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Adenovirus early region 1A protein binds to mammalian SUG1-a regulatory component of the proteasome

Oncogene volume 18, pages 449–458 (1999)Cite this article

Abstract

Adenovirus early region 1A (Ad E1A) is a multifunctional protein which is essential for adenovirus-mediated transformation and oncogenesis. Whilst E1A is generally considered to exert its influence on recipient cells through regulation of transcription it also increases the level of cellular p53 by increasing the protein half-life. With this in view, we have investigated the relationship of Ad E1A to the proteasome, which is normally responsible for degradation of p53. Here we have shown that both Ad5 and Ad12 E1A 12S and 13S proteins can be co-immunoprecipitated with proteasomes and that the larger Ad12 E1A protein binds strongly to at least three components of the 26S but not 20S proteasome. One of these interacting species has been identified as mammalian SUG1, a proteasome regulatory component which also plays a role in the cell as a mediator of transcription. In vitro assays have demonstrated a direct interaction between Ad12 E1A 13S protein and mouse SUG1. Following infection of human cells with Ad5 wt and Ad5 mutants with lesions in the E1A gene it has been shown that human SUG1 can be co-immunoprecipitated with full-length E1A and with E1A carrying a deletion in conserved region 1 which is the region considered to be responsible for increased expression of p53. We have concluded therefore that Ad E1A binds strongly to SUG1 but that this interaction is not responsible for inhibition of proteasome activity. This is consistent with the observation that purified Ad12 E1A inhibits the activity of the purified 20S but not 26S proteasomes. We have also demonstrated that SUG1 can be co-immunoprecipitated with SV40 T and therefore we suggest that this may represent a common interaction of transforming proteins of DNA tumour viruses.

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Acknowledgements

We are grateful to Jutta Reidlinger and Rachael Murray (Department of Biochemistry, University of Bristol) for provision of purified proteasomes and Dr Sally Roberts (Institute for Cancer Studies, University of Birmingham) for provision of HPV1 E4-GST fusion protein and antibodies against HPV1 E4. We thank Nicola Waldron for excellent secretarial assistance and Susan Williams for photography. This work was funded by the Cancer Research Campaign, the Lister Institute and the Wellcome Trust. PHG is a Cancer Research Campaign Gibb Fellow.

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Authors and Affiliations

  1. CRC Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, B15 2TA, UK

    Roger JA Grand, Andrew S Turnell, Anne E Milner, Susan M Rookes & Phillip H Gallimore

  2. Howard Hughes Medical Institute and the Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, 2120S, Maryland, USA

    Wenlan Wang

  3. Department of Biochemistry, University Walk, University of Bristol, Bristol, BS8 1TD, UK

    Grant GF Mason & A Jennifer Rivett

  4. Department of Oncology, University of Western Ontario, London, N6A 4L6, Ontario, Canada

    Joe S Mymryk

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Grand, R., Turnell, A., Mason, G. et al. Adenovirus early region 1A protein binds to mammalian SUG1-a regulatory component of the proteasome. Oncogene 18, 449–458 (1999). https://doi.org/10.1038/sj.onc.1202304

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