Abstract
We have previously shown that the transcription factor AP-1 regulates the expression of genes which allow neoplastically transformed rat fibroblasts to become invasive. Searches for further AP-1 target genes led to the identification of a gene encoding a novel rat kelch family member, named kelch related protein 1 (Krp1). Kelch family members are characterized by a series of repeats at their carboxyl terminus and a BTB/POZ domain near their amino terminus. Rat Krp1 has a primarily cytoplasmic localization, and a small fraction appears to accumulate and co-localize with F-actin at membrane ruffle-like structures in the tips of pseudopodia. Overexpression of Krp1 in transformed rat fibroblasts led to the formation of dramatically elongated pseudopodia, while expression of truncated Krp1 polypeptides resulted in a reduction in the length of pseudopodia. We propose that the transformation-specific expression of Krp1 is required for pseudopod elongation, which are structures that are required for cell motility and invasion.
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Acknowledgements
We would like to thank Prof. JA Wyke and Drs MC Frame and G Stapleton for critical reading of the manuscript. We also thank P McHardy for assistance with microscopy. Thanks to E Schieble of the Beatson Institute for the tubulin monoclonal antibody. We gratefully acknowledge the Cancer Research Campaign for their financial support.
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Spence, H., Johnston, I., Ewart, K. et al. Krp1, a novel kelch related protein that is involved in pseudopod elongation in transformed cells. Oncogene 19, 1266–1276 (2000). https://doi.org/10.1038/sj.onc.1203433
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DOI: https://doi.org/10.1038/sj.onc.1203433
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