Molecules and Cells最新文献_第10页

Senotherapeutics: Different approaches of discovery and development Senotherapeutics：发现和开发的不同方法

IF 3.8 3区生物学

Molecules and Cells Pub Date : 2024-01-01 DOI: 10.1016/j.mocell.2023.10.001

Jee Hyeon Yoon, Ho Jae Han

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Cover 封面

IF 3.8 3区生物学

Molecules and Cells Pub Date : 2024-01-01 DOI: 10.1016/S1016-8478(24)00021-9

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Editorial Board Members/Copyright 编委会成员/版权

IF 3.8 3区生物学

Molecules and Cells Pub Date : 2024-01-01 DOI: 10.1016/S1016-8478(24)00022-0

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N-recognins UBR1 and UBR2 as central ER stress sensors in mammals 作为哺乳动物ER应激中心传感器的N-识别蛋白UBR1和UBR2

IF 3.8 3区生物学

Molecules and Cells Pub Date : 2024-01-01 DOI: 10.1016/j.mocell.2023.12.001

Ly Thi Huong Luu Le , Seoyoung Park , Jung Hoon Lee , Yun Kyung Kim , Min Jae Lee

{"title":"N-recognins UBR1 and UBR2 as central ER stress sensors in mammals","authors":"Ly Thi Huong Luu Le , Seoyoung Park , Jung Hoon Lee , Yun Kyung Kim , Min Jae Lee","doi":"10.1016/j.mocell.2023.12.001","DOIUrl":"https://doi.org/10.1016/j.mocell.2023.12.001","url":null,"abstract":"<div>In eukaryotes, a primary protein quality control (PQC) process involves the destruction of conformationally misfolded proteins through the ubiquitin-proteasome system. Because approximately one-third of eukaryotic proteomes fold and assemble within the endoplasmic reticulum (ER) before being sent to their destinations, the ER plays a crucial role in PQC. The specific functions and biochemical roles of several E3 ubiquitin ligases involved in ER-associated degradation in mammals, on the other hand, are mainly unknown. We identified 2 E3 ligases, ubiquitin protein ligase E3 component N-recognin 1 (UBR1) and ubiquitin protein ligase E3 component N-recognin 2 (UBR2), which are the key N-recognins in the N-degron pathway and participate in the ER stress response in mammalian cells by modulating their stability. Cells lacking UBR1 and UBR2 are hypersensitive to ER stress-induced apoptosis. Under normal circumstances, these proteins are polyubiquitinated through Lys48-specific linkages and are then degraded by the 26S proteasome. In contrast, when cells are subjected to ER stress, UBR1 and UBR2 exhibit greater stability, potentially as a cellular adaptive response to stressful conditions. Although the precise mechanisms underlying these findings require further investigation, our findings show that cytoplasmic UBR1 and UBR2 have anti-ER stress activities and contribute to global PQC in mammals. These data also reveal an additional level of complexity within the mammalian ER-associated degradation system, implicating potential involvement of the N-degron pathway.</div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1016847823252516/pdfft?md5=2ffc37393cc2fae03b76029382992386&pid=1-s2.0-S1016847823252516-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139674456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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A comparison study of pathological features and drug efficacy between Drosophila models of C9orf72 ALS/FTD C9orf72 ALS/FTD果蝇模型病理特征和药物疗效比较研究

IF 3.8 3区生物学

Molecules and Cells Pub Date : 2024-01-01 DOI: 10.1016/j.mocell.2023.12.003

Davin Lee , Hae Chan Jeong , Seung Yeol Kim , Jin Yong Chung , Seok Hwan Cho , Kyoung Ah Kim , Jae Ho Cho , Byung Su Ko , In Jun Cha , Chang Geon Chung , Eun Seon Kim , Sung Bae Lee

{"title":"A comparison study of pathological features and drug efficacy between Drosophila models of C9orf72 ALS/FTD","authors":"Davin Lee , Hae Chan Jeong , Seung Yeol Kim , Jin Yong Chung , Seok Hwan Cho , Kyoung Ah Kim , Jae Ho Cho , Byung Su Ko , In Jun Cha , Chang Geon Chung , Eun Seon Kim , Sung Bae Lee","doi":"10.1016/j.mocell.2023.12.003","DOIUrl":"10.1016/j.mocell.2023.12.003","url":null,"abstract":"<div>Amyotrophic lateral sclerosis is a devastating neurodegenerative disease with a complex genetic basis, presenting both in familial and sporadic forms. The hexanucleotide (G4C2) repeat expansion in the C9orf72 gene, which triggers distinct pathogenic mechanisms, has been identified as a major contributor to familial and sporadic Amyotrophic lateral sclerosis cases. Animal models have proven pivotal in understanding these mechanisms; however, discrepancies between models due to variable transgene sequence, expression levels, and toxicity profiles complicate the translation of findings. Herein, we provide a systematic comparison of 7 publicly available Drosophila transgenes modeling the G4C2 expansion under uniform conditions, evaluating variations in their toxicity profiles. Further, we tested 3 previously characterized disease-modifying drugs in selected lines to uncover discrepancies among the tested strains. Our study not only deepens our understanding of the C9orf72 G4C2 mutations but also presents a framework for comparing constructs with minute structural differences. This work may be used to inform experimental designs to better model disease mechanisms and help guide the development of targeted interventions for neurodegenerative diseases, thus bridging the gap between model-based research and therapeutic application.</div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1016847823252553/pdfft?md5=e4596f25be7da1494d88758f2706ac9b&pid=1-s2.0-S1016847823252553-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139014078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Beethoven, Infected with Hepatitis B, Inspired the "Beethoven Virus." 贝多芬感染乙肝，激发了 "贝多芬病毒"。

IF 3.8 3区生物学

Molecules and Cells Pub Date : 2023-12-31 Epub Date: 2023-10-20 DOI: 10.14348/molcells.2023.0132

Sun-Kyung Lee, Seung Hyun Kim, Joohong Ahnn

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Novel Anti-Mesothelin Nanobodies and Recombinant Immunotoxins with Pseudomonas Exotoxin Catalytic Domain for Cancer Therapeutics. 用于癌症治疗的新型抗外皮生长因子纳米抗体和具有假单胞菌毒素催化域的重组免疫毒素。

IF 3.8 3区生物学

Molecules and Cells Pub Date : 2023-12-31 Epub Date: 2023-12-01 DOI: 10.14348/molcells.2023.0155

Minh Quan Nguyen, Do Hyung Kim, Hye Ji Shim, Huynh Kim Khanh Ta, Thi Luong Vu, Thi Kieu Oanh Nguyen, Jung Chae Lim, Han Choe

{"title":"Novel Anti-Mesothelin Nanobodies and Recombinant Immunotoxins with Pseudomonas Exotoxin Catalytic Domain for Cancer Therapeutics.","authors":"Minh Quan Nguyen, Do Hyung Kim, Hye Ji Shim, Huynh Kim Khanh Ta, Thi Luong Vu, Thi Kieu Oanh Nguyen, Jung Chae Lim, Han Choe","doi":"10.14348/molcells.2023.0155","DOIUrl":"10.14348/molcells.2023.0155","url":null,"abstract":"Recombinant immunotoxins (RITs) are fusion proteins consisting of a targeting domain linked to a toxin, offering a highly specific therapeutic strategy for cancer treatment. In this study, we engineered and characterized RITs aimed at mesothelin, a cell surface glycoprotein overexpressed in various malignancies. Through an extensive screening of a large nanobody library, four mesothelin-specific nanobodies were selected and genetically fused to a truncated Pseudomonas exotoxin (PE24B). Various optimizations, including the incorporation of furin cleavage sites, maltose-binding protein tags, and tobacco etch virus protease cleavage sites, were implemented to improve protein expression, solubility, and purification. The RITs were successfully overexpressed in Escherichia coli, achieving high solubility and purity post-purification. In vitro cytotoxicity assays on gastric carcinoma cell lines NCI-N87 and AGS revealed that Meso(Nb2)-PE24B demonstrated the highest cytotoxic efficacy, warranting further characterization. This RIT also displayed selective binding to human and monkey mesothelins but not to mouse mesothelin. The competitive binding assays between different RIT constructs revealed significant alterations in IC50 values, emphasizing the importance of nanobody specificity. Finally, a modification in the endoplasmic reticulum retention signal at the C-terminus further augmented its cytotoxic activity. Our findings offer valuable insights into the design and optimization of RITs, showcasing the potential of Meso(Nb2)-PE24B as a promising therapeutic candidate for targeted cancer treatment.","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10701305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Transcription Factor EB-Mediated Lysosomal Function Regulation for Determining Stem Cell Fate under Metabolic Stress. 转录因子 EB 介导的溶酶体功能调节决定代谢压力下的干细胞命运

IF 3.8 3区生物学

Molecules and Cells Pub Date : 2023-12-31 Epub Date: 2023-12-04 DOI: 10.14348/molcells.2023.0143

Chang Woo Chae, Young Hyun Jung, Ho Jae Han

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Deup1 Expression Interferes with Multiciliated Differentiation. Deup1的表达会干扰多纤毛分化

IF 3.8 3区生物学

Molecules and Cells Pub Date : 2023-12-31 Epub Date: 2023-11-08 DOI: 10.14348/molcells.2023.0149

Miram Shin, Jiyeon Lee, Haeryung Lee, Vijay Kumar, Jaebong Kim, Soochul Park

{"title":"Deup1 Expression Interferes with Multiciliated Differentiation.","authors":"Miram Shin, Jiyeon Lee, Haeryung Lee, Vijay Kumar, Jaebong Kim, Soochul Park","doi":"10.14348/molcells.2023.0149","DOIUrl":"10.14348/molcells.2023.0149","url":null,"abstract":"A recent study revealed that the loss of Deup1 expression does not affect either centriole amplification or multicilia formation. Therefore, the deuterosome per se is not a platform for amplification of centrioles. In this study, we examine whether gain-of-function of Deup1 affects the development of multiciliated ependymal cells. Our time-lapse study reveals that deuterosomes with an average diameter of 300 nm have two different fates during ependymal differentiation. In the first instance, deuterosomes are scattered and gradually disappear as cells become multiciliated. In the second instance, deuterosomes self-organize into a larger aggregate, called a deuterosome cluster (DC). Unlike scattered deuterosomes, DCs possess centriole components primarily within their large structure. A characteristic of DC-containing cells is that they tend to become primary ciliated rather than multiciliated. Our in utero electroporation study shows that DCs in ependymal tissue are mostly observed at early postnatal stages, but are scarce at late postnatal stages, suggesting the presence of DC antagonists within the differentiating cells. Importantly, from our bead flow assay, ectopic expression of Deup1 significantly impairs cerebrospinal fluid flow. Furthermore, we show that expression of mouse Deup1 in Xenopus embryos has an inhibitory effect on differentiation of multiciliated cells in the epidermis. Taken together, we conclude that the DC formation of Deup1 in multiciliated cells inhibits production of multiple centrioles.","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10701303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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ANKS1A-Deficiency Aberrantly Increases the Entry of the Protein Transport Machinery into the Ependymal Cilia. ANKS1A缺陷会异常增加蛋白质运输机械进入外膜纤毛的机会

IF 3.8 3区生物学

Molecules and Cells Pub Date : 2023-12-31 Epub Date: 2023-11-28 DOI: 10.14348/molcells.2023.0153

Haeryung Lee, Jiyeon Lee, Miram Shin, Soochul Park

{"title":"ANKS1A-Deficiency Aberrantly Increases the Entry of the Protein Transport Machinery into the Ependymal Cilia.","authors":"Haeryung Lee, Jiyeon Lee, Miram Shin, Soochul Park","doi":"10.14348/molcells.2023.0153","DOIUrl":"10.14348/molcells.2023.0153","url":null,"abstract":"In this study, we examine whether a change in the protein levels for FOP in Ankyrin repeat and SAM domain-containing protein 1A (ANKS1A)-deficient ependymal cells affects the intraflagellar transport (IFT) protein transport system in the multicilia. Three distinct abnormalities are observed in the multicilia of ANKS1A-deficient ependymal cells. First, there were a greater number of IFT88-positive trains along the cilia from ANKS1A deficiency. The results are similar to each isolated cilium as well. Second, each isolated cilium contains a significant increase in the number of extracellular vesicles (ECVs) due to the lack of ANKS1A. Third, Van Gogh-like 2 (Vangl2), a ciliary membrane protein, is abundantly detected along the cilia and in the ECVs attached to them for ANKS1A-deficient cells. We also use primary ependymal culture systems to obtain the ECVs released from the multicilia. Consequently, we find that ECVs from ANKS1A-deficient cells contain more IFT machinery and Vangl2. These results indicate that ANKS1A deficiency increases the entry of the protein transport machinery into the multicilia and as a result of these abnormal protein transports, excessive ECVs form along the cilia. We conclude that ependymal cells make use of the ECV-based disposal system in order to eliminate excessively transported proteins from basal bodies.","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10701301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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