Abstract
Here we show that p53 protein is physically associated with tubulin in vivo and in vitro, and that it localizes to cellular microtubules. Treatment with vincristine or paclitaxel before DNA-damage or before leptomycin B treatment reduces nuclear accumulation of p53 and expression of mdm2 and p21. Overexpression of dynamitin or microinjection of anti-dynein antibody before DNA damage abrogates nuclear accumulation of p53. Our results indicate that transport of p53 along microtubules is dynein-dependent. The first 25 amino acids of p53 contain the residues that are essential for binding to microtubules. We propose that functional microtubules and the dynein motor protein participate in transport of p53 and facilitate its accumulation in the nucleus after DNA damage.
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Acknowledgements
We thank H. Gray and U. Roongta for help with expression and purification of His–p53 fusion protein. We are grateful to M. Clarke and C. Harris for providing full-length wild-type p53 and p53 (Δ342–end) plasmids, respectively. We also thank R. Vallee for providing the dynamitin plasmid, and L. Neckers for providing Leptomycin B. We are indebted to R. Klausner for insightful discussion.
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Giannakakou, P., Sackett, D., Ward, Y. et al. p53 is associated with cellular microtubules and is transported to the nucleus by dynein. Nat Cell Biol 2, 709–717 (2000). https://doi.org/10.1038/35036335
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DOI: https://doi.org/10.1038/35036335
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