Protein & CellPub Date : 2024-10-01DOI: 10.1093/procel/pwae010
Dandan Feng, Jie Gao, Ruiqiong Liu, Wei Liu, Tianyang Gao, Yunkai Yang, Die Zhang, Tianshu Yang, Xin Yin, Hefen Yu, Wei Huang, Yan Wang
{"title":"CARM1 drives triple-negative breast cancer progression by coordinating with HIF1A.","authors":"Dandan Feng, Jie Gao, Ruiqiong Liu, Wei Liu, Tianyang Gao, Yunkai Yang, Die Zhang, Tianshu Yang, Xin Yin, Hefen Yu, Wei Huang, Yan Wang","doi":"10.1093/procel/pwae010","DOIUrl":"10.1093/procel/pwae010","url":null,"abstract":"<p><p>Coactivator-associated arginine methyltransferase 1 (CARM1) promotes the development and metastasis of estrogen receptor alpha (ERα)-positive breast cancer. The function of CARM1 in triple-negative breast cancer (TNBC) is still unclear and requires further exploration. Here, we report that CARM1 promotes proliferation, epithelial-mesenchymal transition, and stemness in TNBC. CARM1 is upregulated in multiple cancers and its expression correlates with breast cancer progression. Genome-wide analysis of CARM1 showed that CARM1 is recruited by hypoxia-inducible factor-1 subunit alpha (HIF1A) and occupy the promoters of CDK4, Cyclin D1, β-Catenin, HIF1A, MALAT1, and SIX1 critically involved in cell cycle, HIF-1 signaling pathway, Wnt signaling pathway, VEGF signaling pathway, thereby modulating the proliferation and invasion of TNBC cells. We demonstrated that CARM1 is physically associated with and directly interacts with HIF1A. Moreover, we found that ellagic acid, an inhibitor of CARM1, can suppress the proliferation and invasion of TNBC by directly inhibiting CDK4 expression. Our research has determined the molecular basis of CARM1 carcinogenesis in TNBC and its effective natural inhibitor, which may provide new ideas and drugs for cancer therapy.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"744-765"},"PeriodicalIF":13.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140111272","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":"NudCL2 is required for cytokinesis by stabilizing RCC2 with Hsp90 at the midbody.","authors":"Xiaoyang Xu, Yuliang Huang, Feng Yang, Xiaoxia Sun, Rijin Lin, Jiaxing Feng, Mingyang Yang, Jiaqi Shao, Xiaoqi Liu, Tianhua Zhou, Shanshan Xie, Yuehong Yang","doi":"10.1093/procel/pwae025","DOIUrl":"10.1093/procel/pwae025","url":null,"abstract":"<p><p>Cytokinesis is required for faithful division of cytoplasmic components and duplicated nuclei into two daughter cells. Midbody, a protein-dense organelle that forms at the intercellular bridge, is indispensable for successful cytokinesis. However, the regulatory mechanism of cytokinesis at the midbody still remains elusive. Here, we unveil a critical role for NudC-like protein 2 (NudCL2), a co-chaperone of heat shock protein 90 (Hsp90), in cytokinesis regulation by stabilizing regulator of chromosome condensation 2 (RCC2) at the midbody in mammalian cells. NudCL2 localizes at the midbody, and its downregulation results in cytokinesis failure, multinucleation, and midbody disorganization. Using iTRAQ-based quantitative proteomic analysis, we find that RCC2 levels are decreased in NudCL2 knockout (KO) cells. Moreover, Hsp90 forms a complex with NudCL2 to stabilize RCC2, which is essential for cytokinesis. RCC2 depletion mirrors phenotypes observed in NudCL2-downregulated cells. Importantly, ectopic expression of RCC2 rescues the cytokinesis defects induced by NudCL2 deletion, but not vice versa. Together, our data reveal the significance of the NudCL2/Hsp90/RCC2 pathway in cytokinesis at the midbody.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"766-782"},"PeriodicalIF":13.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154676","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}
Protein & CellPub Date : 2024-09-27DOI: 10.1093/procel/pwae053
Xiufang Xiong,Yongchao Zhao,Yi Sun
{"title":"SMURF1: A promising target for colon cancer therapy.","authors":"Xiufang Xiong,Yongchao Zhao,Yi Sun","doi":"10.1093/procel/pwae053","DOIUrl":"https://doi.org/10.1093/procel/pwae053","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":"36 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142329093","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":"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":"48 1","pages":""},"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}
Protein & CellPub Date : 2024-09-01DOI: 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":"<p><p>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.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"661-685"},"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}
Protein & CellPub Date : 2024-09-01DOI: 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
{"title":"Proteomic analysis of ferroptosis pathways reveals a role of CEPT1 in suppressing ferroptosis.","authors":"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","doi":"10.1093/procel/pwae004","DOIUrl":"10.1093/procel/pwae004","url":null,"abstract":"<p><p>Ferroptosis has been recognized as a unique cell death modality driven by excessive lipid peroxidation and unbalanced cellular metabolism. In this study, we established a protein interaction landscape for ferroptosis pathways through proteomic analyses, and identified choline/ethanolamine phosphotransferase 1 (CEPT1) as a lysophosphatidylcholine acyltransferase 3 (LPCAT3)-interacting protein that regulates LPCAT3 protein stability. In contrast to its known role in promoting phospholipid synthesis, we showed that CEPT1 suppresses ferroptosis potentially by interacting with phospholipases and breaking down certain pro-ferroptotic polyunsaturated fatty acid (PUFA)-containing phospholipids. Together, our study reveals a previously unrecognized role of CEPT1 in suppressing ferroptosis.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"686-703"},"PeriodicalIF":13.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11365556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140022452","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}
Protein & CellPub Date : 2024-09-01DOI: 10.1093/procel/pwae003
Chao Mao, Min Wang, Li Zhuang, Boyi Gan
{"title":"Metabolic cell death in cancer: ferroptosis, cuproptosis, disulfidptosis, and beyond.","authors":"Chao Mao, Min Wang, Li Zhuang, Boyi Gan","doi":"10.1093/procel/pwae003","DOIUrl":"10.1093/procel/pwae003","url":null,"abstract":"<p><p>Cell death resistance represents a hallmark of cancer. Recent studies have identified metabolic cell death as unique forms of regulated cell death resulting from an imbalance in the cellular metabolism. This review discusses the mechanisms of metabolic cell death-ferroptosis, cuproptosis, disulfidptosis, lysozincrosis, and alkaliptosis-and explores their potential in cancer therapy. Our review underscores the complexity of the metabolic cell death pathways and offers insights into innovative therapeutic avenues for cancer treatment.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"642-660"},"PeriodicalIF":13.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11365558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013244","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}