p53 is associated with cellular microtubules and is transported to the nucleus by dynein

Here we show that p53 protein is physically associated with tubulin in vivo and in vitro, and that it localizes to cellular microtubules. Treatment wi th vincristine or paclitaxel before DNA-damage or before leptomycin B treat ment reduces nuclear accumulation of p53 and expression of mdm2 and p21. Ov erexpression 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 amin o acids of p53 contain the residues that are essential for binding to micro tubules. We propose that functional microtubules and the dynein motor prote in participate in transport of p53 and facilitate its accumulation in the n ucleus after DNA damage.