p53 is associated with cellular microtubules and is transported to the nucleus by dynein
p53 is associated with cellular microtubules and is transported to the nucleus by dynein
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DOI：
10.1038/35036335
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发表时间：
2000-10-01
影响因子：
21.3
通讯作者：
Fojo, T
中科院分区：
文献类型：
--
作者：
Giannakakou, P;Sackett, DL;Fojo, T
在这里，我们表明，p53蛋白在体内和体外与微管蛋白物理相关，它定位于细胞微管。在DNA损伤之前或在来普霉素B治疗之前用长春新碱或紫杉醇治疗减少了p53的核积累以及mdm2和p21的表达。过表达dynamitin或微量注射抗动力蛋白抗体DNA损伤前废除核积累的p53。我们的研究结果表明，p53沿着微管的运输是动力蛋白依赖的。p53的前25个氨基酸含有与微管结合所必需的残基。我们建议，功能微管和动力蛋白马达蛋白参与运输p53，并促进其在细胞核中的积累后，DNA损伤。
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.