Functional Interfaces, Biological Pathways, and Regulations of Interferon-Related DNA Damage Resistance Signature (IRDS) Genes
Language English Country Switzerland Media electronic
Document type Journal Article, Research Support, Non-U.S. Gov't, Review
Grant support
MAB/3/2017
Fundacja na rzecz Nauki Polskiej
2020/36/C/NZ2/00108
The National Science Centre (Narodowe Centrum Nauki; Krakow, Poland)
PubMed
33922087
PubMed Central
PMC8143464
DOI
10.3390/biom11050622
PII: biom11050622
Knihovny.cz E-resources
- Keywords
- ATP, DNA, DNA damage, IRDS genes, RNA, chemotherapy and radiotherapy, functional site, interferon, protein interfaces, receptors, resistance, upstream regulator, viruses,
- MeSH
- Adaptor Proteins, Signal Transducing physiology MeSH
- Transcriptional Activation MeSH
- Drug Resistance, Neoplasm genetics physiology MeSH
- RNA, Double-Stranded MeSH
- Interferon Regulatory Factor-7 MeSH
- Interferons metabolism physiology MeSH
- Intracellular Signaling Peptides and Proteins MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- DNA Damage genetics physiology MeSH
- RNA-Binding Proteins MeSH
- Signal Transduction MeSH
- STAT1 Transcription Factor MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Adaptor Proteins, Signal Transducing MeSH
- RNA, Double-Stranded MeSH
- IFIT1 protein, human MeSH Browser
- IFIT3 protein, human MeSH Browser
- Interferon Regulatory Factor-7 MeSH
- Interferons MeSH
- Intracellular Signaling Peptides and Proteins MeSH
- IRF7 protein, human MeSH Browser
- RNA-Binding Proteins MeSH
- STAT1 protein, human MeSH Browser
- STAT1 Transcription Factor MeSH
Interferon (IFN)-related DNA damage resistant signature (IRDS) genes are a subgroup of interferon-stimulated genes (ISGs) found upregulated in different cancer types, which promotes resistance to DNA damaging chemotherapy and radiotherapy. Along with briefly discussing IFNs and signalling in this review, we highlighted how different IRDS genes are affected by viruses. On the contrary, different strategies adopted to suppress a set of IRDS genes (STAT1, IRF7, OAS family, and BST2) to induce (chemo- and radiotherapy) sensitivity were deliberated. Significant biological pathways that comprise these genes were classified, along with their frequently associated genes (IFIT1/3, IFITM1, IRF7, ISG15, MX1/2 and OAS1/3/L). Major upstream regulators from the IRDS genes were identified, and different IFN types regulating these genes were outlined. Functional interfaces of IRDS proteins with DNA/RNA/ATP/GTP/NADP biomolecules featured a well-defined pharmacophore model for STAT1/IRF7-dsDNA and OAS1/OAS3/IFIH1-dsRNA complexes, as well as for the genes binding to GDP or NADP+. The Lys amino acid was found commonly interacting with the ATP phosphate group from OAS1/EIF2AK2/IFIH1 genes. Considering the premise that targeting IRDS genes mediated resistance offers an efficient strategy to resensitize tumour cells and enhances the outcome of anti-cancer treatment, this review can add some novel insights to the field.
Department of Medical Biosciences Building 6M Umeå University 901 85 Umeå Sweden
Institute of Genetics and Molecular Medicine University of Edinburgh Edinburgh EH4 2XR UK
RECAMO Masaryk Memorial Cancer Institute Zlutykopec 7 65653 Brno Czech Republic
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