Jie Xu , Changkai Jia , Qiaocheng Qiu , Yuzhen Qin , Yuting Wang , Sijin Wu , Wei Li , Shengwei Ren , Yiqiang Wang
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引用次数: 0
Abstract
NLRP3 proteins mainly act as inflammasome core components in cytosol, but was sparsely recorded to translocate into nuclei in some conditions, such as in human simplex virus (HSV)-infected corneas, in SV40 T-Ag-immortalized human corneal epithelial cell (HCEC) line, or during differentiation of naïve T cells. This study was designed to define whether or how SV40 T-Ag transfection per se caused NLRP3 translocation. It was demonstrated that infection of primary human corneal epithelial cells with lentivirus coding for SV40 T-Ag induced NLRP3 proteins' translocation into nuclei. Pull-down of NLRP3-containing complexes in HCEC nuclear proteins followed by mass spectrometry revealed 285 nuclear proteins interacting with NLRP3 proteins. Clustering analysis of these proteins showed that “RNA binding”, “Nucleocytoplasmic transport” and “Viral carcinogenic pathway” were among the enriched molecular function terms or KEGG pathways. Structural modeling showed significant but differential affinities between NLRP3 proteins and histone subunits. Systemic Evolution of Ligands by EXponential enrichment (SELEX) was utilized to define DNA motifs potentially bound by NLRP3 proteins in vitro, and in-depth analysis of SELEXed motifs confirmed that the genes harboring those motifs were significantly associated with transcription and RNA processing. This study demonstrated that during the process of SV40 T-Ag-mediated corneal cell immortalization, NLRP3 proteins translocated into nuclei and behaved like a transcription factor. Besides confirming NLRP3 proteins’ novel functions in non-immune cells or tissues like cornea, these findings also shed light on the mechanisms of virus-mediated immortalization or viral induced carcinogenesis.
期刊介绍:
The primary goal of Experimental Eye Research is to publish original research papers on all aspects of experimental biology of the eye and ocular tissues that seek to define the mechanisms of normal function and/or disease. Studies of ocular tissues that encompass the disciplines of cell biology, developmental biology, genetics, molecular biology, physiology, biochemistry, biophysics, immunology or microbiology are most welcomed. Manuscripts that are purely clinical or in a surgical area of ophthalmology are not appropriate for submission to Experimental Eye Research and if received will be returned without review.