1促进癌细胞增殖和存活。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2025-05-04 DOI: 10.1093/procel/pwaf029

Meng Wang,Fu-Shen Guo,Dai-Sen Hou,Hui-Lu Zhang,Xiang-Tian Chen,Yan-Xin Shen,Zi-Fan Guo,Zhi-Fang Zheng,Yu-Peng Hu,Pei-Zhun Du,Chen-Ji Wang,Yan Lin,Yi-Yuan Yuan,Shi-Min Zhao,Wei Xu

{"title":"Glutamine signaling specifically activates c-Myc and Mcl-1 to Facilitate cancer cell proliferation and survival.","authors":"Meng Wang,Fu-Shen Guo,Dai-Sen Hou,Hui-Lu Zhang,Xiang-Tian Chen,Yan-Xin Shen,Zi-Fan Guo,Zhi-Fang Zheng,Yu-Peng Hu,Pei-Zhun Du,Chen-Ji Wang,Yan Lin,Yi-Yuan Yuan,Shi-Min Zhao,Wei Xu","doi":"10.1093/procel/pwaf029","DOIUrl":"https://doi.org/10.1093/procel/pwaf029","url":null,"abstract":"Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the seven substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase (QARS). Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":"25 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921014","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

Integrative transcriptomic and epigenomic analysis identifies BCL6B as a novel regulator of human pluripotent stem cell to endothelial differentiation. 综合转录组学和表观基因组学分析发现BCL6B是人类多能干细胞向内皮分化的一种新的调节因子。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2025-05-03 DOI: 10.1093/procel/pwaf039

Yonglin Zhu, Jinyang Liu, Jia Wang, Shuangyuan Ding, Hui Qiu, Xia Chen, Jianying Guo, Peiliang Wang, Xingwu Zhang, Fengzhi Zhang, Rujin Huang, Fuyu Duan, Lin Wang, Jie Na

引用次数: 0

CRISPR-based screening pinpoints H2AZ1 as a driver of senescence in human mesenchymal stem cells. 基于 CRISPR 的筛选确定 H2AZ1 是人类间充质干细胞衰老的驱动因素。

IF 12.8 1区生物学

Protein & Cell Pub Date : 2025-04-18 DOI: 10.1093/procel/pwae035

Ming-Heng Li, Xiaoyu Jiang, Yaobin Jing, Kaowen Yan, Shi-Jia Bi, Si Wang, Shuai Ma, Guang-Hui Liu, Weiqi Zhang, Shuhui Sun, Jing Qu

引用次数: 0

SMAD2/3-SMYD2 and developmental transcription factors cooperate with cell-cycle inhibitors to guide tissue formation. SMAD2/3-SMYD2 和发育转录因子与细胞周期抑制剂合作，引导组织形成。

IF 12.8 1区生物学

Protein & Cell Pub Date : 2025-04-18 DOI: 10.1093/procel/pwae031

Stefania Militi, Reshma Nibhani, Martin Pook, Siim Pauklin

{"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":"10.1093/procel/pwae031","url":null,"abstract":"Tissue formation and organ homeostasis are 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 signaling 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 of how cell-fate specification is interconnected to cell-cycle dynamics and provides insight into autonomous circuitries governing tissue self-formation.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"260-285"},"PeriodicalIF":12.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053477/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PKM2, the "K+ sink" in the tumor interstitial fluid. PKM2，肿瘤间质中的 "K+汇"。

IF 12.8 1区生物学

Protein & Cell Pub Date : 2025-04-18 DOI: 10.1093/procel/pwae036

Wenjing Na, Wenfeng Zeng, Kai Song, Youwang Wang, Luoyang Wang, Ziran Zhao, Lingtao Jin, Ping Zhu, Wei Liang

引用次数: 0

Skin organoid transplantation promotes tissue repair with scarless in frostbite. 皮肤类器官移植可促进冻伤组织的无疤痕修复。

IF 12.8 1区生物学

Protein & Cell Pub Date : 2025-04-18 DOI: 10.1093/procel/pwae055

Wenwen Wang, Pu Liu, Wendi Zhu, Tianwei Li, Ying Wang, Yujie Wang, Jun Li, Jie Ma, Ling Leng

{"title":"Skin organoid transplantation promotes tissue repair with scarless in frostbite.","authors":"Wenwen Wang, Pu Liu, Wendi Zhu, Tianwei Li, Ying Wang, Yujie Wang, Jun Li, Jie Ma, Ling Leng","doi":"10.1093/procel/pwae055","DOIUrl":"10.1093/procel/pwae055","url":null,"abstract":"Frostbite is the most common cold injury and is caused by both immediate cold-induced cell death and the gradual development of localized inflammation and tissue ischemia. Delayed healing of frostbite often leads to scar formation, which not only causes psychological distress but also tends to result in the development of secondary malignant tumors. Therefore, a rapid healing method for frostbite wounds is urgently needed. Herein, we used a mouse skin model of frostbite injury to evaluate the recovery process after frostbite. Moreover, single-cell transcriptomics was used to determine the patterns of changes in monocytes, macrophages, epidermal cells, and fibroblasts during frostbite. Most importantly, human-induced pluripotent stem cell (hiPSC)-derived skin organoids combined with gelatin-hydrogel were constructed for the treatment of frostbite. The results showed that skin organoid treatment significantly accelerated wound healing by reducing early inflammation after frostbite and increasing the proportions of epidermal stem cells. Moreover, in the later stage of wound healing, skin organoids reduced the overall proportions of fibroblasts, significantly reduced fibroblast-to-myofibroblast transition by regulating the integrin α5β1-FAK pathway, and remodeled the extracellular matrix (ECM) through degradation and reassembly mechanisms, facilitating the restoration of physiological ECM and reducing the abundance of ECM associated with abnormal scar formation. These results highlight the potential application of organoids for promoting the reversal of frostbite-related injury and the recovery of skin functions. This study provides a new therapeutic alternative for patients suffering from disfigurement and skin dysfunction caused by frostbite.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"240-259"},"PeriodicalIF":12.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372700","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

Secreted proteins in treating metabolic-dysfunction associated steatotic liver disease: from bench towards bedside. 分泌蛋白治疗代谢功能障碍相关的脂肪变性肝病：从实验室到床边。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2025-04-17 DOI: 10.1093/procel/pwaf027

Yeping Huang,Bin Liu,Cheng Hu,Yan Lu

{"title":"Secreted proteins in treating metabolic-dysfunction associated steatotic liver disease: from bench towards bedside.","authors":"Yeping Huang,Bin Liu,Cheng Hu,Yan Lu","doi":"10.1093/procel/pwaf027","DOIUrl":"https://doi.org/10.1093/procel/pwaf027","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a global epidemic, yet effective pharmacological treatments remain limited. Secreted proteins play diverse roles in regulating glucose and lipid metabolism, and their dysregulation is implicated in the development of various metabolic diseases, including MASLD. Therefore, targeting secreted proteins and modulating associated signaling pathways represents a promising therapeutic strategy for MASLD. In this review, we summarize recent findings on the roles of emerging families of secreted proteins in MASLD and related metabolic disorders. These include the orosomucoid (ORM) family, secreted acidic cysteine rich glycoprotein (SPARC) family, neuregulin (Nrg) family, growth differentiation factor (GDF) family, interleukin (IL) family, fibroblast growth factor (FGF) family, bone morphogenic protein (BMP) family, as well as isthmin-1 (Ism1) and mesencephalic astrocyte-derived neurotrophic factor (MANF). The review highlights their impact on glucose and lipid metabolism and discusses the clinical potential of targeting these secreted proteins as a therapeutic approach for MASLD.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":"34 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846284","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

The p15 protein is a promising immunogen for developing protective immunity against African swine fever virus. p15 蛋白是一种很有前景的免疫原，可用于开发针对非洲猪瘟病毒的保护性免疫。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2025-04-15 DOI: 10.1093/procel/pwaf026

Qi Yu,Wangjun Fu,Zhenjiang Zhang,Dening Liang,Lulu Wang,Yuanmao Zhu,Encheng Sun,Fang Li,Zhigao Bu,Yutao Chen,Xiangxi Wang,Dongming Zhao

引用次数: 0

Correction to: Chemical screen identifies a geroprotective role of quercetin in premature aging. 更正：化学筛选确定了槲皮素在早衰中的老年保护作用。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2025-03-29 DOI: 10.1093/procel/pwaf023

引用次数: 0