Molecular and Cellular Biology最新文献_第6页

LncRNA AA465934 Improves Podocyte Injury by Promoting Tristetraprolin-Mediated HMGB1 DownRegulation in Diabetic Nephropathy. LncRNA AA465934通过促进Tristetraprolin介导的HMGB1下调改善糖尿病肾病的荚膜细胞损伤

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-03-23 DOI: 10.1080/10985549.2024.2325527

Nan Yang, Yue Zhang, Peiyao Ren, Li Zhao, Danna Zheng, Lanjun Fu, Juan Jin

{"title":"LncRNA AA465934 Improves Podocyte Injury by Promoting Tristetraprolin-Mediated HMGB1 DownRegulation in Diabetic Nephropathy.","authors":"Nan Yang, Yue Zhang, Peiyao Ren, Li Zhao, Danna Zheng, Lanjun Fu, Juan Jin","doi":"10.1080/10985549.2024.2325527","DOIUrl":"10.1080/10985549.2024.2325527","url":null,"abstract":"Although LncRNA AA465934 expression is reduced in high glucose (HG)-treated podocytes, its role in HG-mediated podocyte injury and diabetic nephropathy (DN) remains unknown. Herein, we investigated the role of AA465934 in HG-mediated podocyte injury and DN using a spontaneous type II diabetic nephropathy (T2DN) model. The model was created by injecting AA465934 overexpressed adeno-associated virus (AAV) or control into mice. The levels of renal function, proteinuria, renal structural lesions, and podocyte apoptosis were then examined. Furthermore, AA465934 and autophagy levels, as well as tristetraprolin (TTP) and high mobility group box 1 (HMGB1) expression changes were detected. We also observed podocyte injury and the binding ability of TTP to E3 ligase proviral insertion in murine lymphomas 2 (PIM2), AA465934, or HMGB1. According to the results, AA465934 improved DN progression and podocyte damage in T2DN mice. In addition, AA465934 bound to TTP and inhibited its degradation by blocking TTP-PIM2 binding. Notably, TTP knock-down blocked the ameliorating effects of AA465934 and TTP bound HMGB1 mRNA, reducing its expression. Overexpression of HMGB1 inhibited the ability of AA465934 and TTP to improve podocyte injury. Furthermore, AA465934 bound TTP, inhibiting TTP-PIM2 binding, thereby suppressing TTP degradation, downregulating HMGB1, and reversing autophagy downregulation, ultimately alleviating HG-mediated podocyte injury and DN. Based on these findings, we deduced that the AA465934/TTP/HMGB1/autophagy axis could be a therapeutic avenue for managing podocyte injury and DN.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"87-102"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10986766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194168","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}

引用次数: 0

SPRING is a Dedicated Licensing Factor for SREBP-Specific Activation by S1P. SPRING 是 S1P 激活 SREBP 的专用许可因子。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-05-15 DOI: 10.1080/10985549.2024.2348711

Sebastian Hendrix, Josephine M E Tan, Klevis Ndoj, Jenina Kingma, Masoud Valiloo, Lobke F Zijlstra, Roelof Ottenhoff, Nabil G Seidah, Anke Loregger, Daniel L Kober, Noam Zelcer

{"title":"SPRING is a Dedicated Licensing Factor for SREBP-Specific Activation by S1P.","authors":"Sebastian Hendrix, Josephine M E Tan, Klevis Ndoj, Jenina Kingma, Masoud Valiloo, Lobke F Zijlstra, Roelof Ottenhoff, Nabil G Seidah, Anke Loregger, Daniel L Kober, Noam Zelcer","doi":"10.1080/10985549.2024.2348711","DOIUrl":"10.1080/10985549.2024.2348711","url":null,"abstract":"SREBP transcription factors are central regulators of lipid metabolism. Their proteolytic activation requires ER to the Golgi translocation and subsequent cleavage by site-1-protease (S1P). Produced as a proprotein, S1P undergoes autocatalytic cleavage from its precursor S1PA to mature S1PC form. Here, we report that SPRING (previously C12ORF29) and S1P interact through their ectodomains, and that this facilitates the autocatalytic cleavage of S1PA into its mature S1PC form. Reciprocally, we identified a S1P recognition-motif in SPRING and demonstrate that S1P-mediated cleavage leads to secretion of the SPRING ectodomain in cells, and in liver-specific Spring knockout (LKO) mice transduced with AAV-mSpring. By reconstituting SPRING variants into SPRINGKO cells we show that the SPRING ectodomain supports proteolytic maturation of S1P and SREBP signaling, but that S1P-mediated SPRING cleavage is not essential for these processes. Absence of SPRING modestly diminishes proteolytic maturation of S1PA→C and trafficking of S1PC to the Golgi. However, despite reaching the Golgi in SPRINGKO cells, S1PC fails to rescue SREBP signaling. Remarkably, whereas SREBP signaling was severely attenuated in SPRINGKO cells and LKO mice, that of ATF6, another S1P substrate, was unaffected in these models. Collectively, our study positions SPRING as a dedicated licensing factor for SREBP-specific activation by S1P.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"123-137"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11110692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922665","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}

引用次数: 0

Deactivation of the Unfolded Protein Response Aggravated Renal AA Amyloidosis in HSF1 Deficiency Mice. 解除折叠蛋白反应会加重 HSF1 缺乏小鼠的肾 AA 淀粉样变性。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-05-17 DOI: 10.1080/10985549.2024.2347937

Wei Liu, Shunjie Xia, Fang Yao, Jia Huo, Junqiao Qian, Xiaomeng Liu, Langning Bai, Yu Song, Jinze Qian

{"title":"Deactivation of the Unfolded Protein Response Aggravated Renal AA Amyloidosis in HSF1 Deficiency Mice.","authors":"Wei Liu, Shunjie Xia, Fang Yao, Jia Huo, Junqiao Qian, Xiaomeng Liu, Langning Bai, Yu Song, Jinze Qian","doi":"10.1080/10985549.2024.2347937","DOIUrl":"10.1080/10985549.2024.2347937","url":null,"abstract":"Systemic amyloid A (AA) amyloidosis, which is considered the second most common form of systemic amyloidosis usually takes place several years prior to the occurrence of chronic inflammation, generally involving the kidney. Activated HSF1, which alleviated unfolded protein response (UPR) or enhanced HSR, is the potential therapeutic target of many diseases. However, the effect of HSF1 on AA amyloidosis remains unclear. This study focused on evaluating effect of HSF1 on AA amyloidosis based on HSF1 knockout mice. As a result, aggravated amyloid deposits and renal dysfunction have been found in HSF1 knockout mice. In progressive AA amyloidosis, HSF1 deficiency enhances serum amyloid A production might to lead to severe AA amyloid deposition in mice, which may be related to deactivated unfolded protein response as well as enhanced inflammation. Thus, HSF1 plays a significant role on UPR related pathway impacting AA amyloid deposition, which can mitigate amyloidogenic proteins from aggregation pathologically and is the possible way for intervening with the pathology of systemic amyloid disorder. In conclusion, HSF1 could not only serve as a new target for AA amyloidosis treatment in the future, but HSF1 knockout mice also can be considered as a valuable novel animal model for renal AA amyloidosis.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"165-177"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11123510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958492","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}

引用次数: 0

TCF12 Transcriptionally Activates SPHK1 to Induce Osteosarcoma Angiogenesis by Promoting the S1P/S1PR4/STAT3 Axis. TCF12 通过促进 S1P/S1PR4/STAT3 轴转录激活 SPHK1 以诱导骨肉瘤血管生成

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-05-20 DOI: 10.1080/10985549.2024.2341781

Wo Li, Jitong Liu, Ting Cai, Xia Hu

{"title":"TCF12 Transcriptionally Activates SPHK1 to Induce Osteosarcoma Angiogenesis by Promoting the S1P/S1PR4/STAT3 Axis.","authors":"Wo Li, Jitong Liu, Ting Cai, Xia Hu","doi":"10.1080/10985549.2024.2341781","DOIUrl":"10.1080/10985549.2024.2341781","url":null,"abstract":"Transcription factor 12 (TCF12) is a known oncogene in many cancers. However, whether TCF12 can regulate malignant phenotypes and angiogenesis in osteosarcoma is not elucidated. In this study, we demonstrated increased expression of TCF12 in osteosarcoma tissues and cell lines. High TCF12 expression was associated with metastasis and poor survival rate of osteosarcoma patients. Knockdown of TCF12 reduced the proliferation, migration, and invasion of osteosarcoma cells. TCF12 was found to bind to the promoter region of sphingosine kinase 1 (SPHK1) to induce transcriptional activation of SPHK1 expression and enhance the secretion of sphingosine-1-phosphate (S1P), which eventually resulted in the malignant phenotypes of osteosarcoma cells. In addition, S1P secreted by osteosarcoma cells promoted the angiogenesis of HUVECs by targeting S1PR4 on the cell membrane to activate the STAT3 signaling pathway. These findings suggest that TCF12 may induce transcriptional activation of SPHK1 to promote the synthesis and secretion of S1P. This process likely enhances the malignant phenotypes of osteosarcoma cells and induces angiogenesis via the S1PR4/STAT3 signaling pathway.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"178-193"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11123469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065035","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}

引用次数: 0

Increased ANKRD1 Levels in Early Senescence Mediated by RBMS1-Elicited ANKRD1 mRNA Stabilization. 由 RBMS1 引起的 ANKRD1 mRNA 稳定介导的早期衰老中 ANKRD1 水平的增加

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-05-20 DOI: 10.1080/10985549.2024.2350540

Chang Hoon Shin, Martina Rossi, Carlos Anerillas, Jennifer L Martindale, Xiaoling Yang, Eunbyul Ji, Apala Pal, Rachel Munk, Jen-Hao Yang, Dimitrios Tsitsipatis, Krystyna Mazan-Mamczarz, Kotb Abdelmohsen, Myriam Gorospe

{"title":"Increased ANKRD1 Levels in Early Senescence Mediated by RBMS1-Elicited ANKRD1 mRNA Stabilization.","authors":"Chang Hoon Shin, Martina Rossi, Carlos Anerillas, Jennifer L Martindale, Xiaoling Yang, Eunbyul Ji, Apala Pal, Rachel Munk, Jen-Hao Yang, Dimitrios Tsitsipatis, Krystyna Mazan-Mamczarz, Kotb Abdelmohsen, Myriam Gorospe","doi":"10.1080/10985549.2024.2350540","DOIUrl":"10.1080/10985549.2024.2350540","url":null,"abstract":"Cellular senescence is a dynamic biological process triggered by sublethal cell damage and driven by specific changes in gene expression programs. We recently identified ANKRD1 (ankyrin repeat domain 1) as a protein strongly elevated after triggering senescence in fibroblasts. Here, we set out to investigate the mechanisms driving the elevated production of ANKRD1 in the early stages of senescence. Our results indicated that the rise in ANKRD1 levels after triggering senescence using etoposide (Eto) was the result of moderate increases in transcription and translation, and robust mRNA stabilization. Antisense oligomer (ASO) pulldown followed by mass spectrometry revealed a specific interaction of the RNA-binding protein RBMS1 with ANKRD1 mRNA that was confirmed by ribonucleoprotein immunoprecipitation analysis. RBMS1 abundance decreased in the nucleus and increased in the cytoplasm during Eto-induced senescence; in agreement with the hypothesis that RBMS1 may participate in post-transcriptional stabilization of ANKRD1 mRNA, silencing RBMS1 reduced, while overexpressing RBMS1 enhanced ANKRD1 mRNA half-life after Eto treatment. A segment proximal to the ANKRD1 coding region was identified as binding RBMS1 and conferring RBMS1-dependent increased expression of a heterologous reporter. We propose that RBMS1 increases expression of ANKRD1 during the early stages of senescence by stabilizing ANKRD1 mRNA.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"194-208"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11123458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071373","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}

引用次数: 0

Statement of Retraction: Molecular Dissection of Interactions between Rad51 and Members of the Recombination-Repair. 撤回声明：Rad51 与重组-配对（Recombination-Repair.

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-06-06 DOI: 10.1080/10985549.2024.2358694

引用次数: 0

Regulation of PPARγ2 Stability and Activity by SHP-1. SHP-1 对 PPARγ2 稳定性和活性的调控

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-06-03 DOI: 10.1080/10985549.2024.2354959

Amit Kumar, Beisy Laborit Labrada, Marie-Hélène Lavallée-Bourget, Marie-Pier Forest, Michael Schwab, Kerstin Bellmann, Vanessa Houde, Nicole Beauchemin, Mathieu Laplante, André Marette

{"title":"Regulation of PPARγ2 Stability and Activity by SHP-1.","authors":"Amit Kumar, Beisy Laborit Labrada, Marie-Hélène Lavallée-Bourget, Marie-Pier Forest, Michael Schwab, Kerstin Bellmann, Vanessa Houde, Nicole Beauchemin, Mathieu Laplante, André Marette","doi":"10.1080/10985549.2024.2354959","DOIUrl":"10.1080/10985549.2024.2354959","url":null,"abstract":"The protein tyrosine phosphatase Src homology region 2 domain-containing phosphatase-1 (SHP-1) plays an important role in modulating glucose and lipid homeostasis. We previously suggested a potential role of SHP-1 in the regulation of peroxisome proliferator-activated receptor γ2 (PPARγ2) expression and activity but the mechanisms were unexplored. PPARγ2 is the master regulator of adipogenesis, but how its activity is regulated by tyrosine phosphorylation is largely unknown. Here, we found that SHP-1 binds to PPARγ2 primarily via its N-terminal SH2-domain. We confirmed the phosphorylation of PPARγ2 on tyrosine-residue 78 (Y78), which was reduced by SHP-1 in vitro resulting in decreased PPARγ2 stability. Loss of SHP-1 led to elevated, agonist-induced expression of the classical PPARγ2 targets FABP4 and CD36, concomitant with increased lipid content in cells expressing PPARγ2, an effect blunted by abrogation of PPARγ2 phosphorylation. Collectively, we discovered that SHP-1 affects the stability of PPARγ2 through dephosphorylation thereby influencing adipogenesis.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"261-272"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200299","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}

引用次数: 0

ELF5-Regulated lncRNA-TTN-AS1 Alleviates Myocardial Cell Injury via Recruiting PCBP2 to Increase CDK6 Stability in Myocardial Infarction. ELF5调控的lncRNA-TTN-AS1通过招募PCBP2增加心肌梗死中CDK6的稳定性减轻心肌细胞损伤

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-07-21 DOI: 10.1080/10985549.2024.2374083

Yonglin Zhang, Zhenglu Shang, Shucan Xu, Guangzhi Zhou, Aijun Liu

{"title":"ELF5-Regulated lncRNA-TTN-AS1 Alleviates Myocardial Cell Injury via Recruiting PCBP2 to Increase CDK6 Stability in Myocardial Infarction.","authors":"Yonglin Zhang, Zhenglu Shang, Shucan Xu, Guangzhi Zhou, Aijun Liu","doi":"10.1080/10985549.2024.2374083","DOIUrl":"10.1080/10985549.2024.2374083","url":null,"abstract":"Myocardial infarction (MI) seriously threatens the health of elderly people, and reducing myocardial injury is of great significance for the treatment of MI. LncRNA-TTN-AS1 shows protective effects on cardiomyocyte injury, while the role of TTN-AS1 in MI remains unknown. CCK8, flow cytometry, and JC-1 staining assessed cell viability, apoptosis and mitochondrial membrane potential (MMP), respectively. Cellular reactive oxygen species (ROS) and secreted lactate dehydrogenase (LDH) levels were measured. The interactions between ELF5, TTN-AS1, PCBP2 and CDK6 were explored using ChIP, luciferase reporter assay, RIP, and pull-down. The severity of MI in mice was evaluated using TTC, H&E, and TUNEL staining. The data revealed that OGD/R significantly induced ROS, mitochondrial injury and apoptosis in AC16 cells, while overexpression of ELF5 or TTN-AS1 reversed these phenomena. ELF5 transcriptionally activated TTN-AS1 through binding with its promoter. TTN-AS1 increased CDK6 stability via recruiting PCBP2. CDK6 knockdown abolished the inhibitory effects of TTN-AS1 overexpression on OGD/R-induced myocardial injury. Furthermore, overexpression of TTN-AS1 or ELF5 alleviated MI progression in mice by upregulating CDK6. Collectively, TTN-AS1 transcriptionally regulated by ELF5 alleviated myocardial apoptosis and injury during MI via recruiting PCBP2 to increase CDK6 stability, which shed new lights on exploring new strategies against MI.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"303-315"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11296528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734606","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}

引用次数: 0

Phosphorylation of Orc6 During Mitosis Regulates DNA Replication and Ribosome Biogenesis. 有丝分裂过程中 Orc6 的磷酸化调控 DNA 复制和核糖体生物发生

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-06-12 DOI: 10.1080/10985549.2024.2356880

Fredy Kurniawan, Arindam Chakraborty, Humayra Z Oishi, Minxue Liu, Mariam K Arif, David Chen, Rishabh Prasanth, Yo-Chuen Lin, Godwin Olalaye, Kannanganattu V Prasanth, Supriya G Prasanth

{"title":"Phosphorylation of Orc6 During Mitosis Regulates DNA Replication and Ribosome Biogenesis.","authors":"Fredy Kurniawan, Arindam Chakraborty, Humayra Z Oishi, Minxue Liu, Mariam K Arif, David Chen, Rishabh Prasanth, Yo-Chuen Lin, Godwin Olalaye, Kannanganattu V Prasanth, Supriya G Prasanth","doi":"10.1080/10985549.2024.2356880","DOIUrl":"10.1080/10985549.2024.2356880","url":null,"abstract":"The human Origin Recognition Complex (ORC) is required not only for the initiation of DNA replication, but is also implicated in diverse cellular functions, including chromatin organization, centrosome biology, and cytokinesis. The smallest subunit of ORC, Orc6, is poorly conserved amongst eukaryotes. Recent studies from our laboratory have suggested that human Orc6 is not required for replication licensing, but is needed for S-phase progression. Further, ATR-dependent phosphorylation of Orc6 at T229 is implicated in DNA damage response during S-phase. In this study, we demonstrate that the CDK-dependent phosphorylation of Orc6 at T195 occurs during mitosis. While the phosphorylation at T195 does not seem to be required to exit mitosis, cells expressing the phosphomimetic T195E mutant of Orc6 impede S-phase progression. Moreover, the phosphorylated form of Orc6 associates with ORC more robustly, and Orc6 shows enhanced association with the ORC outside of G1, supporting the view that Orc6 may prevent the role of Orc1-5 in licensing outside of G1. Finally, Orc6 and the phosphorylated Orc6 localize to the nucleolar organizing centers and regulate ribosome biogenesis. Our results suggest that phosphorylated Orc6 at T195 prevents replication.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"289-301"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311045","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}

引用次数: 0

Reconstitution of Rab11-FIP4 Expression Rescues Cellular Homeostasis in Cystinosis. 重建 Rab11-FIP4 表达可恢复胱氨酸沉积症的细胞稳态

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-10-22 DOI: 10.1080/10985549.2024.2410814

Farhana Rahman, Jennifer L Johnson, Mouad Ait Kbaich, Elsa Meneses-Salas, Aparna Shukla, Danni Chen, William B Kiosses, Evripidis Gavathiotis, Ana Maria Cuervo, Stephanie Cherqui, Sergio D Catz

{"title":"Reconstitution of Rab11-FIP4 Expression Rescues Cellular Homeostasis in Cystinosis.","authors":"Farhana Rahman, Jennifer L Johnson, Mouad Ait Kbaich, Elsa Meneses-Salas, Aparna Shukla, Danni Chen, William B Kiosses, Evripidis Gavathiotis, Ana Maria Cuervo, Stephanie Cherqui, Sergio D Catz","doi":"10.1080/10985549.2024.2410814","DOIUrl":"10.1080/10985549.2024.2410814","url":null,"abstract":"Rab11 family interacting protein 4 (Rab11-FIP4) regulates endocytic trafficking. A possible role for Rab11-FIP4 in the regulation of lysosomal function has been proposed, but its precise function in the regulation of cellular homeostasis is unknown. By mRNA array and protein analysis, we found that Rab11-FIP4 is downregulated in the lysosomal storage disease cystinosis, which is caused by genetic defects in the lysosomal cystine transporter, cystinosin. Rescue of Rab11-FIP4 expression in Ctns-/- fibroblasts re-established normal autophagosome levels and decreased LC3B-II expression in cystinotic cells. Furthermore, Rab11-FIP4 reconstitution increased the localization of the chaperone-mediated autophagy receptor LAMP2A at the lysosomal membrane. Treatment with genistein, a phytoestrogen that upregulates macroautophagy, or the CMA activator QX77 (CA77) restored Rab11-FIP4 expression levels in cystinotic cells supporting a cross-regulation between two independent autophagic mechanisms, lysosomal function and Rab11-FIP4. Improved cellular homeostasis in cystinotic cells rescued by Rab11-FIP4 expression correlated with decreased endoplasmic reticulum stress, an effect that was potentiated by Rab11 and partially blocked by expression of a dominant negative Rab11. Restoring Rab11-FIP4 expression in cystinotic proximal tubule cells increased the localization of the endocytic receptor megalin at the plasma membrane, suggesting that Rab11-FIP4 reconstitution has the potential to improve cellular homeostasis and function in cystinosis.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"577-589"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470010","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}

引用次数: 0