Cell and Bioscience最新文献

{"title":"Organoid as a promising tool for primary liver cancer research: a comprehensive review.","authors":"Xuekai Hu, Jiayun Wei, Pinyan Liu, Qiuxia Zheng, Yue Zhang, Qichen Zhang, Jia Yao, Jingman Ni","doi":"10.1186/s13578-024-01287-5","DOIUrl":"10.1186/s13578-024-01287-5","url":null,"abstract":"<p><p>Primary liver cancer (PLC) is one of the most common malignant gastrointestinal tumors worldwide. Limited by the shortage of liver transplantation donors and the heterogeneity of tumors, patients with liver cancer lack effective treatment options, which leads to rapid progression and metastasis. Currently, preclinical models of PLC fall short of clinical reality and are limited in their response to disease progression and the effectiveness of drug therapy. Organoids are in vitro three-dimensional cultured preclinical models with a high degree of heterogeneity that preserve the histomorphological and genomic features of primary tumors. Liver cancer organoids have been widely used for drug screening, new target discovery, and precision medicine; thus representing a promising tool to study PLC. Here, we summarize the progress of research on liver cancer organoids and their potential application as disease models. This review provides a comprehensive introduction to this emerging technology and offers new ideas for researchers to explore in the field of precision medicine.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"14 1","pages":"107"},"PeriodicalIF":6.1,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into the m⁶A demethylases FTO and ALKBH5 : structural, biological function, and inhibitor development.","authors":"Zewei Gao, Xuan Zha, Min Li, Xueli Xia, Shengjun Wang","doi":"10.1186/s13578-024-01286-6","DOIUrl":"10.1186/s13578-024-01286-6","url":null,"abstract":"<p><p>N6-methyladenosine (m⁶A) is dynamically regulated by methyltransferases (termed \"writers\") and demethylases (referred to as \"erasers\"), facilitating a reversible modulation. Changes in m⁶A levels significantly influence cellular functions, such as RNA export from the nucleus, mRNA metabolism, protein synthesis, and RNA splicing. They are intricately associated with a spectrum of pathologies. Moreover, dysregulation of m⁶A modulation has emerged as a promising therapeutic target across many diseases. m⁶A plays a pivotal role in controlling vital downstream molecules and critical biological pathways, contributing to the pathogenesis and evolution of numerous conditions. This review provides an overview of m⁶A demethylases, explicitly detailing the structural and functional characteristics of FTO and ALKBH5. Additionally, we explore their distinct involvement in various diseases, examine factors regulating their expression, and discuss the progress in inhibitor development.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"14 1","pages":"108"},"PeriodicalIF":6.1,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11351023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduction of eEF2 kinase alleviates the learning and memory impairment caused by acrylamide.","authors":"Xiao-Li Wang, Ru-Nan Zhang, Yu-Lin Pan, Zhi-Ming Li, Hong-Qiu Li, Ya-Ting Lei, Fang-Fang Zhao, Xiao-Xiao Hao, Wei-Wei Ma, Cui-Ping Yu, Hong-Wei Yao, Xin-Yu Wang, Jun-Jie Lv, Yong-Hui Wu, Sheng-Yuan Wang","doi":"10.1186/s13578-024-01285-7","DOIUrl":"10.1186/s13578-024-01285-7","url":null,"abstract":"<p><strong>Background: </strong>The impact of acrylamide (ACR) on learning and memory has garnered considerable attention. However, the targets and mechanisms are still unclear.</p><p><strong>Results: </strong>Elongation factor 2 (eEF2) was significantly upregulated in the results of serum proteomics. Results from in vitro and in vivo experiments indicated a notable upregulation of Eukaryotic elongation factor 2 kinase (eEF2K), the sole kinase responsible for eEF2 phosphorylation, following exposure to ACR (P < 0.05). Subsequent in vitro experiments using eEF2K siRNA and in vivo experiments with eEF2K-knockout mice demonstrated significant improvements in abnormal indicators related to ACR-induced learning and memory deficits (P < 0.05). Proteomic analysis of the hippocampus revealed Lpcat1 as a crucial downstream protein regulated by eEF2K. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that eEF2K may play a role in the process of ACR-induced learning and memory impairment by affecting ether lipid metabolism.</p><p><strong>Conclusions: </strong>In summary, eEF2K as a pivotal treatment target in the mechanisms underlying ACR-induced learning and memory impairment, and studies have shown that it provides robust evidence for potential clinical interventions targeting ACR-induced impairments.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"14 1","pages":"106"},"PeriodicalIF":6.1,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signaling pathways activated and regulated by stem cell-derived exosome therapy.","authors":"Ding Li, Danni Li, Zhao Wang, Jiaojiao Li, Khawar Ali Shahzad, Yanhong Wang, Fei Tan","doi":"10.1186/s13578-024-01277-7","DOIUrl":"10.1186/s13578-024-01277-7","url":null,"abstract":"<p><p>Stem cell-derived exosomes exert comparable therapeutic effects to those of their parental stem cells without causing immunogenic, tumorigenic, and ethical disadvantages. Their therapeutic advantages are manifested in the management of a broad spectrum of diseases, and their dosing versatility are exemplified by systemic administration and local delivery. Furthermore, the activation and regulation of various signaling cascades have provided foundation for the claimed curative effects of exosomal therapy. Unlike other relevant reviews focusing on the upstream aspects (e.g., yield, isolation, modification), and downstream aspects (e.g. phenotypic changes, tissue response, cellular behavior) of stem cell-derived exosome therapy, this unique review endeavors to focus on various affected signaling pathways. After meticulous dissection of relevant literature from the past five years, we present this comprehensive, up-to-date, disease-specific, and pathway-oriented review. Exosomes sourced from various types of stem cells can regulate major signaling pathways (e.g., the PTEN/PI3K/Akt/mTOR, NF-κB, TGF-β, HIF-1α, Wnt, MAPK, JAK-STAT, Hippo, and Notch signaling cascades) and minor pathways during the treatment of numerous diseases encountered in orthopedic surgery, neurosurgery, cardiothoracic surgery, plastic surgery, general surgery, and other specialties. We provide a novel perspective in future exosome research through bridging the gap between signaling pathways and surgical indications when designing further preclinical studies and clinical trials.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"14 1","pages":"105"},"PeriodicalIF":6.1,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lack of basic rationale in epithelial-mesenchymal transition and its related concepts.","authors":"Ying Cao","doi":"10.1186/s13578-024-01282-w","DOIUrl":"10.1186/s13578-024-01282-w","url":null,"abstract":"<p><p>Epithelial-mesenchymal transition (EMT) is defined as a cellular process during which epithelial cells acquire mesenchymal phenotypes and behavior following the downregulation of epithelial features. EMT and its reversed process, the mesenchymal-epithelial transition (MET), and the special form of EMT, the endothelial-mesenchymal transition (EndMT), have been considered as mainstream concepts and general rules driving developmental and pathological processes, particularly cancer. However, discrepancies and disputes over EMT and EMT research have also grown over time. EMT is defined as transition between two cellular states, but it is unanimously agreed by EMT researchers that (1) neither the epithelial and mesenchymal states nor their regulatory networks have been clearly defined, (2) no EMT markers or factors can represent universally epithelial and mesenchymal states, and thus (3) EMT cannot be assessed on the basis of one or a few EMT markers. In contrast to definition and proposed roles of EMT, loss of epithelial feature does not cause mesenchymal phenotype, and EMT does not contribute to embryonic mesenchyme and neural crest formation, the key developmental events from which the EMT concept was derived. EMT and MET, represented by change in cell shapes or adhesiveness, or symbolized by EMT factors, are biased interpretation of the overall change in cellular property and regulatory networks during development and cancer progression. Moreover, EMT and MET are consequences rather than driving factors of developmental and pathological processes. The true meaning of EMT in some developmental and pathological processes, such as fibrosis, needs re-evaluation. EMT is believed to endow malignant features, such as migration, stemness, etc., to cancer cells. However, the core property of cancer (tumorigenic) cells is neural stemness, and the core EMT factors are components of the regulatory networks of neural stemness. Thus, EMT in cancer progression is misattribution of the roles of neural stemness to the unknown mesenchymal state. Similarly, neural crest EMT is misattribution of intrinsic property of neural crest cells to the unknown mesenchymal state. Lack of basic rationale in EMT and related concepts urges re-evaluation of their significance as general rules for understanding developmental and pathological processes, and re-evaluation of their significance in scientific research.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"14 1","pages":"104"},"PeriodicalIF":6.1,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SOX2 interacts with hnRNPK to modulate alternative splicing in mouse embryonic stem cells.","authors":"Yanlan Huang, Yuxuan Liu, Mingyi Pu, Yuli Zhang, Qiang Cao, Senru Li, Yuanjie Wei, Linlin Hou","doi":"10.1186/s13578-024-01284-8","DOIUrl":"10.1186/s13578-024-01284-8","url":null,"abstract":"<p><strong>Background: </strong>SOX2 is a determinant transcription factor that governs the balance between stemness and differentiation by influencing transcription and splicing programs. The role of SOX2 is intricately shaped by its interactions with specific partners. In the interactome of SOX2 in mouse embryonic stem cells (mESCs), there is a cohort of heterogeneous nuclear ribonucleoproteins (hnRNPs) that contributes to multiple facets of gene expression regulation. However, the cross-talk between hnRNPs and SOX2 in gene expression regulation remains unclear.</p><p><strong>Results: </strong>Here we demonstrate the indispensable role of the co-existence of SOX2 and heterogeneous nuclear ribonucleoprotein K (hnRNPK) in the maintenance of pluripotency in mESCs. While hnRNPK directly interacts with the SOX2-HMG DNA-binding domain and induces the collapse of the transcriptional repressor 7SK small nuclear ribonucleoprotein (7SK snRNP), hnRNPK does not influence SOX2-mediated transcription, either by modulating the interaction between SOX2 and its target cis-regulatory elements or by facilitating transcription elongation as indicated by the RNA-seq analysis. Notably, hnRNPK enhances the interaction of SOX2 with target pre-mRNAs and collaborates with SOX2 in regulating the alternative splicing of a subset of pluripotency genes.</p><p><strong>Conclusions: </strong>These data reveal that SOX2 and hnRNPK have a direct protein-protein interaction, and shed light on the molecular mechanisms by which hnRNPK collaborates with SOX2 in alternative splicing in mESCs.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"14 1","pages":"102"},"PeriodicalIF":6.1,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11331657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The tripartite motif-containing 24 is a multifunctional player in human cancer.","authors":"Yuanbing Yao, Sheng Zhou, Yue Yan, Kai Fu, Shuai Xiao","doi":"10.1186/s13578-024-01289-3","DOIUrl":"10.1186/s13578-024-01289-3","url":null,"abstract":"<p><p>Tripartite motif-containing 24 (TRIM24), also known as transcriptional intermediary factor 1α (TIF1α), is the founding member of TIF1 family. Recent evidence indicates that aberrant expression of TRIM24, functions as an oncogene, is associated with poor prognosis across various cancer types. TRIM24 exhibits a multifaceted structure comprising an N-terminal TRIM region with a RING domain, B-box type 1 and type 2 domains, and a coiled-coil region, as well as a C-terminal plant-homeodomain (PHD)-bromodomain. The bromodomain serves as a 'reader' of epigenetic histone marks, regulating chromatin structure and gene expression by linking associated proteins to acetylated nucleosomal targets, thereby controlling transcription of genes. Notably, bromodomains have emerged as compelling targets for cancer therapeutic development. In addition, TRIM24 plays specialized roles as a signal transduction molecule, orchestrating various cellular signaling cascades in cancer cells. Herein, we review the recent advancements in understanding the functions of TRIM24, and demonstrate the research progress in utilizing TRIM24 as a target for cancer therapy.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"14 1","pages":"103"},"PeriodicalIF":6.1,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 variants divergently infect and damage cardiomyocytes in vitro and in vivo.","authors":"Bobo Wing-Yee Mok, Maxwell Kwok, Hung Sing Li, Lowell Ling, Angel Lai, Bin Yan, Cherie Tsz-Yiu Law, Chui Him Yeung, Anna Jinxia Zhang, Rachel Chun-Yee Tam, Anja Kukic, Conor J Cremin, Yajie Zhang, Teng Long, Zhisen Kang, Ruibang Luo, Kam Tong Leung, Albert M Li, Grace Lui, Stephen Kwok-Wing Tsui, Jasper Fuk-Woo Chan, Kelvin Kai-Wang To, Paul K S Chan, Bryan P Yan, Honglin Chen, Ellen Ngar-Yun Poon","doi":"10.1186/s13578-024-01280-y","DOIUrl":"10.1186/s13578-024-01280-y","url":null,"abstract":"<p><strong>Background: </strong>COVID-19 can cause cardiac complications and the latter are associated with poor prognosis and increased mortality. SARS-CoV-2 variants differ in their infectivity and pathogenicity, but how they affect cardiomyocytes (CMs) is unclear.</p><p><strong>Methods: </strong>The effects of SARS-CoV-2 variants were investigated using human induced pluripotent stem cell-derived (hiPSC-) CMs in vitro and Golden Syrian hamsters in vivo.</p><p><strong>Results: </strong>Different variants exhibited distinct tropism, mechanism of viral entry and pathology in the heart. Omicron BA.2 most efficiently infected and injured CMs in vitro and in vivo, and induced expression changes consistent with increased cardiac dysfunction, compared to other variants tested. Bioinformatics and upstream regulator analyses identified transcription factors and network predicted to control the unique transcriptome of Omicron BA.2 infected CMs. Increased infectivity of Omicron BA.2 is attributed to its ability to infect via endocytosis, independently of TMPRSS2, which is absent in CMs.</p><p><strong>Conclusions: </strong>In this study, we reveal previously unknown differences in how different SARS-CoV-2 variants affect CMs. Omicron BA.2, which is generally thought to cause mild disease, can damage CMs in vitro and in vivo. Our study highlights the need for further investigations to define the pathogenesis of cardiac complications arising from different SARS-CoV-2 variants.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"14 1","pages":"101"},"PeriodicalIF":6.1,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dihydroartemisinin restores the immunogenicity and enhances the anticancer immunosurveillance of cisplatin by activating the PERK/eIF2α pathway.","authors":"Yumei Li, Pei Ma, Jingxia Li, Feng Wu, Mengfei Guo, E Zhou, Siwei Song, Sufei Wang, Shuai Zhang, Yang Jin","doi":"10.1186/s13578-024-01254-0","DOIUrl":"10.1186/s13578-024-01254-0","url":null,"abstract":"<p><strong>Background: </strong>Immunosurveillance is pivotal in the effectiveness of anticancer therapies and tumor control. The ineffectiveness of cisplatin in activating the immunosurveillance is attributed to its lack of adjuvanticity resulting from its inability to stimulate endoplasmic reticulum stress. Dihydroartemisinin demonstrates the anti-tumor effects through various mechanisms, including the activation of the endoplasmic reticulum stress. This study aimed to develop a novel strategy to enhance the immunogenicity of dying tumor cells by combining cisplatin with dihydroartemisinin, thereby triggering effective anti-tumor immunosurveillance and improving the efficacy of cisplatin in clinical practice.</p><p><strong>Methods: </strong>Lewis lung carcinoma (LLC) and CT26 colon cancer cell lines and subcutaneous tumor models were used in this study. The importance of immunosurveillance was validated in both immunocompetent and immunodeficient mouse models. The ability of dihydroartemisinin and cisplatin therapy to induce immunogenic cell death and tumor growth control in vivo was validated by prophylactic tumor vaccination and therapeutic tumor models. The underlying mechanism was elucidated through the pharmaceutical or genetic intervention of the PERK/eIF2α pathway in vitro and in vivo.</p><p><strong>Results: </strong>Dihydroartemisinin enhanced the generation of reactive oxygen species in cisplatin-treated LLC and CT26 cancer cells. The combination treatment of dihydroartemisinin with cisplatin promoted cell death and ensured an optimal release of damage-associated molecular patterns from dying cancer cells, promoting the phagocytosis of dendritic cells. In the tumor vaccination model, we confirmed that dihydroartemisinin plus cisplatin treatment induced immunogenic cell death. Utilizing immunocompetent and immunodeficient mouse models, we further demonstrated that the combination treatment suppressed the tumor growth of CT26 colon cancer and LLC lung cancer, leading to an improved prognosis through the restoration of cytotoxic T lymphocyte responses and reinstatement of anti-cancer immunosurveillance in vivo. Mechanistically, dihydroartemisinin restored the immunogenicity of cisplatin by activating the adjuvanticity of damage-associated molecular patterns, such as calreticulin exposure, through the PERK/eIF2α pathway. Additionally, the inhibition of eIF2α phosphorylation attenuated the anti-tumor efficiency of C + D in vivo.</p><p><strong>Conclusions: </strong>We highlighted that dihydroartemisinin acts as an immunogenic cell death rescuer for cisplatin, activating anticancer immunosurveillance in a PERK/eIF2α-dependent manner and offering a strategy to enhance the anti-tumor efficacy of cisplatin in clinical practice.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"14 1","pages":"100"},"PeriodicalIF":6.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11295430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PDLIM2 is a novel E5 ubiquitin ligase enhancer that stabilizes ROC1 and recruits the ROC1-SCF ubiquitin ligase to ubiquitinate and degrade NF-κB RelA.","authors":"Fan Sun, Gutian Xiao, Zhaoxia Qu","doi":"10.1186/s13578-024-01281-x","DOIUrl":"10.1186/s13578-024-01281-x","url":null,"abstract":"<p><p>The PDZ-LIM domain-containing protein PDLIM2 is a common tumor suppressor and a key immune modulator. One main function of PDLIM2 is to promote the ubiquitination and proteasomal degradation of nuclear activated NF-κB RelA, a physiologically indispensable transcription factor whose persistent activation has been linked to almost all cancer types and inflammation-associated diseases. However, it remains unknown how PDLIM2 exerts this physiologically and pathogenically important function. Here, we show that PDLIM2 acts as a ubiquitin ligase enhancer, termed E5. It stabilizes ROC1, an essential component of SKP1/Cullin/F-box protein (SCF) ubiquitin ligases, and chaperones the ROC1-SCF^β-TrCP ubiquitin ligase to ubiquitinate nuclear RelA for proteasomal degradation in the nucleus. Consistently, silencing of ROC1, Cullin 1 or the F-box protein β-TrCP blocks RelA ubiquitination and degradation by PDLIM2. These data provide new mechanistic insights into how PDLIM2 promotes nuclear RelA ubiquitination and degradation, thereby serving as a critical tumor suppressor and a vital immune regulator. They also improve our understanding of the complex cascade of the ubiquitination and NF-κB pathways, particularly given the well-known role of the ROC1-SCF^β-TrCP ubiquitin ligase in initiating NF-κB activation by directly binding to and ubiquitinating NF-κB inhibitors for the proteasomal degradation in the cytoplasm.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"14 1","pages":"99"},"PeriodicalIF":6.1,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}