Discovery and characterization of a novel splice variant of the p53 tumor suppressor gene in a human T cell leukemia cellline

人类 T 细胞白血病细胞系中 p53 肿瘤抑制基因新型剪接变体的发现和表征

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作者:Xiaomei Li, Yingshou Lei, Yang Yu, Yaqian Zhang, Wenfeng Zhang, Han Shen, Changli Tao, Fenglin Wu, Shulin Huang, Hongwei Shao

Abstract

Alternative splicing produces multiple mRNA variants of TP53 which have diverse biologic functions. In this study, we identified a novel splice variant of TP53 lacking a 200 nt portion of exon 4 (p53ΔE4p) from a human leukemia T cell line. No protein product of p53ΔE4p was identifiable by western blot; however, forced expression of the variant in HEK-293T cells expressing wild-type p53 could inhibit cell proliferation and promote cell death. Interestingly, this novel variant also significantly enhances the expression of reporter genes. Moreover, transcriptome analysis showed that genes related to DNA binding and regulation of transcription by RNA polymerase II function were significantly upregulated following p53ΔE4p transfection, suggesting a role for this variant in the regulation of gene expression.

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