Abstract
Twist is basic helix-loop-helix transcription factor that binds to E-boxes in gene promoters. Twist possesses an oncogenic function by interfering with the tumor suppressor function of p53. Using a membrane pull-down assay, we found that Twist directly interacts with p53 and that this interaction underlies the inhibitory effects on p53 target gene expression. Twist interacted with the DNA-binding domain of p53 and suppressed the DNA-binding activity of p53. Transcriptional activation of the p21 promoter by p53 was significantly repressed by the expression of Twist. On the other hand, p53 interacted with the N-terminal domain of Twist and repressed Twist-dependent YB-1 promoter activity. Importantly, we found that p53-dependent growth suppression was canceled by the expression of either Twist or YB-1. Thus, our data suggest that Twist inhibits p53 function via a direct interaction with p53.
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Acknowledgements
This work was supported in part by the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Mext), Kakenhi (13218132 and 17590257), the Kobayashi Institute for Innovative Cancer Chemotherapy and a grant-in-aid for Cancer Research from the Fukuoka Cancer Society, Japan. We thank Satoko Takazaki and Yukiko Yoshiura for their technical assistance.
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Shiota, M., Izumi, H., Onitsuka, T. et al. Twist and p53 reciprocally regulate target genes via direct interaction. Oncogene 27, 5543–5553 (2008). https://doi.org/10.1038/onc.2008.176
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DOI: https://doi.org/10.1038/onc.2008.176
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