Publications by authors named "Yaqoub Ashhab"

16 Publications

  • Page 1 of 1

Identification of Highly Conserved SARS-CoV-2 Antigenic Epitopes with Wide Coverage Using Reverse Vaccinology Approach.

Viruses 2021 04 28;13(5). Epub 2021 Apr 28.

Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea.

One of the most effective strategies for eliminating new and emerging infectious diseases is effective immunization. The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) warrants the need for a maximum coverage vaccine. Moreover, mutations that arise within the virus have a significant impact on the vaccination strategy. Here, we built a comprehensive workflow pipeline to identify B-cell- and T-cell-stimulating antigens of SARS-CoV-2 viral proteins. Our reverse vaccinology (RV) approach consisted of two parts: (1) analysis of the selected viral proteins based on annotated cellular location, antigenicity, allele coverage, epitope density, and mutation density and (2) analysis of the various aspects of the epitopes, including antigenicity, allele coverage, IFN-γ induction, toxicity, host homology, and site mutational density. After performing a mutation analysis based on the contemporary mutational amino acid substitutions observed in the viral variants, 13 potential epitopes were selected as subunit vaccine candidates. Despite mutational amino acid substitutions, most epitope sequences were predicted to retain immunogenicity without toxicity and host homology. Our RV approach using an pipeline may potentially reduce the time required for effective vaccine development and can be applicable for vaccine development for other pathogenic diseases as well.
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http://dx.doi.org/10.3390/v13050787DOI Listing
April 2021

Proteome-minimized outer membrane vesicles from as a generalized vaccine platform.

J Extracell Vesicles 2021 Feb 16;10(4):e12066. Epub 2021 Feb 16.

Department of Cellular, Computational and Integrative Biology (CIBIO) Laboratory of Synthetic and Structural Vaccinology University of Trento Trento Italy.

Because of their potent adjuvanticity, ease of manipulation and simplicity of production Gram-negative Outer Membrane Vesicles OMVs have the potential to become a highly effective vaccine platform. However, some optimization is required, including the reduction of the number of endogenous proteins, the increase of the loading capacity with respect to heterologous antigens, the enhancement of productivity in terms of number of vesicles per culture volume. In this work we describe the use of Synthetic Biology to create BL21(DE3)Δ60, a strain releasing OMVs (OMVs) deprived of 59 endogenous proteins. The strain produces large quantities of vesicles (> 40 mg/L under laboratory conditions), which can accommodate recombinant proteins to a level ranging from 5% to 30% of total OMV proteins. Moreover, also thanks to the absence of immune responses toward the inactivated endogenous proteins, OMVs decorated with heterologous antigens/epitopes elicit elevated antigens/epitopes-specific antibody titers and high frequencies of epitope-specific IFN-γ-producing CD8 T cells. Altogether, we believe that BL21(DE3)Δ60 have the potential to become a workhorse factory for novel OMV-based vaccines.
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http://dx.doi.org/10.1002/jev2.12066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886703PMC
February 2021

Improving sensitivity of single tube nested PCR to detect fastidious microorganisms.

Heliyon 2020 Jan 27;6(1):e03246. Epub 2020 Jan 27.

Palestine-Korea Biotechnology Center, Palestine Polytechnic University, P.O-Box 198, Hebron, Palestine.

Single Tube Nested PCR (ST-nPCR) is of value to clinical laboratories with limited settings for the detection of fastidious microorganisms. The detection sensitivity of ST-nPCR is dependent on ensuring minimal leftovers of outer primers during the second round of the reaction. In this work, we investigated various approaches to optimize the performance of outer primers, including decreasing outer primer concentrations; using antisense oligonucleotides to block outer primers; using chemically modified inner primers; and using Q5 Taq polymerase that lacks 5'-3' exonuclease and strand displacement capabilities. These solutions were tested on and , which are both fastidious intracellular bacteria that are difficult to diagnose. The best obtained result was by using Q5 Taq polymerase. A detection limit with a range between 0.1 and 1 ag was achieved, which corresponds to a range between 0.2 and 2 copies of the plasmid positive control. This level of sensitivity is comparable or even better than the sensitivity achieved by TaqMan probe based real-time PCR assays. The assay was validated using 70 veterinary clinical samples from small ruminant abortions and 10% of these samples gave positive results. In conclusion, sensitivity of ST-nPCR to detect fastidious microorganisms can be improved by using Taq polymerases that lacks 5'-3' exonuclease. The proposed assay is affordable and applicable to a wide range of fastidious pathogens and can be suitable for laboratories with limited settings.
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http://dx.doi.org/10.1016/j.heliyon.2020.e03246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002839PMC
January 2020

Identification of Cross-Protective Potential Antigens against Pathogenic spp. through Combining Pan-Genome Analysis with Reverse Vaccinology.

J Immunol Res 2018 9;2018:1474517. Epub 2018 Dec 9.

Palestine-Korea Biotechnology Center, Palestine Polytechnic University, Hebron, State of Palestine.

Brucellosis is a zoonotic infectious disease caused by bacteria of the genus . , , and are the most pathogenic species of this genus causing the majority of human and domestic animal brucellosis. There is a need to develop a safe and potent subunit vaccine to overcome the serious drawbacks of the live attenuated vaccines. The aim of this work was to discover antigen candidates conserved among the three pathogenic species. In this study, we employed a reverse vaccinology strategy to compute the core proteome of 90 completed genomes: 55 , 17 , and 18 . The core proteome was analyzed by a metasubcellular localization prediction pipeline to identify surface-associated proteins. The identified proteins were thoroughly analyzed using various tools to obtain the most potential protective antigens. The number of core proteins obtained from analyzing the 90 proteomes was 1939 proteins. The surface-associated proteins were 177. The number of potential antigens was 87; those with adhesion score ≥ 0.5 were considered antigen with "high potential," while those with a score of 0.4-0.5 were considered antigens with "intermediate potential." According to a cumulative score derived from protein antigenicity, density of MHC-I and MHC-II epitopes, MHC allele coverage, and B-cell epitope density scores, a final list of 34 potential antigens was obtained. Remarkably, most of the 34 proteins are associated with bacterial adhesion, invasion, evasion, and adaptation to the hostile intracellular environment of macrophages which is adjusted to deprive of required nutrients. Our results provide a manageable list of potential protective antigens for developing a potent vaccine against brucellosis. Moreover, our elaborated analysis can provide further insights into novel virulence factors. Our next step is to test some of these antigens using an appropriate antigen delivery system.
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http://dx.doi.org/10.1155/2018/1474517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304850PMC
April 2019

Accelerating Information Retrieval from Profile Hidden Markov Model Databases.

PLoS One 2016 22;11(11):e0166358. Epub 2016 Nov 22.

College of Information Technology and Computer Engineering, Palestine Polytechnic University, Hebron, Palestine.

Profile Hidden Markov Model (Profile-HMM) is an efficient statistical approach to represent protein families. Currently, several databases maintain valuable protein sequence information as profile-HMMs. There is an increasing interest to improve the efficiency of searching Profile-HMM databases to detect sequence-profile or profile-profile homology. However, most efforts to enhance searching efficiency have been focusing on improving the alignment algorithms. Although the performance of these algorithms is fairly acceptable, the growing size of these databases, as well as the increasing demand for using batch query searching approach, are strong motivations that call for further enhancement of information retrieval from profile-HMM databases. This work presents a heuristic method to accelerate the current profile-HMM homology searching approaches. The method works by cluster-based remodeling of the database to reduce the search space, rather than focusing on the alignment algorithms. Using different clustering techniques, 4284 TIGRFAMs profiles were clustered based on their similarities. A representative for each cluster was assigned. To enhance sensitivity, we proposed an extended step that allows overlapping among clusters. A validation benchmark of 6000 randomly selected protein sequences was used to query the clustered profiles. To evaluate the efficiency of our approach, speed and recall values were measured and compared with the sequential search approach. Using hierarchical, k-means, and connected component clustering techniques followed by the extended overlapping step, we obtained an average reduction in time of 41%, and an average recall of 96%. Our results demonstrate that representation of profile-HMMs using a clustering-based approach can significantly accelerate data retrieval from profile-HMM databases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0166358PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5119741PMC
June 2017

Identification of Brucella melitensis Rev.1 vaccine-strain genetic markers: Towards understanding the molecular mechanism behind virulence attenuation.

Vaccine 2016 09 29;34(41):4884-4891. Epub 2016 Aug 29.

Palestine-Korea Biotechnology Research Centre, Palestine Polytechnic University, P.O. Box 198, Hebron, Palestine. Electronic address:

Brucella melitensis Rev.1 is an avirulent strain that is widely used as a live vaccine to control brucellosis in small ruminants. Although an assembled draft version of Rev.1 genome has been available since 2009, this genome has not been investigated to characterize this important vaccine. In the present work, we used the draft genome of Rev.1 to perform a thorough genomic comparison and sequence analysis to identify and characterize the panel of its unique genetic markers. The draft genome of Rev.1 was compared with genome sequences of 36 different Brucella melitensis strains from the Brucella project of the Broad Institute of MIT and Harvard. The comparative analyses revealed 32 genetic alterations (30 SNPs, 1 single-bp insertion and 1 single-bp deletion) that are exclusively present in the Rev.1 genome. In silico analyses showed that 9 out of the 17 non-synonymous mutations are deleterious. Three ABC transporters are among the disrupted genes that can be linked to virulence attenuation. Out of the 32 mutations, 11 Rev.1 specific markers were selected to test their potential to discriminate Rev.1 using a bi-directional allele-specific PCR assay. Six markers were able to distinguish between Rev.1 and a set of control strains. We succeeded in identifying a panel of 32 genome-specific markers of the B. melitensis Rev.1 vaccine strain. Extensive in silico analysis showed that a considerable number of these mutations could severely affect the function of the associated genes. In addition, some of the discovered markers were able to discriminate Rev.1 strain from a group of control strains using practical PCR tests that can be applied in resource-limited settings.
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http://dx.doi.org/10.1016/j.vaccine.2016.08.059DOI Listing
September 2016

SslE elicits functional antibodies that impair in vitro mucinase activity and in vivo colonization by both intestinal and extraintestinal Escherichia coli strains.

PLoS Pathog 2014 May 8;10(5):e1004124. Epub 2014 May 8.

Novartis Vaccines and Diagnostics Srl, Siena, Italy.

SslE, the Secreted and surface-associated lipoprotein from Escherichia coli, has recently been associated to the M60-like extracellular zinc-metalloprotease sub-family which is implicated in glycan recognition and processing. SslE can be divided into two main variants and we recently proposed it as a potential vaccine candidate. By applying a number of in vitro bioassays and comparing wild type, knockout mutant and complemented strains, we have now demonstrated that SslE specifically contributes to degradation of mucin substrates, typically present in the intestine and bladder. Mutation of the zinc metallopeptidase motif of SslE dramatically impaired E. coli mucinase activity, confirming the specificity of the phenotype observed. Moreover, antibodies raised against variant I SslE, cloned from strain IHE3034 (SslEIHE3034), are able to inhibit translocation of E. coli strains expressing different variants through a mucin-based matrix, suggesting that SslE induces cross-reactive functional antibodies that affect the metallopeptidase activity. To test this hypothesis, we used well-established animal models and demonstrated that immunization with SslEIHE3034 significantly reduced gut, kidney and spleen colonization by strains producing variant II SslE and belonging to different pathotypes. Taken together, these data strongly support the importance of SslE in E. coli colonization of mucosal surfaces and reinforce the use of this antigen as a component of a broadly protective vaccine against pathogenic E. coli species.
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http://dx.doi.org/10.1371/journal.ppat.1004124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4014459PMC
May 2014

Developing a powerful in silico tool for the discovery of novel caspase-3 substrates: a preliminary screening of the human proteome.

BMC Bioinformatics 2012 Jan 23;13:14. Epub 2012 Jan 23.

Biotechnology Research Centre, Palestine Polytechnic University, Hebron, Palestine.

Background: Caspases are a family of cysteinyl proteases that regulate apoptosis and other biological processes. Caspase-3 is considered the central executioner member of this family with a wide range of substrates. Identification of caspase-3 cellular targets is crucial to gain further insights into the cellular mechanisms that have been implicated in various diseases including: cancer, neurodegenerative, and immunodeficiency diseases. To date, over 200 caspase-3 substrates have been identified experimentally. However, many are still awaiting discovery.

Results: Here, we describe a powerful bioinformatics tool that can predict the presence of caspase-3 cleavage sites in a given protein sequence using a Position-Specific Scoring Matrix (PSSM) approach. The present tool, which we call CAT3, was built using 227 confirmed caspase-3 substrates that were carefully extracted from the literature. Assessing prediction accuracy using 10 fold cross validation, our method shows AUC (area under the ROC curve) of 0.94, sensitivity of 88.83%, and specificity of 89.50%. The ability of CAT3 in predicting the precise cleavage site was demonstrated in comparison to existing state-of-the-art tools. In contrast to other tools which were trained on cleavage sites of various caspases as well as other similar proteases, CAT3 showed a significant decrease in the false positive rate. This cost effective and powerful feature makes CAT3 an ideal tool for high-throughput screening to identify novel caspase-3 substrates. The developed tool, CAT3, was used to screen 13,066 human proteins with assigned gene ontology terms. The analyses revealed the presence of many potential caspase-3 substrates that are not yet described. The majority of these proteins are involved in signal transduction, regulation of cell adhesion, cytoskeleton organization, integrity of the nucleus, and development of nerve cells.

Conclusions: CAT3 is a powerful tool that is a clear improvement over existing similar tools, especially in reducing the false positive rate. Human proteome screening, using CAT3, indicate the presence of a large number of possible caspase-3 substrates that exceed the anticipated figure. In addition to their involvement in various expected functions such as cytoskeleton organization, nuclear integrity and adhesion, a large number of the predicted substrates are remarkably associated with the development of nerve tissues.
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http://dx.doi.org/10.1186/1471-2105-13-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3324375PMC
January 2012

Manipulation of NK cytotoxicity by the IAP family member Livin.

Eur J Immunol 2007 Dec;37(12):3467-76

Department of Hematology, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.

Natural killer (NK) cells are part of the innate immune system, capable of killing tumor and virally infected cells. NK cells induce apoptosis in the target cell by either granule- or receptor-mediated pathways. A set of inhibitory and activation ligands governs NK cell activation. As transformed cells often attempt to evade NK cell killing, up-regulation of a potential anti-apoptotic factor should provide a survival advantage. The inhibitor of apoptosis protein (IAP) family can inhibit apoptosis induced by a variety of stimuli. We have previously described a new IAP family member, termed Livin, which has two splice variants (alpha and beta) with differential anti-apoptotic activities. In this study, we explore the ability of Livin to inhibit NK cell-induced killing. We demonstrate that Livin beta moderately protects against NK cell killing whereas Livin alpha augments killing. We show that Livin beta inhibition in Jurkat cells is apparent upon concomitant activation of an inhibitory signal, suggesting that Livin augments an extrinsic inhibitory signal rather than functioning as an independent inhibitory mechanism. Finally, we demonstrate that detection of both Livin isoforms in melanoma cells correlates with a low killing rate. To date, this is the first evidence that directly demonstrates the ability of IAP to protect against NK cell-induced apoptosis.
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http://dx.doi.org/10.1002/eji.200636600DOI Listing
December 2007

Multiple products derived from two CCL4 loci: high incidence of a new polymorphism in HIV+ patients.

J Immunol 2005 May;174(9):5655-64

Laboratory of Immunobiology for Research and Application to Diagnosis, Centre for Transfusion and Tissue Bank, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Barcelona, Spain.

Human CCL4/macrophage inflammatory protein (MIP)-1beta and CCL3/MIP-1alpha are two highly related molecules that belong to a cluster of inflammatory CC chemokines located in chromosome 17. CCL4 and CCL3 were formed by duplication of a common ancestral gene, generating the SCYA4 and SCYA3 genes which, in turn, present a variable number of additional non-allelic copies (SCYA4L and SCYA3L1). In this study, we show that both CCL4 loci (SCYA4 and SCYA4L) are expressed and alternatively generate spliced variants lacking the second exon. In addition, we found that the SCYA4L locus is polymorphic and displays a second allelic variant (hereinafter SCYA4L2) with a nucleotide change in the intron 2 acceptor splice site compared with the one described originally (hereinafter SCYA4L1). Therefore, the pattern of SCYA4L2 transcripts is completely different from that of SCYA4L1, since SCYA4L2 uses several new acceptor splice sites and generates nine new mRNAs. Furthermore, we analyzed the contribution of each locus (SCYA4 and SCYA4L1/L2) to total CCL4 expression in human CD8 T cells by RT-amplified fragment length polymorphism and real-time PCR, and we found that L2 homozygous individuals (L2L2) only express half the levels of CCL4 compared with L1L1 individuals. The analysis of transcripts from the SCYA4L locus showed a lower level in L2 homozygous compared with L1 homozygous individuals (12% vs 52% of total CCL4 transcripts). A possible clinical relevance of these CCL4 allelic variants was suggested by the higher frequency of the L2 allele in a group of HIV(+) individuals (n = 175) when compared with controls (n = 220, 28.6% vs 16.6% (p = 0.00016)).
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http://dx.doi.org/10.4049/jimmunol.174.9.5655DOI Listing
May 2005

Late-delayed cerebral involvement in systemic non-Hodgkin lymphoma: a second primary tumor or a tardy recurrence?

Cancer 2004 Oct;101(8):1843-9

Leslie and Michael Gaffin Center for Neuro-Oncology, Hadassah-Hebrew University Hospital, Jerusalem, Israel.

Background: Central nervous system involvement is a well recognized complication of systemic non-Hodgkin lymphoma. Most central nervous system recurrences occur within the first 2 years after the initial diagnosis and are considered to represent clonally related recurrence of systemic disease. The authors attempted to investigate the clonal relation between the late-delayed central nervous system involvement and the original systemic tumor.

Methods: The authors studied archival, formalin fixed, paraffin embedded tissue samples from 8 patients with isolated cerebral involvement diagnosed > 3 years after their initial presentation with aggressive, systemic, B-cell non-Hodgkin lymphoma. The rearranged immunoglobulin heavy-chain variable region genes (VH) from both sites were amplified by polymerase chain reaction and were sequenced when necessary.

Results: In three of five patients who had interpretable results, a distinct, monoclonal, VH family-specific band profile was obtained from the cerebral and systemic lymphoma. In the other two patients, a similar VH band pattern was observed and also was compared using direct sequencing, which demonstrated sequence differences between tumors from the two sites.

Conclusions: Clonal variance between the cerebral and systemic lymphoma in these patients suggested the possibility that some instances of late-delayed recurrence in the central nervous system represent a second, new B-cell lymphoma rather than a true recurrence of the original systemic tumor, a finding that may have significant clinical and biologic implications.
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http://dx.doi.org/10.1002/cncr.20575DOI Listing
October 2004

The inhibitor of apoptosis protein family (IAPs): an emerging therapeutic target in cancer.

Semin Cancer Biol 2004 Aug;14(4):231-43

Department of Hematology, Hadassah University Hospital, Ein-Karem, P.O.B. 12000, Jerusalem 91120, Israel.

Apoptosis is a crucial biological process that prevents uncontrolled cell proliferation and eliminates harmful cells. Resistance to apoptotic stimuli is a hallmark feature of various cancers. One of the mechanisms through which tumor cells are believed to acquire resistance to apoptosis is by overexpression of inhibitor of apoptosis proteins (IAPs). IAPs are a group of structurally related proteins that were initially identified in baculoviruses. Mammalian IAPs block apoptosis either by binding and inhibiting caspases or through caspase-independent mechanisms. This family of proteins has become increasingly prominent in the field of cancer biology. To date, overexpression of several IAPs has been detected in various cancers. This paper reviews the recent advances in the research of IAPs. The differential expression and the biological significance of each IAP in various cancer types will be discussed. Finally, we review the most recent advances in the research efforts aimed at using IAPs as potential targets for cancer therapy.
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http://dx.doi.org/10.1016/j.semcancer.2004.04.002DOI Listing
August 2004

Role of promoter methylation in regulation of the mammalian heparanase gene.

Oncogene 2003 Oct;22(49):7737-49

Department of Hematology, Hadassah- Hebrew University Medical Center, Jerusalem 91120, Israel.

Mammalian heparanase (endo-beta-glucuronidase) degrades heparan sulfate proteoglycans and is an important modulator of the extracellular matrix and associated factors. The enzyme is preferentially expressed in neoplastic tissues and contributes to tumour metastasis and angiogenesis. To investigate the epigenetic regulation of the heparanase locus, methylation-specific and bisulfite PCR were performed on a panel of 22 human cancer cell lines. Cytosine methylation of the heparanase promoter was associated with inactivation of the affected allele. Despite lack of sequence homology, extensively methylated CpG islands were found both in human choriocarcinoma (JAR) and rat glioma (C-6) cells which lack heparanase activity. Treatment of these cells with demethylating agents (5-azacytidine, 5-aza-2'-deoxycytidine) resulted in stable dose- and time-dependant promoter hypomethylation accompanied by reappearance of heparanase mRNA, protein and enzymatic activity. An inhibitor of histone deacetylase, Trichostatin A, failed to induce either of these effects. Upregulation of heparanase expression and activity by demethylating drugs was associated with a marked increase in lung colonization by pretreated C-6 rat glioma cells. The increased metastatic potential in vivo was inhibited in mice treated with laminaran sulfate, a potent inhibitor of heparanase activity. We propose a model wherein expression of mammalian heparanase gene is modulated by the interplay between trans-activating genetic and cis-inhibitory epigenetic elements in its promoter.
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http://dx.doi.org/10.1038/sj.onc.1207056DOI Listing
October 2003

Caspase-mediated cleavage converts Livin from an antiapoptotic to a proapoptotic factor: implications for drug-resistant melanoma.

Cancer Res 2003 Oct;63(19):6340-9

Department of Hematology, Hadassah University Hospital, Ein-Karem, Jerusalem 91120, Israel.

Inhibitor of apoptosis protein (IAP) is a family of intracellular proteins that plays an essential role in the regulation of apoptosis. Recently, we and others discovered a new member of this family, termed Livin. Many studies have focused on the inhibitory effect of IAPs on caspases. Here, we describe a novel regulatory mechanism by which Livin is cleaved by the caspases. Strikingly, the cleaved Livin, although containing intact baculovirus IAP repeat and RING domains, does not only lose its antiapoptotic function but also gains a proapoptotic effect. The cleavage is site specific at Asp-52 and is restricted to effector caspase-3 and -7. Most importantly, we demonstrate the role of Livin and this regulatory mechanism in the drug resistance of melanoma patients. Using primary cultures derived from melanoma patients, we found a correlation between Livin overexpression, in vitro drug resistance, and the patient's clinical response.
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October 2003

AU-differential display, reproducibility of a differential mRNA display targeted to AU motifs.

Methods Mol Biol 2003 ;226:225-36

Programa de Biotechnologia, Centro Nacional de Investigaciones Oncologicas, Madrid, Spain.

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http://dx.doi.org/10.1385/1-59259-384-4:225DOI Listing
November 2003

Identification of a KRAB-containing zinc finger protein, ZNF304, by AU-motif-directed display method and initial characterization in lymphocyte activation.

Biochem Biophys Res Commun 2002 May;293(3):1066-72

Immunology Unit, Germans Trias i Pujol University Hospital, Fundació per a la Recerca Biomèdica Germans Trias i Pujol, Crtra. del Canyet s/n, 08916 Badalona, Spain.

A novel human Krüppel-associated box (KRAB) type zinc finger protein encoding gene, ZNF304, was obtained by AU-motif-directed display and RACE. This gene, which contains a tandem AU motif in the 3' untranslated region, has an ORF 1977-bp long that codes for a putative 659 residue protein with an amino-terminal KRAB domain and 13 carboxyl-terminal C2H2 zinc finger units. The gene maps to chromosome 19q13.4, a region that contains the largest zinc finger cluster so far identified in the human genome. Structurally, ZNF304 is related to a family of repressor transcription factors. ZNF304 expression was higher in lymphoid tissues but it was also detected in the following tissues, ordered by abundance: thyroid, adrenal gland, prostate, pancreas, and skeletal muscle. Jurkat, U937, and THP1 cell lines showed a relatively low expression of ZNF304. By contrast, PBLs stimulated with PHA or PMA + ionomycin showed a biphasic expression with a sharp increase at 6 h. This induction was closely parallel to IFN-gamma expression and partially to IL-4 and IL-10. The tissue distribution and kinetics of induction suggest that ZNF304 may be involved in the regulation of lymphocyte activation.
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http://dx.doi.org/10.1016/S0006-291X(02)00344-3DOI Listing
May 2002