Ask about this productRelated genes to: ZNF579 Blocking Peptide
- Gene:
- ZNF579 NIH gene
- Name:
- zinc finger protein 579
- Previous symbol:
- -
- Synonyms:
- FLJ35453
- Chromosome:
- 19q13.42
- Locus Type:
- gene with protein product
- Date approved:
- 2004-02-15
- Date modifiied:
- 2015-08-26
Related products to: ZNF579 Blocking Peptide
Related articles to: ZNF579 Blocking Peptide
- Studying viral-host protein-protein interactions can facilitate the discovery of therapies for viral infection. We use high-throughput yeast two-hybrid experiments and mass spectrometry to generate a comprehensive SARS-CoV-2-human protein-protein interactome network consisting of 739 high-confidence binary and co-complex interactions, validating 218 known SARS-CoV-2 host factors and revealing 361 novel ones. Our results show the highest overlap of interaction partners between published datasets and of genes differentially expressed in samples from COVID-19 patients. We identify an interaction between the viral protein ORF3a and the human transcription factor ZNF579, illustrating a direct viral impact on host transcription. We perform network-based screens of >2,900 FDA-approved or investigational drugs and identify 23 with significant network proximity to SARS-CoV-2 host factors. One of these drugs, carvedilol, shows clinical benefits for COVID-19 patients in an electronic health records analysis and antiviral properties in a human lung cell line infected with SARS-CoV-2. Our study demonstrates the value of network systems biology to understand human-virus interactions and provides hits for further research on COVID-19 therapeutics. - Source: PubMed
Publication date: 2022/10/10
Zhou YadiLiu YuanGupta ShagunParamo Mauricio IHou YuanMao ChengshengLuo YuanJudd JuliusWierbowski ShayneBertolotti MartaNerkar MrigankaJehi LaraDrayman NirNicolaescu VladGula HaleyTay SavaşRandall GlennWang PeihuiLis John TFeschotte CédricErzurum Serpil CCheng FeixiongYu Haiyuan - Physical interactions between viral and host proteins are responsible for almost all aspects of the viral life cycle and the host's immune response. Studying viral-host protein-protein interactions is thus crucial for identifying strategies for treatment and prevention of viral infection. Here, we use high-throughput yeast two-hybrid and affinity purification followed by mass spectrometry to generate a comprehensive SARS-CoV-2-human protein-protein interactome network consisting of both binary and co-complex interactions. We report a total of 739 high-confidence interactions, showing the highest overlap of interaction partners among published datasets as well as the highest overlap with genes differentially expressed in samples (such as upper airway and bronchial epithelial cells) from patients with SARS-CoV-2 infection. Showcasing the utility of our network, we describe a novel interaction between the viral accessory protein ORF3a and the host zinc finger transcription factor ZNF579 to illustrate a SARS-CoV-2 factor mediating a direct impact on host transcription. Leveraging our interactome, we performed network-based drug screens for over 2,900 FDA-approved/investigational drugs and obtained a curated list of 23 drugs that had significant network proximities to SARS-CoV-2 host factors, one of which, carvedilol, showed promising antiviral properties. We performed electronic health record-based validation using two independent large-scale, longitudinal COVID-19 patient databases and found that carvedilol usage was associated with a significantly lowered probability (17%-20%, < 0.001) of obtaining a SARS-CoV-2 positive test after adjusting various confounding factors. Carvedilol additionally showed anti-viral activity against SARS-CoV-2 in a human lung epithelial cell line [half maximal effective concentration (EC ) value of 4.1 µM], suggesting a mechanism for its beneficial effect in COVID-19. Our study demonstrates the value of large-scale network systems biology approaches for extracting biological insight from complex biological processes. - Source: PubMed
Publication date: 2022/06/07
Zhou YadiLiu YuanGupta ShagunParamo Mauricio IHou YuanMao ChengshengLuo YuanJudd JuliusWierbowski ShayneBertolotti MartaNerkar MrigankaJehi LaraDrayman NirNicolaescu VladGula HaleyTay SavaşRandall GlennLis John TFeschotte CédricErzurum Serpil CCheng FeixiongYu Haiyuan - 5-Lipoxygenase (5-LO) is the initial enzyme in the biosynthesis of leukotrienes, which are mediators involved in pathophysiological conditions such as asthma and certain cancer types. Knowledge of proteins involved in 5-LO pathway regulation, including gene regulatory proteins, is needed to evaluate all options for therapeutic intervention in these diseases. Here, we present a mass spectrometric screening of ALOX5 promoter-interacting proteins, obtained by DNA pulldown and label-free quantitative mass spectrometry. Protein preparations from myeloid and B-lymphocytic cell lines were screened for promoter DNA interactors. Through statistical analysis, 66 proteins were identified as specific ALOX5 promotor binding proteins. Among those, the 15 most likely candidates for a prominent role in ALOX5 gene regulation are the known ALOX5 interactors Sp1 and Sp3, the related factor Sp2, two Krüppel-like factors (KLF13 and KLF16) and six other zinc finger proteins (MAZ, PRDM10, VEZF1, ZBTB7A, ZNF281 and ZNF579). Intriguingly, we also identified two helicases (BLM and DHX36) and the proteins hnRNPD and hnRNPK, which are, together with the protein MAZ, known to interact with DNA G-quadruplex structures. As G-quadruplexes are implicated in gene regulation, spectroscopic and antibody-based methods were used to confirm their presence within the GC-rich sequence of the ALOX5 promoter. In summary, we have systematically characterized the interactome of the ALOX5 promoter, identifying several zinc finger proteins as novel potential ALOX5 gene regulators. Further, we have shown that the ALOX5 promoter can form DNA G-quadruplex structures, which may play a functional role in ALOX5 gene regulation. - Source: PubMed
Publication date: 2020/03/13
Schlag KatharinaSteinhilber DieterKaras MichaelSorg Bernd L