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Regulation of ATR-dependent pathways by the FHA domain containing protein SNIP1

Oncogene volume 26, pages 4523–4530 (2007)Cite this article

Abstract

The forkhead associated (FHA) domain-containing protein Smad nuclear interacting protein 1 (SNIP1) has multiple cellular functions, including the ability to interact with DNA-binding transcription factors and transcriptional coactivators. Moreover, we have demonstrated previously that SNIP1 regulates cyclin D1 expression and promoter activity. Here, we identify a new function for SNIP1 as a regulator of ATR checkpoint kinase-dependent pathways in human U-2 OS osteosarcoma cells: SNIP1 is required for p53 induction in response to ultraviolet light treatment and selectively regulates the phosphorylation of known ATR target proteins, including p53, Chk1 and the histone variant H2AX. These activities are independent of its ability to regulate cyclin D1 expression. Significantly, SNIP1 is also required for ATR-dependent functions of the human p14ARF tumour suppressor, including its ability to modulate the activity of the RelA(p65) NF-κB subunit. This, together with its other described functions, suggests that SNIP1 could have an important role during tumorigenesis and cancer therapy.

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Acknowledgements

We are grateful to Dr Anita Roberts for her help, assistance and encouragement to investigate SNIP1. She will be greatly missed. We thank Dr Kirsteen Campbell who prepared the SNIP1 monoclonal antibodies used in this study, Katie Schumm for characterization of the cyclin D1 siRNA, Dr Kostya Panov for providing gel filtration protein samples and Dr John Rouse for helpful discussions. KCR was funded by the Association of International Cancer Research (AICR) and SR and CPB are funded by a programme grant from Cancer Research UK (C1443/A5435). Additional funding was received from the Royal Society.

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  1. K C Roche

    Present address: 3Current address: Genome Stability Laboratory, Department of Biochemistry, University of Galway, Galway, Ireland.,

  2. K C Roche, S Rocha and C P Bracken: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, Scotland, UK

    K C Roche, S Rocha, C P Bracken & N D Perkins

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  1. K C Roche
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Correspondence to N D Perkins.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Roche, K., Rocha, S., Bracken, C. et al. Regulation of ATR-dependent pathways by the FHA domain containing protein SNIP1. Oncogene 26, 4523–4530 (2007). https://doi.org/10.1038/sj.onc.1210233

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