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Regulation of SV40 large T-antigen stability by reversible acetylation

Oncogene volume 25, pages 7391–7400 (2006)Cite this article

A Corrigendum to this article was published on 17 July 2014

Abstract

Reversible acetylation on protein lysine residues has been shown to regulate the function of both nuclear proteins such as histones and p53 and cytoplasmic proteins such as α-tubulin. To identify novel acetylated proteins, we purified several proteins by the affinity to an anti-acetylated-lysine antibody from cells treated with trichostatin A (TSA). Among the proteins identified, here we report acetylation of the SV40 large T antigen (T-Ag). The acetylation site was determined to be lysine-697, which is located adjacent to the C-terminal Cdc4 phospho-degron (CPD). Overexpression of the CBP acetyltransferase acetylated T-Ag, whereas HDAC1, HDAC3 and SIRT1 bound and deacetylated T-Ag. The acetylation and deacetylation occurred independently of p53, a binding partner of T-Ag, but the acetylation was enhanced in the presence of p53. T-Ag in the cells treated with TSA and NA or the acetylation mimic mutant (K697Q) became unstable in COS-7 cells, suggesting that acetylation regulates stability of T-Ag. Indeed, NIH3T3 cells stably expressing K697Q showed decreased anchorage-independent growth compared with those expressing wild type or the K697R mutant. These results demonstrate that acetylation destabilizes T-Ag and regulates the transforming activity of T-Ag in NIH3T3 cells.

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Acknowledgements

We thank Tso-Pang Yao for providing the CBP, SIRT1-5 and p53, Xiang-Jiao Yang for the PCAF, Saadi Khochbin for the HA-TIP60. We are grateful for the support of RIKEN BSI's Research Resources Center for the LC-MS/MS analysis. This work was supported in part by the Program for the Promotion of Fundamental studies in Health Science of the National Institute of Biomedical Innovation (NIBIO), and a Grant-in-Aid for Scientific Research on Priority Area ‘Cancer’ from The Ministry of Education, Culture, Sports, Science and Technology, Japan.

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Authors and Affiliations

  1. Chemical Genetics Laboratory, RIKEN, Hirosawa 2-1, Wako, Saitama, Japan

    T Shimazu & M Yoshida

  2. Department of Biotechnology, The University of Tokyo, Bunkyo-ku, Tokyo, Japan

    T Shimazu, S Horinouchi & M Yoshida

  3. Advanced Life Science Institute Inc., Maruyamadai, Wako, Saitama, Japan

    Y Komatsu

  4. Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan

    K I Nakayama

  5. CREST Research Project, Japan Science and Technology Agency, Saitama, Japan

    K I Nakayama & M Yoshida

  6. Department of Bioactive Molecules, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo, Japan

    H Fukazawa

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  1. T Shimazu
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  2. Y Komatsu
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  3. K I Nakayama
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  4. H Fukazawa
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Correspondence to M Yoshida.

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Shimazu, T., Komatsu, Y., Nakayama, K. et al. Regulation of SV40 large T-antigen stability by reversible acetylation. Oncogene 25, 7391–7400 (2006). https://doi.org/10.1038/sj.onc.1209731

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