生物
癌症研究
RNA剪接
选择性拼接
抑制器
基因表达
拼接因子
平方毫米
细胞生物学
癌变
信使核糖核酸
癌症
基因
外显子
遗传学
抑癌基因
细胞凋亡
癌基因
基因敲除
突变
分子生物学
癌细胞
核糖核酸
作者
Natsumi Suzuki,Masashi Idogawa,Shoichiro Tange,Tomoko Ohashi,Yasushi Sasaki,Hiroshi Nakase,Takashi Tokino
出处
期刊:Oncogene
[Springer Nature]
日期:2019-12-11
卷期号:39 (10): 2202-2211
被引量:4
标识
DOI:10.1038/s41388-019-1133-7
摘要
p53 is one of the most important tumor suppressor genes, and the exploration of p53-target genes is important for elucidation of its functional mechanisms. In this study, we identified Armadillo Repeat gene deleted in Velo-Cardio-Facial syndrome (ARVCF) as a direct target of p53 through ChIP-sequencing analysis. Activated p53 protein was found to bind to two distinct sites in the ARVCF gene, resulting in induction of ARVCF expression at both the mRNA and protein levels. We revealed that the knockdown of ARVCF inhibited p53-induced apoptosis. Interestingly, ARVCF interacted with hnRNPH2, which is involved in pre-mRNA splicing, and ARVCF knockdown induced dynamic changes in alternative splicing patterns. These results suggest that p53-induced ARVCF indirectly, but not directly, regulates p53 target selectivity through splicing alterations of specific genes. Thus, we demonstrated that the induction of ARVCF expression contributed to the tumor suppressive function of p53. Recently, it has been reported that many tumors have thousands of alternative splicing events that are not detectable in normal samples. ARVCF may play a role in alternative splicing events in cancer and may provide clues to explore novel approaches for cancer diagnosis and therapy.
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