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Actin: a novel interaction partner of WT1 influencing its cell dynamic properties

Oncogene volume 29, pages 1085–1092 (2010)Cite this article

Abstract

The Wilms’ tumour suppressor, WT1, is a zinc finger protein with key roles in normal development of the genitourinary system and tumourigenesis. Mutations or deletion of WT1 result in a spectrum of developmental disorders and susceptibility to Wilms’ tumour in children. Ectopic expression of Wt1 associated with oncogenic functions has been observed in a large number of malignancies, including haematological and solid cancers. Although Wt1 is predominantly a nuclear protein in normal tissues, it is mostly cytoplasmic in the majority of Wt1-expressing tumours. Actin was identified in this study as a new WT1 interaction partner both in the nucleus and in the cytoplasm. We confirmed this interaction both in vitro and in vivo and started to explore its functional significance. Perturbation of the actin cytoskeleton moved Wt1 off the polysome fraction in the cytoplasm, cancelled its nucleo-cytoplasmic shuttling and altered Wt1 DNA- and RNA-binding abilities. These data have implications for Wt1 functions in relation to RNA metabolism and response to cytoskeletal alterations in cancer cells. Thus, our findings could shed more light on the functions of both these proteins and possibly pave way for the development of new cancer therapies.

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Acknowledgements

We thank Drs J Caceres and S Guil for their useful advice and GFP-hnRNP A1 and GFP-SF2 expressing constructs and anti-hnRNP A1 antibody. We also thank Mr Nick Tomczyk from the Chemistry Department at the University of Edinburgh for carrying out MALDI-TOF analysis. This study was funded by a core grant from the MRC and an EU Marie Curie Fellowship to TD.

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Authors and Affiliations

  1. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK

    T Dudnakova, L Spraggon, J Slight & N Hastie

  2. Institute of Human Genetics, International Centre for Life, University of Newcastle, Central Parkway, Newcastle, UK

    L Spraggon

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  1. T Dudnakova
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  2. L Spraggon
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  3. J Slight
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  4. N Hastie
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Correspondence to N Hastie.

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Dudnakova, T., Spraggon, L., Slight, J. et al. Actin: a novel interaction partner of WT1 influencing its cell dynamic properties. Oncogene 29, 1085–1092 (2010). https://doi.org/10.1038/onc.2009.444

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