Néstor-Guillermo Progeria Syndrome: a biochemical insight into Barrier-to-Autointegration Factor 1, alanine 12 threonine mutation

Paquet, Nicolas; Box, Joseph; Ashton, Nicholas W.; Suraweera, Amila; Croft, Laura V.; Urquhart, Aaron; Bolderson, Emma; Zhang, Shudong; O’Byrne, Kenneth J.; Richard, Derek J.

doi:10.1186/s12867-014-0027-z

Cited by 41 publications

(48 citation statements)

References 26 publications

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“…Activation of BANF1 may inhibit skin inflammation in psoriatic lesions by inactivation of S100A9 and c-Jun, but it may also promote keratinocyte proliferation ( 5 ). A coding mutation of the BANF1 alanine-12 to threonine was reported to be associated with BANF1-protein instability and abnormalities of the caryotheca, which has been confirmed as the hereditary fundamental of Néstor-Guillermo Progeria syndrome (NGPS) ( 25 ). The disruption of the interaction between Prelamin A and BAF may be the cause of NGPS ( 26 ).…”

Section: Discussionmentioning

confidence: 96%

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: 96%

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

Fang

et al. 2018

Oncol Lett

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“…1 ), and altered subcellular distribution of emerin (see Box 1 ) ( Cabanillas et al, 2011 ; Puente et al, 2011 ). The A12T mutation also weakens the binding of BAF to DNA, which is crucial for its many roles in the cell, suggesting that this deficiency contributes to the cellular phenotype observed in NGPS ( Paquet et al, 2014 ). NGPS shares many clinical features with HGPS ( Table 1 ), but, for unknown reasons, lacks cardiovascular defects, which likely contributes to the longer lifespan of NGPS patients ( Cabanillas et al, 2011 ).…”

Section: A Classification System For Human Progeroid Syndromesmentioning

confidence: 99%

Hallmarks of progeroid syndromes: lessons from mice and reprogrammed cells

Carrero

López-Otı́n

2016

Disease Models &Amp; Mechanisms

122

139

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Ageing is a process that inevitably affects most living organisms and involves the accumulation of macromolecular damage, genomic instability and loss of heterochromatin. Together, these alterations lead to a decline in stem cell function and to a reduced capability to regenerate tissue. In recent years, several genetic pathways and biochemical mechanisms that contribute to physiological ageing have been described, but further research is needed to better characterize this complex biological process. Because premature ageing (progeroid) syndromes, including progeria, mimic many of the characteristics of human ageing, research into these conditions has proven to be very useful not only to identify the underlying causal mechanisms and identify treatments for these pathologies, but also for the study of physiological ageing. In this Review, we summarize the main cellular and animal models used in progeria research, with an emphasis on patient-derived induced pluripotent stem cell models, and define a series of molecular and cellular hallmarks that characterize progeroid syndromes and parallel physiological ageing. Finally, we describe the therapeutic strategies being investigated for the treatment of progeroid syndromes, and their main limitations.

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“…BAF has also been implicated in human disease; a point mutation within the BAF coding region has been identified in two patients presenting with a hereditary progeroid disease called NestorGuillermo progeria syndrome (23). The molecular underpinnings of these defects are likely multifactorial (24), as BAF functions during mitosis and other processes integral to maintaining genomic integrity (45). In addition to these cellular functions, BAF is also capable of strongly inhibiting vaccinia virus DNA replication (25,26) and intermediate transcription (27).…”

mentioning

confidence: 99%

Deletion of the Vaccinia Virus B1 Kinase Reveals Essential Functions of This Enzyme Complemented Partly by the Homologous Cellular Kinase VRK2

Olson

Rico

Wang

et al. 2017

J Virol

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The vaccinia virus B1 kinase is highly conserved among poxviruses and is essential for the viral life cycle. B1 exhibits a remarkable degree of similarity to vaccinia virus-related kinases (VRKs), a family of cellular kinases, suggesting that the viral enzyme has evolved to mimic VRK activity. Indeed, B1 and VRKs have been demonstrated to target a shared substrate, the DNA binding protein BAF, elucidating a signaling pathway important for both mitosis and the antiviral response. In this study, we further characterize the role of B1 during vaccinia infection to gain novel insights into its regulation and integration with cellular signaling pathways. We begin by describing the construction and characterization of the first B1 deletion virus (vvΔB1) produced using a complementing cell line expressing the viral kinase. Examination of vvΔB1 revealed that B1 is critical for the production of infectious virions in various cell types and is sufficient for BAF phosphorylation. Interestingly, the severity of the defect in DNA replication following the loss of B1 varied between cell types, leading us to posit that cellular VRKs partly complement for the absence of B1 in some cell lines. Using cell lines devoid of either VRK1 or VRK2, we tested this hypothesis and discovered that VRK2 expression facilitates DNA replication and allows later stages of the viral life cycle to proceed in the absence of B1. Finally, we present evidence that the impact of VRK2 on vaccinia virus is largely independent of BAF phosphorylation. These data support a model in which B1 and VRK2 share additional substrates important for the replication of cytoplasmic poxviruses.IMPORTANCE Viral mimicry of cellular signaling modulators provides clear evidence that the pathogen targets an important host pathway during infection. Poxviruses employ numerous viral homologs of cellular proteins, the study of which have yielded insights into signaling pathways used by both virus and cells alike. The vaccinia virus B1 protein is a homolog of cellular vaccinia virus-related kinases (VRKs) and is needed for viral DNA replication and likely other stages of the viral life cycle. However, much remains to be learned about how B1 and VRKs overlap functionally. This study utilizes new tools, including a B1 deletion virus and VRK knockout cells, to further characterize the functional links between the viral and cellular enzymes. As a result, we have discovered that B1 and VRK2 target a common set of substrates vital to productive infection of this large cytoplasmic DNA virus.

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Néstor-Guillermo Progeria Syndrome: a biochemical insight into Barrier-to-Autointegration Factor 1, alanine 12 threonine mutation

Cited by 41 publications

References 26 publications

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

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

Hallmarks of progeroid syndromes: lessons from mice and reprogrammed cells

Deletion of the Vaccinia Virus B1 Kinase Reveals Essential Functions of This Enzyme Complemented Partly by the Homologous Cellular Kinase VRK2

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