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Preserving genome integrity: The vital role of SUMO-targeted ubiquitin ligases 保存基因组完整性:sumo靶向泛素连接酶的重要作用
Cell insight Pub Date : 2023-10-23 DOI: 10.1016/j.cellin.2023.100128
Jinhua Han , Yanhua Mu , Jun Huang
{"title":"Preserving genome integrity: The vital role of SUMO-targeted ubiquitin ligases","authors":"Jinhua Han ,&nbsp;Yanhua Mu ,&nbsp;Jun Huang","doi":"10.1016/j.cellin.2023.100128","DOIUrl":"https://doi.org/10.1016/j.cellin.2023.100128","url":null,"abstract":"<div><p>Various post-translational modifications (PTMs) collaboratively fine-tune protein activities. SUMO-targeted ubiquitin E3 ligases (STUbLs) emerge as specialized enzymes that recognize SUMO-modified substrates through SUMO-interaction motifs and subsequently ubiquitinate them via the RING domain, thereby bridging the SUMO and ubiquitin signaling pathways. STUbLs participate in a wide array of molecular processes, including cell cycle regulation, DNA repair, replication, and mitosis, operating under both normal conditions and in response to challenges such as genotoxic stress. Their ability to catalyze various types of ubiquitin chains results in diverse proteolytic and non-proteolytic outcomes for target substrates. Importantly, STUbLs are strategically positioned in close proximity to SUMO proteases and deubiquitinases (DUBs), ensuring precise and dynamic control over their target proteins. In this review, we provide insights into the unique properties and indispensable roles of STUbLs, with a particular emphasis on their significance in preserving genome integrity in humans.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"2 6","pages":"Article 100128"},"PeriodicalIF":0.0,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772892723000524/pdfft?md5=d22991270a5d42822b520c6af5ca62eb&pid=1-s2.0-S2772892723000524-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92047509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of a thermostable Cas12a ortholog 耐热Cas12a同源物的表征
Cell insight Pub Date : 2023-10-11 DOI: 10.1016/j.cellin.2023.100126
Jing Wu , Pan Gao , Yajing Shi , Caixiang Zhang , Xiaohan Tong , Huidi Fan , Xi Zhou , Ying Zhang , Hao Yin
{"title":"Characterization of a thermostable Cas12a ortholog","authors":"Jing Wu ,&nbsp;Pan Gao ,&nbsp;Yajing Shi ,&nbsp;Caixiang Zhang ,&nbsp;Xiaohan Tong ,&nbsp;Huidi Fan ,&nbsp;Xi Zhou ,&nbsp;Ying Zhang ,&nbsp;Hao Yin","doi":"10.1016/j.cellin.2023.100126","DOIUrl":"https://doi.org/10.1016/j.cellin.2023.100126","url":null,"abstract":"<div><p>CRISPR-Cas12a has been used for genome editing and molecular diagnosis. The well-studied Cas12a orthologs have a T-rich PAM and are usually categorized as non-thermally stable enzymes. Here, we identified a new Cas12a ortholog from <em>Clostridium thermobutyricum</em>, which survives at 60 °C. This Cas12a ortholog is named as CtCas12a and exhibits low sequence similarity to the known Cas12a family members. CtCas12a is active in a wide temperature range from 17 to 77 °C. Moreover, this ortholog has a relaxed PAM of YYV (Y<img>C or T, V = A or C or G). We optimized the conditions for <em>trans</em>-cleavage and enabled its detection of nucleic acids. CtCas12a executed genome editing in human cells and generated up to 26% indel formation in the EGFP locus. With the ability to be active at high temperatures as well as having a relaxed PAM sequence, CtCas12a holds potential to be further engineered for pathogen detection and editing a wide range of genomic sequences.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"2 6","pages":"Article 100126"},"PeriodicalIF":0.0,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772892723000500/pdfft?md5=7000304e380e10671b49490e91b94225&pid=1-s2.0-S2772892723000500-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92047510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CPT1A mediates chemoresistance in human hypopharyngeal squamous cell carcinoma via ATG16L1-dependent cellular autophagy CPT1A通过ATG16L1依赖性细胞自噬介导人下咽鳞状细胞癌的化疗耐药性
Cell insight Pub Date : 2023-10-11 DOI: 10.1016/j.cellin.2023.100127
Lianhui Sun , Xing Wang , Lixiao Chen , Zheng Gao , Songhui Xu , Chen Hu , Guangjian Fan , Baoxin Wang , Tingting Feng , Wang Wang , Xinjiang Ying
{"title":"CPT1A mediates chemoresistance in human hypopharyngeal squamous cell carcinoma via ATG16L1-dependent cellular autophagy","authors":"Lianhui Sun ,&nbsp;Xing Wang ,&nbsp;Lixiao Chen ,&nbsp;Zheng Gao ,&nbsp;Songhui Xu ,&nbsp;Chen Hu ,&nbsp;Guangjian Fan ,&nbsp;Baoxin Wang ,&nbsp;Tingting Feng ,&nbsp;Wang Wang ,&nbsp;Xinjiang Ying","doi":"10.1016/j.cellin.2023.100127","DOIUrl":"https://doi.org/10.1016/j.cellin.2023.100127","url":null,"abstract":"<div><p>Hypopharyngeal squamous cell carcinoma (HSCC) is a highly aggressive malignancy that constitutes approximately 95% of all hypopharyngeal carcinomas, and it carries a poor prognosis. The primary factor influencing the efficacy of anti-cancer drugs for this type of carcinoma is chemoresistance. Carnitine palmitoyltransferase 1A (CPT1A) has been associated with tumor progression in various cancers, including breast, gastric, lung, and prostate cancer. The inhibition or depletion of CPT1A can lead to apoptosis, curbing cancer cell proliferation and chemoresistance. However, the role of CPT1A in HSCC is not yet fully understood. In this study, we discovered that CPT1A is highly expressed in HSCC and is associated with an advanced T-stage and a poor 5-year survival rate among patients. Furthermore, the overexpression of CPT1A contributes to HSCC chemoresistance. Mechanistically, CPT1A can interact with the autophagy-related protein ATG16L1 and stimulate the succinylation of ATG16L1, which in turn drives autophagosome formation and autophagy. We also found that treatment with 3-methyladenine (3-MA) can reduce cisplatin resistance in HSCC cells that overexpress CPT1A. Our findings also showed that a CPT1A inhibitor significantly enhances cisplatin sensitivity both in vitro and in vivo. This study is the first to suggest that CPT1A has a regulatory role in autophagy and is linked to poor prognosis in HSCC patients. It presents novel insights into the roles of CPT1A in tumorigenesis and proposes that CPT1A could be a potential therapeutic target for HSCC treatment.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"2 6","pages":"Article 100127"},"PeriodicalIF":0.0,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67739972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Salmonella infection acts as an environmental risk factor for human colon cancer 沙门氏菌感染是人类结肠癌的环境风险因素
Cell insight Pub Date : 2023-10-01 DOI: 10.1016/j.cellin.2023.100125
Erin B. Shanker , Jun Sun
{"title":"Salmonella infection acts as an environmental risk factor for human colon cancer","authors":"Erin B. Shanker ,&nbsp;Jun Sun","doi":"10.1016/j.cellin.2023.100125","DOIUrl":"https://doi.org/10.1016/j.cellin.2023.100125","url":null,"abstract":"<div><p>Emerging evidence has demonstrated that perturbations of host-microbial interactions by pathogens can lead to an altered microenvironment that promotes tumorigenesis. A recent study provides new evidence and mechanisms on how repetitive exposure to non-Typhoidal <em>Salmonella</em> (NTS) increases the risk for colon cancer. This study integrated a serological and epidemiological approach with both <em>in vivo</em> and <em>in vitro</em> analyses, showed that the magnitude of exposure to NTS is associated with colonic tumorigenesis. <em>In vivo</em> exposure to repetitive low doses of NTS led to colonic tumors similar as a single high NTS dose in mice. Repetitive NTS infections significantly increase the proliferation of transformed cells in tissue cultures. The research results open new possibilities for the diagnosis, prevention, and treatment of colon cancer. The unanswered questions remain, including validation of the current findings in other cohorts, differences in lifestyle, and changes of gut microbiome after <em>Salmonella</em> infection. <em>Salmonellae</em> exposure can be limited by eating cooked meats and washing vegetables well. It is necessary to develop guidelines and criteria for screenings and follow-ups in people with exposure history to <em>Salmonella</em> and other cancer-associated pathogens.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"2 5","pages":"Article 100125"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49774764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Arouse potential stemness: Intrinsic and acquired stem cell therapeutic strategies for advanced liver diseases 激发潜在的干细胞:内在和获得性干细胞治疗晚期肝脏疾病的策略
Cell insight Pub Date : 2023-10-01 DOI: 10.1016/j.cellin.2023.100115
Yisu Song , Zhengyang Lu , Wenzhi Shu , Ze Xiang , Zhengxin Wang , Xuyong Wei , Xiao Xu
{"title":"Arouse potential stemness: Intrinsic and acquired stem cell therapeutic strategies for advanced liver diseases","authors":"Yisu Song ,&nbsp;Zhengyang Lu ,&nbsp;Wenzhi Shu ,&nbsp;Ze Xiang ,&nbsp;Zhengxin Wang ,&nbsp;Xuyong Wei ,&nbsp;Xiao Xu","doi":"10.1016/j.cellin.2023.100115","DOIUrl":"10.1016/j.cellin.2023.100115","url":null,"abstract":"<div><p>Liver diseases are a major health issue, and prolonged liver injury always progresses. Advanced liver disorders impair liver regeneration. Millions of patients die yearly worldwide, even with the available treatments of liver transplantation and artificial liver support system. With its abundant cell resources and significant differentiative potential, stem cell therapy is a viable treatment for various disorders and offers hope to patients waiting for orthotopic liver transplantation. Considering such plight, stem cell therapeutic strategies deliver hope to the patients. Moreover, we conclude intrinsic and acquired perspectives based on stem cell sources. The properties and therapeutic uses of these stem cells' specific types or sources were then reviewed. Owing to the recent investigations of the above cells, a safe and effective therapy will emerge for advanced liver diseases soon.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"2 5","pages":"Article 100115"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/34/0f/main.PMC10502372.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10299941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mature white adipocyte plasticity during mammary gland remodelling and cancer 成熟的白色脂肪细胞在乳腺重塑和癌症过程中的可塑性。
Cell insight Pub Date : 2023-10-01 DOI: 10.1016/j.cellin.2023.100123
Parul Singh , Syed Azmal Ali
{"title":"Mature white adipocyte plasticity during mammary gland remodelling and cancer","authors":"Parul Singh ,&nbsp;Syed Azmal Ali","doi":"10.1016/j.cellin.2023.100123","DOIUrl":"10.1016/j.cellin.2023.100123","url":null,"abstract":"<div><p>Mammary gland growth and differentiation predominantly rely on stromal-epithelial cellular communication. Specifically, mammary adipocytes play a crucial role in ductal morphogenesis, as well as in the proliferation and differentiation of mammary epithelial cells. The process of lactation entails a reduction in the levels of white adipose tissue associated with the MG, allowing for the expansion of milk-producing epithelial cells. Subsequently, during involution and the regression of the milk-producing unit, adipocyte layers resurface, occupying the vacated space. This dynamic phenomenon underscores the remarkable plasticity and expansion of adipose tissue. Traditionally considered terminally differentiated, adipocytes have recently been found to exhibit plasticity in certain contexts. Unraveling the significance of this cell type within the MG could pave the way for novel approaches to reduce the risk of breast cancer and enhance lactation performance. Moreover, a comprehensive understanding of adipocyte <em>trans</em>- and de-differentiation processes holds promise for the development of innovative therapeutic interventions targeting cancer, fibrosis, obesity, type 2 diabetes, and other related diseases. Additionally, adipocytes may find utility in the realm of regenerative medicine. This review article provides a comprehensive examination of recent advancements in our understanding of MG remodelling, with a specific focus on the tissue-specific functions of adipocytes and their role in the development of cancer. By synthesizing current knowledge in this field, it aims to consolidate our understanding of adipocyte biology within the context of mammary gland biology, thereby fostering further research and discovery in this vital area.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"2 5","pages":"Article 100123"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b9/6a/main.PMC10522874.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41163101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cannabinoid receptor 2 signal promotes type 2 immunity in the lung 大麻酚受体2信号促进肺部的2型免疫。
Cell insight Pub Date : 2023-10-01 DOI: 10.1016/j.cellin.2023.100124
Tingting Liu , Jiaqi Liu , Hongjie Chen , Xin Zhou , Wei Fu , Ying Cao , Jing Yang
{"title":"Cannabinoid receptor 2 signal promotes type 2 immunity in the lung","authors":"Tingting Liu ,&nbsp;Jiaqi Liu ,&nbsp;Hongjie Chen ,&nbsp;Xin Zhou ,&nbsp;Wei Fu ,&nbsp;Ying Cao ,&nbsp;Jing Yang","doi":"10.1016/j.cellin.2023.100124","DOIUrl":"10.1016/j.cellin.2023.100124","url":null,"abstract":"<div><p>Type 2 immunity in the lung protects against pathogenic infection and facilitates tissue repair, but its dysregulation may lead to severe human diseases. Notably, cannabis usage for medical or recreational purposes has increased globally. However, the potential impact of the cannabinoid signal on lung immunity is incompletely understood. Here, we report that cannabinoid receptor 2 (CB2) is highly expressed in group 2 innate lymphoid cells (ILC2s) of mouse and human lung tissues. Of importance, the CB2 signal enhances the IL-33-elicited immune response of ILC2s. In addition, the chemogenetic manipulation of inhibitory G proteins (Gi) downstream of CB2 produces a similarly promotive effect. Conversely, the genetic deletion of CB2 mitigates the IL-33-elicited type 2 immunity in the lung. Also, such ablation of the CB2 signal ameliorates papain-induced tissue inflammation. Together, these results have elucidated a critical aspect of the CB2 signal in lung immunity, implicating its potential involvement in pulmonary diseases.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"2 5","pages":"Article 100124"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10585230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49694793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cover 封面
Cell insight Pub Date : 2023-10-01 DOI: 10.1016/S2772-8927(23)00053-6
{"title":"Cover","authors":"","doi":"10.1016/S2772-8927(23)00053-6","DOIUrl":"https://doi.org/10.1016/S2772-8927(23)00053-6","url":null,"abstract":"","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"2 5","pages":"Article 100129"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772892723000536/pdfft?md5=70e9c13d2d768701f2d035d0e741e27c&pid=1-s2.0-S2772892723000536-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91985509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Combatting persister cells: The daunting task in post-antibiotics era 对抗顽固细胞:后抗生素时代的艰巨任务
Cell insight Pub Date : 2023-08-01 DOI: 10.1016/j.cellin.2023.100104
Yidan Zhou , Hebin Liao , Linsen Pei , Yingying Pu
{"title":"Combatting persister cells: The daunting task in post-antibiotics era","authors":"Yidan Zhou ,&nbsp;Hebin Liao ,&nbsp;Linsen Pei ,&nbsp;Yingying Pu","doi":"10.1016/j.cellin.2023.100104","DOIUrl":"10.1016/j.cellin.2023.100104","url":null,"abstract":"<div><p>Over the years, much attention has been drawn to antibiotic resistance bacteria, but drug inefficacy caused by a subgroup of special phenotypic variants – persisters – has been largely neglected in both scientific and clinical field. Interestingly, this subgroup of phenotypic variants displayed their power of withstanding sufficient antibiotics exposure in a mechanism different from antibiotic resistance. In this review, we summarized the clinical importance of bacterial persisters, the evolutionary link between resistance, tolerance, and persistence, redundant mechanisms of persister formation as well as methods of studying persister cells. In the light of our recent findings of membrane-less organelle aggresome and its important roles in regulating bacterial dormancy depth, we propose an alternative approach for anti-persister therapy. That is, to force a persister into a deeper dormancy state to become a VBNC (viable but non-culturable) cell that is incapable of regrowth. We hope to provide the latest insights on persister studies and call upon more research interest into this field.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"2 4","pages":"Article 100104"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b5/49/main.PMC10250163.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9619503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
JMJD1B mediates H4R3me2s reprogramming to maintain DNA demethylation status in neural progenitor cells during embryonic development JMJD1B介导H4R3me2s重编程,以在胚胎发育过程中维持神经祖细胞中的DNA去甲基化状态。
Cell insight Pub Date : 2023-08-01 DOI: 10.1016/j.cellin.2023.100114
Li Zheng, Huifang Dai , Haitao Sun, Mian Zhou, Eric Zheng , Runxiang Qiu, Qiang Lu, Christina Wei, Binghui Shen
{"title":"JMJD1B mediates H4R3me2s reprogramming to maintain DNA demethylation status in neural progenitor cells during embryonic development","authors":"Li Zheng,&nbsp;Huifang Dai ,&nbsp;Haitao Sun,&nbsp;Mian Zhou,&nbsp;Eric Zheng ,&nbsp;Runxiang Qiu,&nbsp;Qiang Lu,&nbsp;Christina Wei,&nbsp;Binghui Shen","doi":"10.1016/j.cellin.2023.100114","DOIUrl":"10.1016/j.cellin.2023.100114","url":null,"abstract":"","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"2 4","pages":"Article 100114"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10448266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10111639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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