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 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.
Giannakakou
P
P
Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA.
Sackett
D L
DL
Ward
Y
Y
Webster
K R
KR
Blagosklonny
M V
MV
Fojo
T
T
D021581:Active Transport, Cell Nucleus; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D020409:Molecular Motor Proteins; D017239:Paclitaxel / Q000494:pharmacology; D011233:Precipitin Tests; D011485:Protein Binding; D014404:Tubulin / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014750:Vincristine / Q000494:pharmacology
C000606361:DCTN2 protein, human; D000072159:Dynactin Complex; D005231:Fatty Acids, Unsaturated; D008869:Microtubule-Associated Proteins; D020409:Molecular Motor Proteins; D014404:Tubulin; D016159:Tumor Suppressor Protein p53; D014750:Vincristine; D004398:Dyneins; D017239:Paclitaxel; C038753:leptomycin B