Sadhana R N Sudhakar, Shahper N Khan, Ariel Clark, Thordur Hendrickson-Rebizant, Shrinal Patel, Ted M Lakowski, James R Davie
{"title":"Protein arginine methyltransferase 1, a major regulator of biological processes.","authors":"Sadhana R N Sudhakar, Shahper N Khan, Ariel Clark, Thordur Hendrickson-Rebizant, Shrinal Patel, Ted M Lakowski, James R Davie","doi":"10.1139/bcb-2023-0212","DOIUrl":"10.1139/bcb-2023-0212","url":null,"abstract":"<p><p>Protein arginine methyltransferase 1 (PRMT1) is a major type I arginine methyltransferase that catalyzes the formation of monomethyl and asymmetric dimethylarginine in protein substrates. It was first identified to asymmetrically methylate histone H4 at the third arginine residue forming the H4R3me2a active histone mark. However, several protein substrates are now identified as being methylated by PRMT1. As a result of its association with diverse classes of substrates, PRMT1 regulates several biological processes like chromatin dynamics, transcription, RNA processing, and signal transduction. The review provides an overview of PRMT1 structure, biochemical features, specificity, regulation, and role in cellular functions. We discuss the genomic distribution of PRMT1 and its association with <i>tRNA</i> genes. Further, we explore the different substrates of PRMT1 involved in splicing. In the end, we discuss the proteins that interact with PRMT1 and their downstream effects in diseased states.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"106-126"},"PeriodicalIF":2.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71433869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Naeem Ullah, Javed Ali Khan, Sultan Almakdi, Mohammed S Alshehri, Mimonah Al Qathrady, Muhammad Shahid Anwar, Ikram Syed
{"title":"ChestCovidNet: An Effective DL-based Approach for COVID-19, Lung Opacity, and Pneumonia Detection Using Chest Radiographs Images.","authors":"Naeem Ullah, Javed Ali Khan, Sultan Almakdi, Mohammed S Alshehri, Mimonah Al Qathrady, Muhammad Shahid Anwar, Ikram Syed","doi":"10.1139/bcb-2023-0265","DOIUrl":"https://doi.org/10.1139/bcb-2023-0265","url":null,"abstract":"<p><p>Currently used lung disease screening tools are expensive in terms of money and time. Therefore, chest radiograph images (CRIs) are employed for prompt and accurate COVID-19 identification. Recently, many researchers have applied Deep learning (DL) based models to detect COVID-19 automatically. However, their model could have been more computationally expensive and less robust, i.e., its performance degrades when evaluated on other datasets. This study proposes a trustworthy, robust, and lightweight network (ChestCovidNet) that can detect COVID-19 by examining various CRIs datasets. The ChestCovidNet model has only 11 learned layers, eight convolutional (Conv) layers, and three fully connected (FC) layers. The framework employs both the Conv and group Conv layers, Leaky Relu activation function, shufflenet unit, Conv kernels of 3×3 and 1×1 to extract features at different scales, and two normalization procedures that are cross-channel normalization and batch normalization. We used 9013 CRIs for training whereas 3863 CRIs for testing the proposed ChestCovidNet approach. Furthermore, we compared the classification results of the proposed framework with hybrid methods in which we employed DL frameworks for feature extraction and support vector machines (SVM) for classification. The study's findings demonstrated that the embedded low-power ChestCovidNet model worked well and achieved a classification accuracy of 98.12% and recall, F1-score, and precision of 95.75%.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nour-El-Houda Hammami, Natacha Mérindol, Mélodie B Plourde, Tara Maisonnet, Sophie Lebel, Lionel Berthoux
{"title":"SUMO-3 promotes the ubiquitin-dependent turnover of TRIM55.","authors":"Nour-El-Houda Hammami, Natacha Mérindol, Mélodie B Plourde, Tara Maisonnet, Sophie Lebel, Lionel Berthoux","doi":"10.1139/bcb-2023-0153","DOIUrl":"10.1139/bcb-2023-0153","url":null,"abstract":"<p><p>Human muscle-specific RING fingers (MURFs) are members of the tripartite motif (TRIM) family of proteins characterized by their C-terminal subgroup one signature domain. MURFs play a role in sarcomere formation and microtubule dynamics. It was previously established that some TRIMs undergo post-translational modification by small ubiquitin-like modifier (SUMO). In this study, we explored the putative SUMOylation of MURF proteins as well as their interactions with SUMO. MURF proteins (TRIM54, TRIM55, and TRIM63) were not found to be SUMOylated. However, TRIM55 turnover by proteasomal and lysosomal degradation was higher upon overexpression of SUMO-3 but not of SUMO-1. Furthermore, it is predicted that TRIM55 contains two potential SUMO-interacting motifs (SIMs). We found that SIM1- and SIM2-mutated TRIM55 were more stable than the wild-type (WT) protein partly due to decreased degradation. Consistently, SIM-mutated TRIM55 was less polyubiquitinated than the WT protein, despite similar monoubiquitination levels. Using IF microscopy, we observed that SIM motifs influenced TRIM55 subcellular localization. In conclusion, our results suggest that SUMO-3 or SUMO-3-modified proteins modulate the localization, stability, and RING ubiquitin ligase activity of TRIM55.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"73-84"},"PeriodicalIF":2.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10228876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bin Zhang, Ruowen Sun, Min Gu, Zehui Jiang, Ye Wang, Linlin Zhang, Xiaoyang Liu, Zuofei Chi
{"title":"RNA-binding protein NOVA1 promotes acute T-lymphocyte leukemia progression by stabilizing USP44 mRNA.","authors":"Bin Zhang, Ruowen Sun, Min Gu, Zehui Jiang, Ye Wang, Linlin Zhang, Xiaoyang Liu, Zuofei Chi","doi":"10.1139/bcb-2023-0092","DOIUrl":"10.1139/bcb-2023-0092","url":null,"abstract":"<p><p>Acute T-lymphocyte leukemia (T-ALL) is a malignant tumor disease. RNA-binding protein neotumor ventral antigen-1 (NOVA1) is highly expressed in bone marrow mononuclear cells of T-ALL patients, while the role of NOVA1 in T-ALL progression remains unknown. The gain- and loss-of-function studies for NOVA1 were performed in Jurkat and CCRF-CEM cells. NOVA1 overexpression promoted cell proliferation and cell cycle progression. NOVA1 knockdown increased the apoptosis rate of T-ALL cells. Ubiquitin-specific protease 44 (USP44), a nuclear protein with deubiquitinase catalytic activity, has been reported to play an oncogene role in human T-cell leukemia. USP44 expression was positively associated with NOVA1, and RNA immunoprecipitation assay verified the binding of NOVA1 to the mRNA of USP44. USP44 knockdown partially abolished NOVA1-induced cell proliferation and inhibition of apoptosis. The in vivo xenograft experiment was performed by injection of T-ALL tumor cells into the tail vein of NOD/SCID mice. The knockdown of NOVA1 had lower tumorigenicity. NOVA1 knockdown alleviated pathological changes in lung and spleen tissues, and increased the overall survival period and the weight of T-ALL mice. Thus, NOVA1 acts as an accelerator in T-ALL, and its function might be achieved by binding to and stabilizing USP44 mRNA.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"60-72"},"PeriodicalIF":2.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41189736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dannielle L Gemmill, Corey R Nelson, Maulik D Badmalia, Higor S Pereira, Liam Kerr, Michael T Wolfinger, Trushar R Patel
{"title":"The 3' terminal region of Zika virus RNA contains a conserved G-quadruplex and is unfolded by human DDX17.","authors":"Dannielle L Gemmill, Corey R Nelson, Maulik D Badmalia, Higor S Pereira, Liam Kerr, Michael T Wolfinger, Trushar R Patel","doi":"10.1139/bcb-2023-0036","DOIUrl":"10.1139/bcb-2023-0036","url":null,"abstract":"<p><p>Zika virus (ZIKV) infection remains a worldwide concern, and currently no effective treatments or vaccines are available. Novel therapeutics are an avenue of interest that could probe viral RNA-human protein communication to stop viral replication. One specific RNA structure, G-quadruplexes (G4s), possess various roles in viruses and all domains of life, including transcription and translation regulation and genome stability, and serves as nucleation points for RNA liquid-liquid phase separation. Previous G4 studies on ZIKV using a quadruplex forming G-rich sequences Mapper located a potential G-quadruplex sequence in the 3' terminal region (TR) and was validated structurally using a 25-mer oligo. It is currently unknown if this structure is conserved and maintained in a large ZIKV RNA transcript and its specific roles in viral replication. Using bioinformatic analysis and biochemical assays, we demonstrate that the ZIKV 3' TR G4 is conserved across all ZIKV isolates and maintains its structure in a 3' TR full-length transcript. We further established the G4 formation using pyridostatin and the BG4 G4-recognizing antibody binding assays. Our study also demonstrates that the human DEAD-box helicases, DDX3X<sub>132-607</sub> and DDX17<sub>135-555</sub>, bind to the 3' TR and that DDX17<sub>135-555</sub> unfolds the G4 present in the 3' TR. These findings provide a path forward in potential therapeutic targeting of DDX3X or DDX17's binding to the 3' TR G4 region for novel treatments against ZIKV.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"96-105"},"PeriodicalIF":2.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41106050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"LncRNAs: the good, the bad, and the unknown.","authors":"Ganesan Arunkumar","doi":"10.1139/bcb-2023-0155","DOIUrl":"10.1139/bcb-2023-0155","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) are significant contributors in maintaining genomic integrity through epigenetic regulation. LncRNAs can interact with chromatin-modifying complexes in both <i>cis</i> and <i>trans</i> pathways, drawing them to specific genomic loci and influencing gene expression via DNA methylation, histone modifications, and chromatin remodeling. They can also operate as building blocks to assemble different chromatin-modifying components, facilitating their interactions and gene regulatory functions. Deregulation of these molecules has been associated with various human diseases, including cancer, cardiovascular disease, and neurological disorders. Thus, lncRNAs are implicated as potential diagnostic indicators and therapeutic targets. This review discusses the current understanding of how lncRNAs mediate epigenetic control, genomic integrity, and their putative functions in disease pathogenesis.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"9-27"},"PeriodicalIF":2.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10353141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Note of appreciation.","authors":"","doi":"10.1139/bcb-2023-0272","DOIUrl":"10.1139/bcb-2023-0272","url":null,"abstract":"","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":"102 1","pages":"i"},"PeriodicalIF":2.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"WWP2 binds to NKRF, enhances the NF-κB signaling, and promotes malignant phenotypes of acute myeloid leukemia cells.","authors":"Hongjia Wang, Xin Lian, Kexin Wang, Shuye Wang","doi":"10.1139/bcb-2022-0360","DOIUrl":"10.1139/bcb-2022-0360","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is one of the hematological malignancies with a high recurrence rate. WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) is identified as a pivotal regulator of tumor progression. This study aimed to assess the possible role of WWP2 in AML. Analysis of the GEPIA database indicated an elevated WWP2 expression in AML. We established stable WWP2-overexpressed or WWP2-silenced cells using lentivirus loaded with cDNA encoding WWP2 mRNA or shRNA targeting WWP2. Notably, WWP2 overexpression facilitated cell proliferation and cell cycle progression, which was manifested as the increase of colony formation number, S-phase percentage and cell cycle related protein levels. As observed, WWP2 knockdown presented opposite effects, leading to inhibition of tumorigenicity. Strikingly, WWP2 knockdown induced apoptosis, accompanied by upregulation of pro-apoptosis proteins cleaved caspase-9, Bax and cleaved caspase-3 and downregulation of anti-apoptosis protein Bcl-2. Functionally, we further confirmed that WWP2 overexpression enhanced the NF-κB signaling and upregulated the levels of downstream genes, which may contribute to aggravating the development of AML. More importantly, by co-immunoprecipitation assay, we verified that WWP2 bound to NF-κB-repressing factor (NKRF) and promoted NKRF ubiquitylation. Dramatically, NKRF overexpression abolished the role of WWP2 in facilitating the process of AML. Overall, our observations confirm that WWP2 exerts a critical role in the tumorigenicity of AML, and NKRF is regarded as an essential factor in the WWP2-mediated AML progression. WWP2 may be proposed as a promising target of AML.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"85-95"},"PeriodicalIF":2.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stacey N Lee, Victoria Hoskin, Céline M Laumont, Shannon Snelling, Lorenzo Lindo, Lou Bird, Vera Samarkina, Chantale Thurston, Grace Fox, Sarah Ivanco, Megan Mahoney, Jeanette E Boudreau, Sarah Nersesian
{"title":"BioCanRx Summit for Cancer Immunotherapy 2022 Proceedings.","authors":"Stacey N Lee, Victoria Hoskin, Céline M Laumont, Shannon Snelling, Lorenzo Lindo, Lou Bird, Vera Samarkina, Chantale Thurston, Grace Fox, Sarah Ivanco, Megan Mahoney, Jeanette E Boudreau, Sarah Nersesian","doi":"10.1139/bcb-2023-0207","DOIUrl":"10.1139/bcb-2023-0207","url":null,"abstract":"<p><p>From 19 to 21 November 2022, BioCanRx held its first post-pandemic in-person Summit for Cancer Immunotherapy in Montreal, Canada. The meeting was well attended by patients, trainees, researchers, clinicians, and industry professionals, who came together to discuss the current state and future of biotherapeutics for cancer in Canada and beyond. Three plenaries, three keynote speakers, a lively debate, and panel discussions, together with poster sessions and a social event, made the event memorable and productive. The current state of cellular therapies, cellular engineering, clinical trials, and the role of the cancer microbiome were discussed in plenary session, and the patient voice was welcomed and present throughout the meeting, in large part due to the Learning Institute, a BioCanRx initiative to include patient partners in research. In this meeting review, we highlight the platform presentations, keynote speakers, debate combatants, panellists, and the patient perspective on the annual meeting.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-8"},"PeriodicalIF":2.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49688608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Crosstalk between chromatin, chromosomes, and epigenetics.","authors":"Alyssa Ialongo, Ssu-Yu Yeh, Ho Sung Rhee","doi":"10.1139/bcb-2023-0165","DOIUrl":"10.1139/bcb-2023-0165","url":null,"abstract":"<p><p>The International Asilomar Chromatin, Chromosomes, and Epigenetics Conference was held online from 8 to 10 December 2022. Topics of this year's conference included chromosome dysregulation, genome integrity, nuclear organization, regulation of chromatin, epigenetics, transcription, and gene regulation in cell differentiation and disease. The meeting featured four keynote speakers, including Yamini Dalal (National Cancer Institute, USA), Meaghan Jones (University of Manitoba, Canada), Pedro Rocha (National Institute of Child Health and Human Development, USA), and Vincent Pasque (University of Leuven, Belgium). The meeting brought together scientists at all career stages to present and discuss their work in the fields of chromatin and epigenetics.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"28-37"},"PeriodicalIF":2.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10112002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}