A Gene-Set Enrichment and Protein–Protein Interaction Network-Based
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Autism Multiplex Family with 16P11.2P12.2 Microduplication Syndrome in Monozygotic Twins and Distal 16P11.2 Deletion in Their Brother
European Journal of Human Genetics (2012) 20, 540–546 & 2012 Macmillan Publishers Limited All rights reserved 1018-4813/12 www.nature.com/ejhg ARTICLE Autism multiplex family with 16p11.2p12.2 microduplication syndrome in monozygotic twins and distal 16p11.2 deletion in their brother Anne-Claude Tabet1,2,3,4, Marion Pilorge2,3,4, Richard Delorme5,6,Fre´de´rique Amsellem5,6, Jean-Marc Pinard7, Marion Leboyer6,8,9, Alain Verloes10, Brigitte Benzacken1,11,12 and Catalina Betancur*,2,3,4 The pericentromeric region of chromosome 16p is rich in segmental duplications that predispose to rearrangements through non-allelic homologous recombination. Several recurrent copy number variations have been described recently in chromosome 16p. 16p11.2 rearrangements (29.5–30.1 Mb) are associated with autism, intellectual disability (ID) and other neurodevelopmental disorders. Another recognizable but less common microdeletion syndrome in 16p11.2p12.2 (21.4 to 28.5–30.1 Mb) has been described in six individuals with ID, whereas apparently reciprocal duplications, studied by standard cytogenetic and fluorescence in situ hybridization techniques, have been reported in three patients with autism spectrum disorders. Here, we report a multiplex family with three boys affected with autism, including two monozygotic twins carrying a de novo 16p11.2p12.2 duplication of 8.95 Mb (21.28–30.23 Mb) characterized by single-nucleotide polymorphism array, encompassing both the 16p11.2 and 16p11.2p12.2 regions. The twins exhibited autism, severe ID, and dysmorphic features, including a triangular face, deep-set eyes, large and prominent nasal bridge, and tall, slender build. The eldest brother presented with autism, mild ID, early-onset obesity and normal craniofacial features, and carried a smaller, overlapping 16p11.2 microdeletion of 847 kb (28.40–29.25 Mb), inherited from his apparently healthy father. -
Chronic Exposure of Humans to High Level Natural Background Radiation Leads to Robust Expression of Protective Stress Response Proteins S
www.nature.com/scientificreports OPEN Chronic exposure of humans to high level natural background radiation leads to robust expression of protective stress response proteins S. Nishad1,2, Pankaj Kumar Chauhan3, R. Sowdhamini3 & Anu Ghosh1,2* Understanding exposures to low doses of ionizing radiation are relevant since most environmental, diagnostic radiology and occupational exposures lie in this region. However, the molecular mechanisms that drive cellular responses at these doses, and the subsequent health outcomes, remain unclear. A local monazite-rich high level natural radiation area (HLNRA) in the state of Kerala on the south-west coast of Indian subcontinent show radiation doses extending from ≤ 1 to ≥ 45 mGy/y and thus, serve as a model resource to understand low dose mechanisms directly on healthy humans. We performed quantitative discovery proteomics based on multiplexed isobaric tags (iTRAQ) coupled with LC–MS/MS on human peripheral blood mononuclear cells from HLNRA individuals. Several proteins involved in diverse biological processes such as DNA repair, RNA processing, chromatin modifcations and cytoskeletal organization showed distinct expression in HLNRA individuals, suggestive of both recovery and adaptation to low dose radiation. In protein–protein interaction (PPI) networks, YWHAZ (14-3-3ζ) emerged as the top-most hub protein that may direct phosphorylation driven pro- survival cellular processes against radiation stress. PPI networks also identifed an integral role for the cytoskeletal protein ACTB, signaling protein PRKACA; and the molecular chaperone HSPA8. The data will allow better integration of radiation biology and epidemiology for risk assessment [Data are available via ProteomeXchange with identifer PXD022380]. Te basic principles of low linear energy transfer (LET) ionizing radiation (IR) induced efects on mammalian systems have been broadly explored and there exists comprehensive knowledge on the health efects of high doses of IR delivered at high dose rates. -
Structural Characterisation of the Interaction Between RBBP6 and The
Structural characterisation of the interaction between RBBP6 and the multifunctional protein YB-1 by Victor Muleya A thesis submitted in partial fulfilment of the requirements of the M.Sc. Degree in Biotechnology at the Department of Biotechnology, Faculty of Science, University of the Western Cape. Supervisor: Dr. David J.R. Pugh October 2010 i Keywords: RBBP6 YB-1 Interaction RING 15N-HSQC NMR Yeast 2-hybrid Co-immunoprecipitation Homodimerisation Ubiquitination i Abstract Structural characterisation of the interaction between RBBP6 and the multifunctional protein YB-1 Victor Muleya M.Sc. (Biotechnology) thesis, Department of Biotechnology, Faculty of Natural Sciences, University of the Western Cape. Retinoblastoma binding protein 6 (RBBP6) is a 250 kDa RING finger-containing protein whose function is known to be mediated through interaction with other proteins. RBBP6 plays a role in the regulation of the tumour suppressor protein p53 and is also thought to be involved in mRNA splicing although its role has yet to be characterised. A recent study utilising a yeast 2-hybrid screen identified the cancer-associated protein known as YB-1 as an interacting partner of RBBP6, and showed that RBBP6 ubiquitinates YB-1, leading to its degradation in the proteasome. Human Y-box binding protein 1 (YB-1) is member of the cold-shock domain family of proteins, which regulates a number of growth related genes through both transcriptional and translational mechanisms. YB-1 is a cell-survival factor whose expression is increased in proliferating normal and cancer cells. It also protects cells against p53-mediated apoptosis by repressing the p53- promoter and down-regulating endogenous p53. -
Itraq‑Based Proteomics Analysis of the Therapeutic Effects of Combined Anticancer Bioactive Peptides and Oxaliplatin on Gastric Cancer Cells
ONCOLOGY REPORTS 43: 201-217, 2020 iTRAQ‑based proteomics analysis of the therapeutic effects of combined anticancer bioactive peptides and oxaliplatin on gastric cancer cells YANAN XU1, XIAN LI2 and XIULAN SU1,2 1Department of Cell Biology, College of Basic Medicine, Capital Medical University, Beijing 100069; 2Clinical Medical Research Center, The Affiliated Hospital of Inner Mongolia Medical University, Inner Mongolia Autonomous Region 010050, P.R. China Received April 2, 2019; Accepted September 25, 2019 DOI: 10.3892/or.2019.7406 Abstract. The combination of chemotherapeutic modalities cells treated with ACBP, OXA and ACBP-OXA exhibited 17 may be more effective in treating gastric cancer compared (10 up- and 7 downregulated), 111 (27 up- and 84 downregu- with any modality alone. Previous studies have demonstrated lated) and 128 (53 up- and 75 downregulated) differentially that the combination of anticancer bioactive peptides (ACBP) expressed proteins, respectively. Of the 256 differentially and oxaliplatin (OXA) significantly inhibited the growth of the expressed proteins, 6 (TPX2, NUSAP1, TOP2A, YAP, MKi-67 gastric cancer cell line MKN-45, promoted the apoptosis of and GPC4) were verified by the parallel reaction monitoring MKN-45 cells, and caused an irreversible arrest of the MKN-45 method, which revealed that TPX2, NUSAP1, TOP2A, YAP, cell cycle in the G2/M phase. In the present study, an isobaric MKi-67 and GPC4 expression decreased with ACBP-OXA tag for relative and absolute quantitation (iTRAQ)-based treatment. The cellular localization, functional annotation and quantitative proteomics technique was used to determine the biological pathways of differentially expressed proteins were effect of ACBP-OXA treatment on the proteomics profile examined by Gene Ontology and Kyoto Encyclopedia of Genes of MKN-45 cells. -
Dynamic Interplay Between Locus-Specific DNA Methylation and Hydroxymethylation Regulates Distinct Biological Pathways in Prostate Carcinogenesis Shivani N
Kamdar et al. Clinical Epigenetics (2016) 8:32 DOI 10.1186/s13148-016-0195-4 RESEARCH Open Access Dynamic interplay between locus-specific DNA methylation and hydroxymethylation regulates distinct biological pathways in prostate carcinogenesis Shivani N. Kamdar1,2, Linh T. Ho1, Ken J. Kron1, Ruth Isserlin3, Theodorus van der Kwast1,4, Alexandre R. Zlotta5, Neil E. Fleshner6, Gary Bader3 and Bharati Bapat1,2* Abstract Background: Despite the significant global loss of DNA hydroxymethylation marks in prostate cancer tissues, the locus-specific role of hydroxymethylation in prostate tumorigenesis is unknown. We characterized hydroxymethylation and methylation marks by performing whole-genome next-generation sequencing in representative normal and prostate cancer-derived cell lines in order to determine functional pathways and key genes regulated by these epigenomic modifications in cancer. Results: Our cell line model shows disruption of hydroxymethylation distribution in cancer, with global loss and highly specific gain in promoter and CpG island regions. Significantly, we observed locus-specific retention of hydroxymethylation marks in specific intronic and intergenic regions which may play a novel role in the regulation of gene expression in critical functional pathways, such as BARD1 signaling and steroid hormone receptor signaling in cancer. We confirm a modest correlation of hydroxymethylation with expression in intragenic regions in prostate cancer, while identifying an original role for intergenic hydroxymethylation in differentially expressed regulatory pathways in cancer. We also demonstrate a successful strategy for the identification and validation of key candidate genes from differentially regulated biological pathways in prostate cancer. Conclusions: Our results indicate a distinct function for aberrant hydroxymethylation within each genomic feature in cancer, suggesting a specific and complex role for the deregulation of hydroxymethylation in tumorigenesis, similar to methylation. -
DDB1 Functions As a Linker to Recruit Receptor WD40 Proteins to CUL4− ROC1 Ubiquitin Ligases
Downloaded from genesdev.cshlp.org on October 6, 2021 - Published by Cold Spring Harbor Laboratory Press RESEARCH COMMUNICATION domain to bind with a conserved protein motif, the F DDB1 functions as a linker box, which, via its additional protein–protein interaction to recruit receptor WD40 modules, recruits various substrates, often phosphory- lated, to the CUL1–ROC1 catalytic core. To bring spe- proteins to CUL4–ROC1 cific substrates to CUL2- and CUL5-dependent ligases, a ubiquitin ligases heterodimeric linker complex containing elongins B and C binds simultaneously to an analogous N-terminal do- Yizhou Joseph He, Chad M. McCall, Jian Hu, main in CUL2 and CUL5 and to two similar protein 1 motifs, the VHL box and SOCS box. VHL and SOCS pro- Yaxue Zeng, and Yue Xiong teins, via their additional protein–protein interaction Lineberger Comprehensive Cancer Center, Department of modules, target various substrates differentially to the Biochemistry and Biophysics, Program in Molecular Biology CUL2–ROC1 or CUL5–ROC2 catalytic cores (Kamura et and Biotechnology, University of North Carolina, Chapel Hill, al. 1998, 2001, 2004; Stebbins et al. 1999; Zhang et al. North Carolina 27599, USA 1999). Omitting a linker, CUL3 utilizes its N-terminal domain to bind to proteins with a conserved 100-residue Cullins assemble the largest family of ubiquitin ligases protein motif known as a BTB domain, which, via addi- by binding with ROC1 and various substrate receptors. tional protein–protein interaction domains, then target CUL4 function is linked with many cellular processes, various substrates to the CUL3–ROC1 catalytic core (Fu- rukawa et al. 2003; Geyer et al. -
Downloaded with Ma- Disease D D
bioRxiv preprint doi: https://doi.org/10.1101/483065; this version posted November 29, 2018. 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. F1000Research 2016 - DRAFT ARTICLE (PRE-SUBMISSION) Bioinformatics Approach to Identify Diseasome and Co- morbidities Effect of Mitochondrial Dysfunctions on the Progression of Neurological Disorders Md. Shahriare Satu1, Koushik Chandra Howlader2, Tajim Md. Niamat Ullah Akhund3, Fazlul Huq4, Julian M.W. Quinn5, and Mohammad Ali Moni4,5 1Dept. of CSE, Gono Bishwabidyalay, Dhaka, Bangladesh 2Dept. of CSTE, Noakhali Science and Technology University, Noakhali, Bangladesh 3Institute of Information Technology, Jahangirnagar University, Dhaka, Bangladesh 4School of Biomedical Science, Faculty of Medicine and Health, The University of Sydney, Australia 5Bone Biology Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia Abstract Mitochondrial dysfunction can cause various neurological diseases. We therefore developed a quantitative framework to explore how mitochondrial dysfunction may influence the progression of Alzheimer’s, Parkinson’s, Hunting- ton’s and Lou Gehrig’s diseases and cerebral palsy through analysis of genes showing altered expression in these conditions. We sought insights about the gene profiles of mitochondrial and associated neurological diseases by investigating gene-disease networks, KEGG pathways, gene ontologies and protein-protein interaction network. Gene disease networks were constructed to connect shared genes which are commonly found between the neurological diseases and Mito- chondrial Dysfunction. We also generated KEGG pathways and gene ontologies to explore functional enrichment among them, and protein-protein interaction networks to identify the shared protein groups of these diseases. -
Expression and Purification of Functional Recombinant CUL2
www.nature.com/scientificreports OPEN Expression and purifcation of functional recombinant CUL2•RBX1 from E. coli Stephanie Diaz1, Lihong Li1,2, Kankan Wang1 & Xing Liu1,2* Cullin-2 (CUL2) based cullin-RING ligases (CRL2s) comprise a family of ubiquitin E3 ligases that exist only in multi-cellular organisms and are crucial for cellular processes such as embryogenesis and viral pathogenesis. CUL2 is the scafold protein that binds one of the interchangeable substrate receptor modules, which consists of adaptor proteins and the substrate receptor protein. The VHL protein is a substrate receptor known to target hypoxia-inducible factor α (HIF1α) for ubiquitination and degradation. Because of its critical role in the ubiquitination of important cellular factors such as HIF1α, CRL2s have been investigated for their biological functions and the development of novel therapeutics against diseases. Given the importance of CRL2s in biological and biomedical research, methods that efciently produce functional CUL2 proteins will greatly facilitate studies on the mechanism and regulation of CRL2s. Here, we report two cost-efective systems for the expression and purifcation of recombinant human CUL2 from E. coli cells. The purifed CUL2 proteins were ~ 95% pure, could bind their substrate receptor modules, and were enzymatically active in transferring ubiquitin or ubiquitin-like protein to the corresponding substrate in in vitro assays. The presented methodological advancements will help advance research in CRL2 function and regulation. Protein turnover is a cellular regulatory system defned by the continuous synthesis and decomposition of specifc proteins to maintain the integrity of optimally functioning proteins 1,2. Abnormalities during protein turnover, specifcally during protein degradation, ofen result in human diseases such as cystic fbrosis and liposarcoma. -
Investigation of the Intra-Cellular Localisation of Retinoblastoma Binding Protein 6 Using Immunofluorescence Microscopy
Investigation of the intra-cellular localisation of Retinoblastoma Binding Protein 6 using immunofluorescence microscopy Anna Victoria Szmyd-Potapczuk A thesis submitted in fulfilment of the requirement for the degree of Doctor Philosophiae in the Faculty of Natural Science, University of the Western Cape Supervisor: Prof David JR Pugh September 2017 I ABSTRACT Investigation of the intra-cellular localisation of Retinoblastoma Binding Protein 6 using immunofluorescence microscopy AV Szmyd-Potapczuk PhD thesis, Department of Biotechnology, Faculty of Natural Science, University of the Western Cape Human Retinoblastoma Binding Protein 6 (RBBP6) is a 200 kDa protein that has been implicated in a number of crucial cellular processes. It forms part of the mRNA 3'-end processing complex in both humans and yeast, and it contains an RS-like domain and interacts with core splicing proteins, suggesting multiple roles in mRNA processing. Through its RING finger domain it has been implicated in catalysing ubiquitination of the tumour suppressor p53, the oncogene Y-Box Binding Protein 1 (YB-1) and the DNA replication-associated protein zBTB38. It is one of only a few proteins known to bind to both p53 and pRb. At the N-terminus of the protein is the DWNN domain, an ubiquitin-like domain which is found only in this protein family. Four protein isoforms of RBBP6 have been identified in humans, all of which contain the DWNN domain: isoform 1 contains 1972 residues, isoform 2 contains 1758 residues and isoform 4 contains 952 residues. Isoform 3, which contains the first 101 residues of the full length protein (isoform 1), including the DWNN domain, followed by an unique 17-amino acid tail, is reported to be expressed independently of the other isoforms and to be down-regulated in a number of cancers. -
Mechanisms of Action of Coxiella Burnetii Effectors Inferred from Host-Pathogen Protein Interactions
RESEARCH ARTICLE Mechanisms of action of Coxiella burnetii effectors inferred from host-pathogen protein interactions Anders Wallqvist1, Hao Wang1, Nela Zavaljevski1, Vesna MemisÏević1, Keehwan Kwon2, Rembert Pieper2, Seesandra V. Rajagopala2, Jaques Reifman1* 1 Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command, Fort Detrick, Maryland, United States of America, 2 J. Craig Venter Institute, Rockville, Maryland, United States of America a1111111111 a1111111111 * [email protected] a1111111111 a1111111111 a1111111111 Abstract Coxiella burnetii is an obligate Gram-negative intracellular pathogen and the etiological agent of Q fever. Successful infection requires a functional Type IV secretion system, which OPEN ACCESS translocates more than 100 effector proteins into the host cytosol to establish the infection, Citation: Wallqvist A, Wang H, Zavaljevski N, restructure the intracellular host environment, and create a parasitophorous vacuole where MemisÏević V, Kwon K, Pieper R, et al. (2017) the replicating bacteria reside. We used yeast two-hybrid (Y2H) screening of 33 selected C. Mechanisms of action of Coxiella burnetii effectors burnetii effectors against whole genome human and murine proteome libraries to generate inferred from host-pathogen protein interactions. a map of potential host-pathogen protein-protein interactions (PPIs). We detected 273 PLoS ONE 12(11): e0188071. https://doi.org/ 10.1371/journal.pone.0188071 unique interactions between 20 pathogen and 247 human proteins, and 157 between 17 pathogen and 137 murine proteins. We used orthology to combine the data and create a sin- Editor: Zhao-Qing Luo, Purdue University, UNITED STATES gle host-pathogen interaction network containing 415 unique interactions between 25 C. -
Anti-RBBP6 Antibody (ARG41302)
Product datasheet [email protected] ARG41302 Package: 50 μg anti-RBBP6 antibody Store at: -20°C Summary Product Description Rabbit Polyclonal antibody recognizes RBBP6 Tested Reactivity Hu, Ms Tested Application ICC/IF, IHC-P, WB Host Rabbit Clonality Polyclonal Isotype IgG Target Name RBBP6 Antigen Species Human Immunogen Recombinant protein corresponding to aa. 97-351 of Human RBBP6. Conjugation Un-conjugated Alternate Names PACT; Retinoblastoma-binding protein 6; E3 ubiquitin-protein ligase RBBP6; EC 6.3.2.-; SNAMA; Proliferation potential-related protein; RBQ-1; Protein P2P-R; Retinoblastoma-binding Q protein 1; MY038; P2P-R; p53-associated cellular protein of testis Application Instructions Application table Application Dilution ICC/IF 1:100 IHC-P 1:100 WB 2 - 5 µg/ml Application Note * The dilutions indicate recommended starting dilutions and the optimal dilutions or concentrations should be determined by the scientist. Positive Control Mouse brain Calculated Mw 202 kDa Properties Form Liquid Purification Purification with Protein G. Buffer 0.01M PBS (pH 7.4), 0.03% Proclin 300 and 50% Glycerol. Preservative 0.03% Proclin 300 Stabilizer 50% Glycerol Storage instruction For continuous use, store undiluted antibody at 2-8°C for up to a week. For long-term storage, aliquot and store at -20°C. Storage in frost free freezers is not recommended. Avoid repeated freeze/thaw cycles. Suggest spin the vial prior to opening. The antibody solution should be gently mixed before use. www.arigobio.com 1/3 Note For laboratory research only, not for drug, diagnostic or other use. Bioinformation Gene Symbol RBBP6 Gene Full Name retinoblastoma binding protein 6 Background The retinoblastoma tumor suppressor (pRB) protein binds with many other proteins. -
The Structure and Regulation of Cullin 2 Based E3 Ubiquitin Ligases and Their Biological Functions Weijia Cai* and Haifeng Yang*
Cai and Yang Cell Div (2016) 11:7 DOI 10.1186/s13008-016-0020-7 Cell Division REVIEW Open Access The structure and regulation of Cullin 2 based E3 ubiquitin ligases and their biological functions Weijia Cai* and Haifeng Yang* Abstract Background: Cullin-RING E3 ubiquitin ligase complexes play a central role in targeting cellular proteins for ubiquit- ination-dependent protein turnover through 26S proteasome. Cullin-2 is a member of the Cullin family, and it serves as a scaffold protein for Elongin B and C, Rbx1 and various substrate recognition receptors to form E3 ubiquitin ligases. Main body of the abstract: First, the composition, structure and the regulation of Cullin-2 based E3 ubiquitin ligases were introduced. Then the targets, the biological functions of complexes that use VHL, Lrr-1, Fem1b, Prame, Zyg-11, BAF250, Rack1 as substrate targeting subunits were described, and their involvement in diseases was discussed. A small molecule inhibitor of Cullins as a potential anti-cancer drug was introduced. Furthermore, proteins with VHL box that might bind to Cullin-2 were described. Finally, how different viral proteins form E3 ubiquitin ligase complexes with Cullin-2 to counter host viral defense were explained. Conclusions: Cullin-2 based E3 ubiquitin ligases, using many different substrate recognition receptors, recognize a number of substrates and regulate their protein stability. These complexes play critical roles in biological processes and diseases such as cancer, germline differentiation and viral defense. Through the better understanding of their biology, we can devise and develop new therapeutic strategies to treat cancers, inherited diseases and viral infections.