ArticleMolecular and cellular biology2006
Interferon-inducible protein IFIXalpha1 functions as a negative regulator of HDM2.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 45 citations in OpenAlex.
- APOBEC3G Is a p53-Dependent Restriction Factor in Respiratory Syncytial Virus Infection of Human Cells Included in the p53/Immune Axis.International journal of molecular sciences · 2023Article
- Non-synonymous, synonymous, and non-coding nucleotide variants contribute to recurrently altered biological processes during retinoblastoma progression.Genes, chromosomes & cancer · 2023Article
- The Wheel of p53 Helps to Drive the Immune System.International journal of molecular sciences · 2023Review
- Nuclear antiviral innate responses at the intersection of DNA sensing and DNA repair.Trends in microbiology · 2022Review
- Functions and roles of IFIX, a member of the human HIN-200 family, in human diseases.Molecular and cellular biochemistry · 2022Review
- Myeloid cell nuclear differentiation antigen controls the pathogen-stimulated type I interferon cascade in human monocytes by transcriptional regulation of IRF7.Nature communications · 2022Article
- PYHIN1 correlates with CD8+ T cells infiltration and confers good patient survival in oral cancer.Journal of dental sciences · 2022Article
- Interferon-inducible protein, IFIX, has tumor-suppressive effects in oral squamous cell carcinoma.Scientific reports · 2021Article
- Analysis of Immune-Related Signatures Related to CD4+ T Cell Infiltration With Gene Co-Expression Network in Pancreatic Adenocarcinoma.Frontiers in oncology · 2021Article
- Activation and Immune Regulation Mechanisms of PYHIN Family During Microbial Infection.Frontiers in microbiology · 2021Review
- Nuclear PYHIN proteins target the host transcription factor Sp1 thereby restricting HIV-1 in human macrophages and CD4+ T cells.PLoS pathogens · 2020Article
- PYHIN1 regulates pro-inflammatory cytokine induction rather than innate immune DNA sensing in airway epithelial cells.The Journal of biological chemistry · 2020Article
- A MicroRNA Network ControlsmBio · 2020Article
- PYHIN Proteins and HPV: Role in the Pathogenesis of Head and Neck Squamous Cell Carcinoma.Microorganisms · 2019Review
- Human Antiviral Protein IFIX Suppresses Viral Gene Expression during Herpes Simplex Virus 1 (HSV-1) Infection and Is Counteracted by Virus-induced Proteasomal Degradation.Molecular & cellular proteomics : MCP · 2017Article
- The functional interactome of PYHIN immune regulators reveals IFIX is a sensor of viral DNA.Molecular systems biology · 2015Article
- Article
- Global DNA hypomethylation coupled to repressive chromatin domain formation and gene silencing in breast cancer.Genome research · 2012Article
- Gingival tissue transcriptomes in experimental gingivitis.Journal of clinical periodontology · 2011Article
- Interferon-inducible protein 16: insight into the interaction with tumor suppressor p53.Structure (London, England : 1993) · 2011Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The 200-amino-acid repeat (HIN-200) gene family with the hematopoietic interferon (IFN)-inducible nuclear protein encodes highly homologous proteins involved in cell growth, differentiation, autoimmunity, and tumor suppression. IFIX is the newest member of the human HIN-200 family and is often downregulated in breast tumors and breast cancer cell lines. The expression of the longest isoform of IFIX gene products, IFIXalpha1, is associated with growth inhibition, suppression of transformation, and tumorigenesis. However, the mechanism underlying the tumor suppression activity of IFIXalpha1 is not well understood. Here, we show that IFIXalpha1 downregulates HDM2, a principal negative regulator of p53, at the posttranslational level. IFIXalpha1 destabilizes HDM2 protein and promotes its ubiquitination. The E3 ligase activity of HDM2 appears to be required for this IFIXalpha1 effect. Importantly, HDM2 downregulation is required for the IFIXalpha1-mediated increase of p53 protein levels, transcriptional activity, and nuclear localization, suggesting that IFIXalpha1 positively regulates p53 by acting as a negative regulator of HDM2. We found that IFIXalpha1 interacts with HDM2. Interestingly, the signature motif of the HIN-200 gene family, i.e., the 200-amino-acid HIN domain of IFIXalpha1, is sufficient not only for binding HDM2 but also for downregulating it, leading to p53 activation. Finally, we show that IFIX mediates HDM2 downregulation in an IFN-inducible system. Together, these results suggest that IFIXalpha1 functions as a tumor suppressor by repressing HDM2 function.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.