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  • Original Article
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Nucleolin is involved in interferon regulatory factor-2-dependent transcriptional activation

Abstract

We have previously shown that interferon regulatory factor-2 (IRF-2) is acetylated in a cell growth-dependent manner, which enables it to contribute to the transcription of cell growth-regulated promoters. To clarify the function of acetylation of IRF-2, we investigated the proteins that associate with acetylated IRF-2. In 293T cells, the transfection of p300/CBP-associated factor (PCAF) enhanced the acetylation of IRF-2. In cells transfected with both IRF-2 and PCAF, IRF-2 associated with endogenous nucleolin, while in contrast, minimal association was observed when IRF-2 was transfected with a PCAF histone acetyl transferase (HAT) deletion mutant. In a pull-down experiment using stable transfectants, acetylation-defective mutant IRF-2 (IRF-2K75R) recruited nucleolin to a much lesser extent than wild-type IRF-2, suggesting that nucleolin preferentially associates with acetylated IRF-2. Nucleolin in the presence of PCAF enhanced IRF-2-dependent H4 promoter activity in NIH3T3 cells. Nucleolin knock-down using siRNA reduced the IRF-2/PCAF-mediated promoter activity. Chromatin immunoprecipitation analysis indicated that PCAF transfection increased nucleolin binding to IRF-2 bound to the H4 promoter. We conclude that nucleolin is recruited to acetylated IRF-2, thereby contributing to gene regulation crucial for the control of cell growth.

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Acknowledgements

This work was supported by the Japan Society for Promotion of Sciences and the Ministry of Education, Science, Sports and Culture and the Japan Health Sciences International Foundation. We thank Dr Y Nakatani for providing plasmids, Dr K Sakai and Dr M Kasai for technical advices, Dr K Kamemura, Dr A Ito, Dr Y Murakami and Dr I Hamaguchi for useful discussions, and Dr A Fuse and Dr Y Uehera for general support.

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Correspondence to A Masumi.

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Masumi, A., Fukazawa, H., Shimazu, T. et al. Nucleolin is involved in interferon regulatory factor-2-dependent transcriptional activation. Oncogene 25, 5113–5124 (2006). https://doi.org/10.1038/sj.onc.1209522

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