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


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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Fig. 1: p53 response elements in the human ARVCF gene.
Fig. 2: ARVCF expression is induced by the p53 family.
Fig. 3: p53-induced apoptosis is suppressed by ARVCF knockdown.
Fig. 4: Modulation of alternative splicing patterns by ARVCF knockdown.
Fig. 5: Correlation between ARVCF expression and prognosis among cancer patients.


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The computations were partially performed on the NIG supercomputer at ROIS National Institute of Genetics.


This work was supported by JSPS KAKENHI (grant numbers: 19K08372, 19K07645, 16K09285, and 16K07122) and Takeda Science Foundation.

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Correspondence to Masashi Idogawa or Takashi Tokino.

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Suzuki, N., Idogawa, M., Tange, S. et al. p53-induced ARVCF modulates the splicing landscape and supports the tumor suppressive function of p53. Oncogene 39, 2202–2211 (2020).

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