The Barrier to Autointegration Factor: Interlocking Antiviral Defense with Genome Maintenance

Wiebe, Matthew S.; Jamin, Augusta

doi:10.1128/jvi.00178-16

Cited by 29 publications

(22 citation statements)

References 20 publications

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“…It was discovered due to its involvement in the integration of retroviral DNA ( 13 ). Regulation of BAF phosphorylation, mediated by cell or virus, regulates numerous cellular activities, including protein dimerization, its binding to DNA, and subcellular localization of the protein ( 14 – 16 ). Additionally, BAF participates in karyomitosis, karyon assembly, karyoplasm regulation and the DNA damage response ( 17 ).…”

Section: Discussionmentioning

confidence: 99%

Barrier‑to‑autointegration factor 1: A novel biomarker for gastric cancer

Fang

et al. 2018

Oncol Lett

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China is a country with a high incidence of gastric cancer (GC), where the GC incidence and the resultant mortality rates account for 50% of those worldwide. Surgical resection remains the primary treatment for GC. However, postoperative patients have a poor prognosis as the majority of patients present with metastases at the time of diagnosis. Therefore, the identification of novel treatment targets is required. The present study aimed to determine the effects of barrier-to-autointegration factor 1 (BANF1) on the clinical features and prognosis of GC, which may aid in discovering a novel tumor diagnostic biomarker and treatment target. The BANF1 gene expression profiles for normal and gastric tumor tissues were downloaded from the Gene Expression Omnibus GSE54129 data set to analyse the expression of BANF1 at the mRNA levels. Then, online survival analysis was performed using the GC database with the Kaplan-Meier Plotter () data. To examine the association between BANF1 and clinical features and prognosis, 132 postoperative GC pathological specimens were collected for immunohistochemical analyses. In the GSE54129 data sets, BANF1 expression at the mRNA level was significantly higher in the tumor tissue compared with that in the normal tissue. The same result was obtained in following the immunohistochemical analyses. In addition, BANF1 expression was associated with the patient age, tumor differentiation and infiltration depth. The survival time of BANF1 high-expression patients was shorter compared with that of the low-expression patients, and tumor differentiation status and tumor node metastasis stage were independent prognostic factors of the overall survival of patients with GC. The results of the present study suggest that BANF1 is associated with the clinical features and prognosis of GC. It may be a novel indicator of tumor prognosis and a potential therapeutic target for GC.

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Section: Discussionmentioning

confidence: 99%

Barrier‑to‑autointegration factor 1: A novel biomarker for gastric cancer

Fang

et al. 2018

Oncol Lett

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“…We performed a genome-wide CRISPR-Cas9 screen in BV2 microglial cells and evaluated for genes that, when edited, resulted in increased cell surface expression of Bst2 (tetherin), a well-described ISG with antiviral activity against multiple enveloped RNA and retroviruses (9,10). One of our top "hits" was Barrier-to-autointegration factor 1 (Banf1), a small (10 kDa) conserved DNA-binding protein with homeostatic functions in mitosis, nuclear assembly, and the DNA damage response (11,12) that also can recognize foreign DNA and prevent chromosomal integration (13) or genome replication (14). Banf1 is expressed normally in the inner nuclear membrane but can relocalize to the cytoplasm depending on the stage of cell cycle and age of the cell (15).…”

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confidence: 99%

Barrier-to-Autointegration Factor 1 Protects against a Basal cGAS-STING Response

Qian

Bambousková

et al. 2020

mBio

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Although the pathogen recognition receptor pathways that activate cell-intrinsic antiviral responses are well delineated, less is known about how the host regulates this response to prevent sustained signaling and possible immune-mediated damage. Using a genome-wide CRISPR-Cas9 screening approach to identify host factors that modulate interferon-stimulated gene (ISG) expression, we identified the DNA binding protein Barrier-to-autointegration factor 1 (Banf1), a previously described inhibitor of retrovirus integration, as a modulator of basal cell-intrinsic immunity. Ablation of Banf1 by gene editing resulted in chromatin activation near host defense genes with associated increased expression of ISGs, including Oas2, Rsad2 (viperin), Ifit1, and ISG15. The phenotype in Banf1-deficient cells occurred through a cGAS-, STING-, and IRF3-dependent signaling axis, was associated with reduced infection of RNA and DNA viruses, and was reversed in Banf1 complemented cells. Confocal microscopy and biochemical studies revealed that a loss of Banf1 expression resulted in higher level of cytosolic double-stranded DNA at baseline. Our study identifies an undescribed role for Banf1 in regulating the levels of cytoplasmic DNA and cGAS-dependent ISG homeostasis and suggests possible therapeutic directions for promoting or inhibiting cell-intrinsic innate immune responses. IMPORTANCE Although the interferon (IFN) signaling pathway is a key host mechanism to restrict infection of a diverse range of viral pathogens, its unrestrained activity either at baseline or in the context of an immune response can result in host cell damage and injury. Here, we used a genome-wide CRISPR-Cas9 screen and identified the DNA binding protein Barrier-to-autointegration factor 1 (Banf1) as a modulator of basal cell-intrinsic immunity. A loss of Banf1 expression resulted in higher level of cytosolic double-stranded DNA at baseline, which triggered IFN-stimulated gene expression via a cGAS-STING-IRF3 axis that did not require type I IFN or STAT1 signaling. Our experiments define a regulatory network in which Banf1 limits basal inflammation by preventing self DNA accumulation in the cytosol.

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“…Members of the BAF complex family have a variety of functions associated with the maintenance of the intact cellular genome, which are reported to play essential roles in carcinogenesis and cancer progression. 6,7 As an important part of the lamina, BANF1 encodes a highly conserved BAF protein consisting of 89 amino acids and binding to double-stranded DNA with high-affinity. BANF1 is located at the core of chromatin and participate in completing the nuclear membrane reformation, indicating that BANF1 plays an important role in cell mitosis.…”

Section: Discussionmentioning

confidence: 99%

<p>Expression and Prognostic Significance of BANF1 in Triple-Negative Breast Cancer</p>

Zhang¹

2020

CMAR

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Aim: To investigate the expression of barrier-to-autointegration factor 1 (BANF1) and its prognostic significance in triple-negative breast cancer (TNBC). Methods: BANF1 immunohistochemical detection was performed in 60 TNBC specimens and 30 normal control tissues. Real-time PCR was performed to assess the expression of BANF1 gene in TNBC tissues and their correlations with proliferation and metastasis. Kaplan-Meier survival analysis was used to assess the effect of BANF1 expression on the relapse-free survival (RFS) of TNBC patients. Univariable and multivariable Cox proportional hazards regression model analysis was used to confirm independent prognostic factors. Results: Expression of BANF1 in TNBC was significantly higher than that of the normal control group (p<0.001), and it was related to the status of lymph node metastasis and TNM staging (p<0.05), and not related to age and tumor size (p>0.05). BANF1 expression has a positive correlation with MKI67 and MTA1 expression (p<0.01). Univariable analysis showed that expression of BANF1, the status of lymph node metastasis and TNM stage were related to the relapse-free survival (RSF) of TNBC patients (p<0.001, p=0.001, p=0.013, respectively). Multivariable Cox regression indicated that the status of lymph node metastasis was an independent prognostic factor for TNBC patients (p<0.001). The survival curve suggested that the survival times for TNBC patients with high BANF1 expression have no difference compared with that for the low-expression patients (p>0.05). Conclusion: Expression of BANF1 may play a role in the occurrence and development of TNBC. Lymph node metastasis was the only independent prognostic factor predicts a poor prognosis.

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The Barrier to Autointegration Factor: Interlocking Antiviral Defense with Genome Maintenance

Cited by 29 publications

References 20 publications

Barrier‑to‑autointegration factor 1: A novel biomarker for gastric cancer

Barrier‑to‑autointegration factor 1: A novel biomarker for gastric cancer

Barrier-to-Autointegration Factor 1 Protects against a Basal cGAS-STING Response

<p>Expression and Prognostic Significance of BANF1 in Triple-Negative Breast Cancer</p>

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