C/EBPβ-LIP Induces Cancer-Type Metabolic Reprogramming by Regulating the Let-7/LIN28B Circuit in Mice
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Role of CCCH-Type Zinc Finger Proteins in Human Adenovirus Infections
viruses Review Role of CCCH-Type Zinc Finger Proteins in Human Adenovirus Infections Zamaneh Hajikhezri 1, Mahmoud Darweesh 1,2, Göran Akusjärvi 1 and Tanel Punga 1,* 1 Department of Medical Biochemistry and Microbiology, Uppsala University, 75123 Uppsala, Sweden; [email protected] (Z.H.); [email protected] (M.D.); [email protected] (G.A.) 2 Department of Microbiology and Immunology, Al-Azhr University, Assiut 11651, Egypt * Correspondence: [email protected]; Tel.: +46-733-203-095 Received: 28 October 2020; Accepted: 16 November 2020; Published: 18 November 2020 Abstract: The zinc finger proteins make up a significant part of the proteome and perform a huge variety of functions in the cell. The CCCH-type zinc finger proteins have gained attention due to their unusual ability to interact with RNA and thereby control different steps of RNA metabolism. Since virus infections interfere with RNA metabolism, dynamic changes in the CCCH-type zinc finger proteins and virus replication are expected to happen. In the present review, we will discuss how three CCCH-type zinc finger proteins, ZC3H11A, MKRN1, and U2AF1, interfere with human adenovirus replication. We will summarize the functions of these three cellular proteins and focus on their potential pro- or anti-viral activities during a lytic human adenovirus infection. Keywords: human adenovirus; zinc finger protein; CCCH-type; ZC3H11A; MKRN1; U2AF1 1. Zinc Finger Proteins Zinc finger proteins are a big family of proteins with characteristic zinc finger (ZnF) domains present in the protein sequence. The ZnF domains consists of various ZnF motifs, which are short 30–100 amino acid sequences, coordinating zinc ions (Zn2+). -
Taf7l Cooperates with Trf2 to Regulate Spermiogenesis
Taf7l cooperates with Trf2 to regulate spermiogenesis Haiying Zhoua,b, Ivan Grubisicb,c, Ke Zhengd,e, Ying Heb, P. Jeremy Wangd, Tommy Kaplanf, and Robert Tjiana,b,1 aHoward Hughes Medical Institute and bDepartment of Molecular and Cell Biology, Li Ka Shing Center for Biomedical and Health Sciences, California Institute for Regenerative Medicine Center of Excellence, University of California, Berkeley, CA 94720; cUniversity of California Berkeley–University of California San Francisco Graduate Program in Bioengineering, University of California, Berkeley, CA 94720; dDepartment of Animal Biology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104; eState Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, People’s Republic of China; and fSchool of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem 91904, Israel Contributed by Robert Tjian, September 11, 2013 (sent for review August 20, 2013) TATA-binding protein (TBP)-associated factor 7l (Taf7l; a paralogue (Taf4b; a homolog of Taf4) (9), TBP-related factor 2 (Trf2) (10, of Taf7) and TBP-related factor 2 (Trf2) are components of the core 11), and Taf7l (12, 13). For example, mice bearing mutant or promoter complex required for gene/tissue-specific transcription deficient CREM showed decreased postmeiotic gene expression of protein-coding genes by RNA polymerase II. Previous studies and defective spermiogenesis (14). Mice deficient in Taf4b, reported that Taf7l knockout (KO) mice exhibit structurally abnor- a testis-specific homolog of Taf4, are initially normal but undergo mal sperm, reduced sperm count, weakened motility, and compro- progressive germ-cell loss and become infertile by 3 mo of age −/Y mised fertility. -
Binding Specificities of Human RNA Binding Proteins Towards Structured
bioRxiv preprint doi: https://doi.org/10.1101/317909; this version posted March 1, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Binding specificities of human RNA binding proteins towards structured and linear 2 RNA sequences 3 4 Arttu Jolma1,#, Jilin Zhang1,#, Estefania Mondragón4,#, Teemu Kivioja2, Yimeng Yin1, 5 Fangjie Zhu1, Quaid Morris5,6,7,8, Timothy R. Hughes5,6, Louis James Maher III4 and Jussi 6 Taipale1,2,3,* 7 8 9 AUTHOR AFFILIATIONS 10 11 1Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Solna, Sweden 12 2Genome-Scale Biology Program, University of Helsinki, Helsinki, Finland 13 3Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom 14 4Department of Biochemistry and Molecular Biology and Mayo Clinic Graduate School of 15 Biomedical Sciences, Mayo Clinic College of Medicine and Science, Rochester, USA 16 5Department of Molecular Genetics, University of Toronto, Toronto, Canada 17 6Donnelly Centre, University of Toronto, Toronto, Canada 18 7Edward S Rogers Sr Department of Electrical and Computer Engineering, University of 19 Toronto, Toronto, Canada 20 8Department of Computer Science, University of Toronto, Toronto, Canada 21 #Authors contributed equally 22 *Correspondence: [email protected] 23 24 25 SUMMARY 26 27 Sequence specific RNA-binding proteins (RBPs) control many important 28 processes affecting gene expression. They regulate RNA metabolism at multiple 29 levels, by affecting splicing of nascent transcripts, RNA folding, base modification, 30 transport, localization, translation and stability. Despite their central role in most 31 aspects of RNA metabolism and function, most RBP binding specificities remain 32 unknown or incompletely defined. -
Is Glyceraldehyde-3-Phosphate Dehydrogenase a Central Redox Mediator?
1 Is glyceraldehyde-3-phosphate dehydrogenase a central redox mediator? 2 Grace Russell, David Veal, John T. Hancock* 3 Department of Applied Sciences, University of the West of England, Bristol, 4 UK. 5 *Correspondence: 6 Prof. John T. Hancock 7 Faculty of Health and Applied Sciences, 8 University of the West of England, Bristol, BS16 1QY, UK. 9 [email protected] 10 11 SHORT TITLE | Redox and GAPDH 12 13 ABSTRACT 14 D-Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an immensely important 15 enzyme carrying out a vital step in glycolysis and is found in all living organisms. 16 Although there are several isoforms identified in many species, it is now recognized 17 that cytosolic GAPDH has numerous moonlighting roles and is found in a variety of 18 intracellular locations, but also is associated with external membranes and the 19 extracellular environment. The switch of GAPDH function, from what would be 20 considered as its main metabolic role, to its alternate activities, is often under the 21 influence of redox active compounds. Reactive oxygen species (ROS), such as 22 hydrogen peroxide, along with reactive nitrogen species (RNS), such as nitric oxide, 23 are produced by a variety of mechanisms in cells, including from metabolic 24 processes, with their accumulation in cells being dramatically increased under stress 25 conditions. Overall, such reactive compounds contribute to the redox signaling of the 26 cell. Commonly redox signaling leads to post-translational modification of proteins, 27 often on the thiol groups of cysteine residues. In GAPDH the active site cysteine can 28 be modified in a variety of ways, but of pertinence, can be altered by both ROS and 29 RNS, as well as hydrogen sulfide and glutathione. -
TCTE1 Is a Conserved Component of the Dynein Regulatory Complex and Is Required for Motility and Metabolism in Mouse Spermatozoa
TCTE1 is a conserved component of the dynein PNAS PLUS regulatory complex and is required for motility and metabolism in mouse spermatozoa Julio M. Castanedaa,b,1, Rong Huac,d,1, Haruhiko Miyatab, Asami Ojib,e, Yueshuai Guoc,d, Yiwei Chengc,d, Tao Zhouc,d, Xuejiang Guoc,d, Yiqiang Cuic,d, Bin Shenc, Zibin Wangc, Zhibin Huc,f, Zuomin Zhouc,d, Jiahao Shac,d, Renata Prunskaite-Hyyrylainena,g,h, Zhifeng Yua,i, Ramiro Ramirez-Solisj, Masahito Ikawab,e,k,2, Martin M. Matzuka,g,i,l,m,n,2, and Mingxi Liuc,d,2 aDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030; bResearch Institute for Microbial Diseases, Osaka University, Suita, Osaka 5650871, Japan; cState Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, People’s Republic of China; dDepartment of Histology and Embryology, Nanjing Medical University, Nanjing 210029, People’s Republic of China; eGraduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 5650871, Japan; fAnimal Core Facility of Nanjing Medical University, Nanjing 210029, People’s Republic of China; gCenter for Reproductive Medicine, Baylor College of Medicine, Houston, TX 77030; hFaculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu FI-90014, Finland; iCenter for Drug Discovery, Baylor College of Medicine, Houston, TX 77030; jWellcome Trust Sanger Institute, Hinxton CB10 1SA, United Kingdom; kThe Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 1088639, Japan; lDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030; mDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030; and nDepartment of Pharmacology, Baylor College of Medicine, Houston, TX 77030 Contributed by Martin M. -
RC3H1 Antibody (C-Term) Affinity Purified Rabbit Polyclonal Antibody (Pab) Catalog # Ap14162b
10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 RC3H1 Antibody (C-term) Affinity Purified Rabbit Polyclonal Antibody (Pab) Catalog # AP14162b Specification RC3H1 Antibody (C-term) - Product Information Application WB, IHC-P,E Primary Accession Q5TC82 Other Accession Q6NUC6, Q4VGL6, NP_742068.1 Reactivity Human Predicted Mouse, Xenopus Host Rabbit Clonality Polyclonal Isotype Rabbit Ig Calculated MW 125736 Antigen Region 1015-1043 RC3H1 Antibody (C-term) - Additional Information RC3H1 Antibody (C-term) (Cat. #AP14162b) western blot analysis in NCI-H460 cell line Gene ID 149041 lysates (35ug/lane).This demonstrates the RC3H1 antibody detected the RC3H1 protein Other Names (arrow). Roquin-1, Roquin, RING finger and C3H zinc finger protein 1, RING finger and CCCH-type zinc finger domain-containing protein 1, RING finger protein 198, RC3H1, KIAA2025, RNF198 Target/Specificity This RC3H1 antibody is generated from rabbits immunized with a KLH conjugated synthetic peptide between 1015-1043 amino acids from the C-terminal region of human RC3H1. Dilution WB~~1:1000 IHC-P~~1:10~50 Format Purified polyclonal antibody supplied in PBS with 0.09% (W/V) sodium azide. This RC3H1 Antibody (C-term) antibody is purified through a protein A (AP14162b)immunohistochemistry analysis in column, followed by peptide affinity formalin fixed and paraffin embedded human purification. kidney tissue followed by peroxidase conjugation of the secondary antibody and Storage DAB staining.This data demonstrates the use Maintain refrigerated at 2-8°C for up to 2 of RC3H1 Antibody (C-term) for weeks. For long term storage store at -20°C immunohistochemistry. -
RC3H1 Antibody Catalog # ASC11623
10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 RC3H1 Antibody Catalog # ASC11623 Specification RC3H1 Antibody - Product Information Application WB, IHC, IF Primary Accession Q5TC82 Other Accession NP_742068, 73695473 Reactivity Human, Mouse, Rat Host Rabbit Clonality Polyclonal Isotype IgG Calculated MW 125 kDa KDa Application Notes RC3H1 antibody can be used for detection of RC3H1 by Western blot at 1 - 2 µg/mL. Western blot analysis of RC3H1 in HeLa cell lysate with RC3H1 antibody at 1 µg/mL RC3H1 Antibody - Additional Information Gene ID 149041 Target/Specificity RC3H1; At least three isoforms of RC3H1 are known to exist; this antibody will detect all three isoforms. Reconstitution & Storage RC3H1 antibody can be stored at 4℃ for three months and -20℃, stable for up to one year. Precautions RC3H1 Antibody is for research use only Immunohistochemistry of RC3H1 in human and not for use in diagnostic or therapeutic procedures. small intestine tissue with RC3H1 antibody at 5 µg/ml. RC3H1 Antibody - Protein Information Name RC3H1 (HGNC:29434) Synonyms KIAA2025, RNF198 Function Post-transcriptional repressor of mRNAs containing a conserved stem loop motif, Page 1/3 10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 called constitutive decay element (CDE), which is often located in the 3'-UTR, as in HMGXB3, ICOS, IER3, NFKBID, NFKBIZ, PPP1R10, TNF, TNFRSF4 and in many more mRNAs (PubMed:<a href="http://www.unipr ot.org/citations/25026078" target="_blank">25026078</a>). Cleaves translationally inactive mRNAs harboring a stem-loop (SL), often located in their 3'-UTRs, during the early phase of inflammation in a helicase UPF1-independent manner (By similarity). -
Biomarker Discovery by Integrated Joint Non-Negative Matrix Factorization and Pathway Signature Analyses
www.nature.com/scientificreports OPEN Biomarker discovery by integrated joint non-negative matrix factorization and pathway Received: 13 December 2017 Accepted: 15 June 2018 signature analyses Published: xx xx xxxx Naoya Fujita1,2,3, Shinji Mizuarai2, Katsuhiko Murakami1 & Kenta Nakai 1,3 Predictive biomarkers are important for selecting appropriate patients for particular treatments. Comprehensive genomic, transcriptomic, and pharmacological data provide clues for understanding relationships between biomarkers and drugs. However, it is still difcult to mine biologically meaningful biomarkers from multi-omics data. Here, we developed an approach for mining multi-omics cell line data by integrating joint non-negative matrix factorization (JNMF) and pathway signature analyses to identify candidate biomarkers. The JNMF detected known associations between biomarkers and drugs such as BRAF mutation with PLX4720 and HER2 amplifcation with lapatinib. Furthermore, we observed that tumours with both BRAF mutation and MITF activation were more sensitive to BRAF inhibitors compared to tumours with BRAF mutation without MITF activation. Therefore, activation of the BRAF/ MITF axis seems to be a more appropriate biomarker for predicting the efcacy of a BRAF inhibitor than the conventional biomarker of BRAF mutation alone. Our biomarker discovery scheme represents an integration of JNMF multi-omics clustering and multi-layer interpretation based on pathway gene signature analyses. This approach is also expected to be useful for establishing drug development strategies, identifying pharmacodynamic biomarkers, in mode of action analysis, as well as for mining drug response data in a clinical setting. Precision medicine for cancer patients with molecular targeted drugs and predictive biomarkers is expected to lead to a paradigm shif from one-size-fts-all medicine to patient-specifc medicine1. -
Potential Molecular Mechanisms of Chaihu-Shugan-San in Treatment of Breast Cancer Based on Network Pharmacology
Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2020, Article ID 3670309, 9 pages https://doi.org/10.1155/2020/3670309 Research Article Potential Molecular Mechanisms of Chaihu-Shugan-San in Treatment of Breast Cancer Based on Network Pharmacology Kunmin Xiao,1,2 Kexin Li,1 Sidan Long,1 Chenfan Kong,1 and Shijie Zhu 1,2 1Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China 2Department of Oncology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, China Correspondence should be addressed to Shijie Zhu; [email protected] Received 16 May 2020; Accepted 5 August 2020; Published 25 September 2020 Guest Editor: Azis Saifudin Copyright © 2020 Kunmin Xiao et al. /is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Breast cancer is one of the most common cancers endangering women’s health all over the world. Traditional Chinese medicine is increasingly recognized as a possible complementary and alternative therapy for breast cancer. Chaihu-Shugan-San is a traditional Chinese medicine prescription, which is extensively used in clinical practice. Its therapeutic effect on breast cancer has attracted extensive attention, but its mechanism of action is still unclear. In this study, we explored the molecular mechanism of Chaihu- Shugan-San in the treatment of breast cancer by network pharmacology. /e results showed that 157 active ingredients and 8074 potential drug targets were obtained in the TCMSP database according to the screening conditions. 2384 disease targets were collected in the TTD, OMIM, DrugBank, GeneCards disease database. -
The Writers, Readers, and Erasers in Redox Regulation of GAPDH
antioxidants Review The Writers, Readers, and Erasers in Redox Regulation of GAPDH Maria-Armineh Tossounian, Bruce Zhang and Ivan Gout * Department of Structural and Molecular Biology, University College London, London WC1E 6BT, UK; [email protected] (M.-A.T.); [email protected] (B.Z.) * Correspondence: [email protected] Received: 23 October 2020; Accepted: 14 December 2020; Published: 16 December 2020 Abstract: Glyceraldehyde 3–phosphate dehydrogenase (GAPDH) is a key glycolytic enzyme, which is crucial for the breakdown of glucose to provide cellular energy. Over the past decade, GAPDH has been reported to be one of the most prominent cellular targets of post-translational modifications (PTMs), which divert GAPDH toward different non-glycolytic functions. Hence, it is termed a moonlighting protein. During metabolic and oxidative stress, GAPDH is a target of different oxidative PTMs (oxPTM), e.g., sulfenylation, S-thiolation, nitrosylation, and sulfhydration. These modifications alter the enzyme’s conformation, subcellular localization, and regulatory interactions with downstream partners, which impact its glycolytic and non-glycolytic functions. In this review, we discuss the redox regulation of GAPDH by different redox writers, which introduce the oxPTM code on GAPDH to instruct a redox response; the GAPDH readers, which decipher the oxPTM code through regulatory interactions and coordinate cellular response via the formation of multi-enzyme signaling complexes; and the redox erasers, which are the reducing systems that regenerate the GAPDH catalytic activity. Human pathologies associated with the oxidation-induced dysregulation of GAPDH are also discussed, featuring the importance of the redox regulation of GAPDH in neurodegeneration and metabolic disorders. -
Genome-Wide Association Studies in Alzheimer Disease
NEUROLOGICAL REVIEW Genome-Wide Association Studies in Alzheimer Disease Stephen C. Waring, DVM, PhD; Roger N. Rosenberg, MD he genetics of Alzheimer disease (AD) to date support an age-dependent dichotomous model whereby earlier age of disease onset (Ͻ60 years) is explained by 3 fully penetrant genes (APP [NCBI Entrez gene 351], PSEN1 [NCBI Entrez gene 5663], and PSEN2 [NCBI Entrez gene 5664]), whereas later age of disease onset (Ն65 years) representing most cases Tof AD has yet to be explained by a purely genetic model. The APOE gene (NCBI Entrez gene 348) is the strongest genetic risk factor for later onset, although it is neither sufficient nor necessary to ex- plain all occurrences of disease. Numerous putative genetic risk alleles and genetic variants have been reported. Although all have relevance to biological mechanisms that may be associated with AD patho- genesis, they await replication in large representative populations. Genome-wide association studies have emerged as an increasingly effective tool for identifying genetic contributions to complex dis- eases and represent the next frontier for furthering our understanding of the underlying etiologic, bio- logical, and pathologic mechanisms associated with chronic complex disorders. There have already been success stories for diseases such as macular degeneration and diabetes mellitus. Whether this will hold true for a genetically complex and heterogeneous disease such as AD is not known, al- though early reports are encouraging. This review considers recent publications from studies that have successfully applied genome-wide association methods to investigations of AD by taking advantage of the currently available high-throughput arrays, bioinformatics, and software advances. -
Mouse Rc3h1 Conditional Knockout Project (CRISPR/Cas9)
https://www.alphaknockout.com Mouse Rc3h1 Conditional Knockout Project (CRISPR/Cas9) Objective: To create a Rc3h1 conditional knockout mouse model (C57BL/6N) by CRISPR/Cas-mediated genome engineering. Strategy summary: The Rc3h1 gene (NCBI Reference Sequence: NM_001024952 ; Ensembl: ENSMUSG00000040423 ) is located on mouse chromosome 1. 20 exons are identified, with the ATG start codon in exon 2 and the TAG stop codon in exon 20 (Transcript: ENSMUST00000161609). Exon 3 will be selected as conditional knockout region (cKO region). Deletion of this region should result in the loss of function of the mouse Rc3h1 gene. To engineer the targeting vector, homologous arms and cKO region will be generated by PCR using BAC clone RP23-162J18 as template. Cas9, gRNA and targeting vector will be co-injected into fertilized eggs for cKO mouse production. The pups will be genotyped by PCR followed by sequencing analysis. Note: A single recessive mutation on this gene resulted in severe autoimmune disease with phenotype resembling human systemic lupus erythematosus. Exon 3 starts from about 6.84% of the coding region. The knockout of Exon 3 will result in frameshift of the gene. The size of intron 2 for 5'-loxP site insertion: 7767 bp, and the size of intron 3 for 3'-loxP site insertion: 1762 bp. The size of effective cKO region: ~621 bp. The cKO region does not have any other known gene. Page 1 of 7 https://www.alphaknockout.com Overview of the Targeting Strategy Wildtype allele gRNA region 5' gRNA region 3' 1 3 4 20 Targeting vector Targeted allele Constitutive KO allele (After Cre recombination) Legends Exon of mouse Rc3h1 Homology arm cKO region loxP site Page 2 of 7 https://www.alphaknockout.com Overview of the Dot Plot Window size: 10 bp Forward Reverse Complement Note: The sequence of homologous arms and cKO region is aligned with itself to determine if there are tandem repeats.