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PMID: 11025661 Published · ppublish English Journal Article

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

Nature cell biology ·Vol. 2 ·No. 10 ·2000-10-00 ·Pages 709-17

Giannakakou P, Sackett DL, Ward Y, Webster KR, Blagosklonny MV, Fojo T

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.

MeSH Terms
Active Transport, Cell Nucleus Dynactin Complex Dyneins/metabolism Fatty Acids, Unsaturated/pharmacology Fluorescent Antibody Technique Humans Microtubule-Associated Proteins/metabolism Microtubules/metabolism Molecular Motor Proteins Paclitaxel/pharmacology Precipitin Tests Protein Binding Tubulin/metabolism Tumor Cells, Cultured Tumor Suppressor Protein p53/metabolism Vincristine/pharmacology
Chemicals
DCTN2 protein, human Dynactin Complex Fatty Acids, Unsaturated Microtubule-Associated Proteins Molecular Motor Proteins Tubulin Tumor Suppressor Protein p53 Vincristine Dyneins Paclitaxel leptomycin B
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Giannakakou P
Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA.
Sackett D L
Ward Y
Webster K R
Blagosklonny M V
Fojo T
Article Info
Journal
Nature cell biology
Abbr.
Nat Cell Biol
ISSN
1465-7392
Published
2000-10-00
Pages
709-17
Language
English
Region
England
NLM ID
100890575
Subset
IM
Corrections
CommentIn
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