Journal Article

p53-induced ARVCF modulates the splicing landscape and supports the tumor suppressive function of p53

Ohashi Tomoko, Tange Shoichiro, Sasaki Yasushi, Suzuki Natsumi, Nakase Hiroshi, Tokino Takashi, Idogawa Masashi

2020

Overview

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.

• Publisher: Nature Publishing Group
• Subject: Alternative splicing / Apoptosis / Gene expression / Genes / mRNA / p53 Protein / Sequence analysis / Tumor suppressor genes / Tumors