P53 is transported into the nucleus via an Hsf1-dependent nuclear localization mechanism.
P53 is transported into the nucleus via an Hsf1-dependent nuclear localization mechanism.
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DOI：
10.1002/mc.20713
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发表时间：
2011-02
影响因子：
4.6
通讯作者：
Martinez, Jesse D.
中科院分区：
文献类型：
--
作者：
Li, Qiang;Martinez, Jesse D.
p53功能的丧失可以通过破坏其定位于细胞核的能力而发生。之前，我们通过表征一组缺乏将p53导入细胞核的能力的突变细胞系，发现p53的核易位似乎与SV40 t抗原（SV40TAg）的核易位在机制上有所不同。在这里，我们通过体内和体外核定位检测p53和SV40TAg的核输入来扩展这项工作。我们发现秋水仙碱破坏微管聚合可以抑制p53的核定位，但对SV40TAg没有作用。我们还首次表明，热休克转录因子（Hsf1）是细胞微管网络建立和p53核定位所必需的。相反，SV40TAg不与聚合微管相互作用，这表明它通过另一种机制被转运到细胞核中。有趣的是，缺乏Hsf1表达和通过siRNA抑制Hsf1也使细胞对紫杉醇的细胞毒性作用更具抵抗力。因此，Hsf1活性的丧失不仅抑制了p53功能，还导致靶向微管的药物杀伤敏感性降低。
Loss of p53 function can occur through disruption of its ability to localize to the nucleus. Previously we showed through characterization a set of mutant cell lines that lacked the ability to import p53 into the nucleus that nuclear translocation of p53 appeared to be mechanistically different from that of the SV40 T-antigen (SV40TAg). Here we extend that work by examining nuclear importation of p53 and SV40TAg using both in vivo and in vitro assays for nuclear localization. We show that disruption of microtubule polymerization using colchicine suppresses nuclear localization of p53 but not of SV40TAg. We also show, for the first time, that the heat shock transcription factor (Hsf1), is required for establishment of the microtubule network in cells and for nuclear localization of p53. In contrast, SV40TAg does not interact with polymerized microtubules suggesting that it is transported into the nucleus through an alternative mechanism. Interestingly, lacking of Hsf1 expression and suppressing Hsf1 by siRNA also made cells more resistant to the cytotoxic effects of paclitaxel. Hence, loss of Hsf1 activity not only suppressed p53 function, but also led to reduced sensitivity to killing by drugs that target microtubules.
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影响因子：
4.8
作者：
Akakura, S;Yoshida, M;Horinouchi, S
通讯作者：
Horinouchi, S
影响因子：
3.6
作者：
Salmand, Pierre A.;Jungas, Thomas;Christians, Elisabeth S.
通讯作者：
Christians, Elisabeth S.
DOI：
10.1073/pnas.92.10.4407
发表时间：
1995-05-09
影响因子：
11.1
作者：
MOLL, UM;LAQUAGLIA, M;RIOU, G
通讯作者：
RIOU, G
影响因子：
8
作者：
Li, Q.;Falsey, R. R.;Martinez, J. D.
通讯作者：
Martinez, J. D.
影响因子：
21.3
作者：
Giannakakou, P;Sackett, DL;Fojo, T
通讯作者：
Fojo, T