Transcription factor MIZ-1 is regulated via microtubule association

被引:82
作者
Ziegelbauer, J
Shan, B
Yager, D
Larabell, C
Hoffmann, B
Tjian, R [1 ]
机构
[1] Univ Calif Berkeley, Howard Hughes Med Inst, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
[2] Tularik Inc, S San Francisco, CA 94080 USA
[3] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA
[4] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA
关键词
D O I
10.1016/S1097-2765(01)00313-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A synthetic drug, T113242, activates low-density lipoprotein receptor (LDLR) transcription in the presence of sterols. T113242 also covalently binds to beta -tubulin and induces microtubule depolymerization. The myc-interacting zinc finger protein (MIZ-1) associates with microtubules, can bind directly to the LDLR promoter, and can activate LDLR transcription. MIZ-1 also binds to the promoter and activates transcription of other T113242-induced genes such as alpha (2) integrin. Soft X-ray, indirect immunofluorescence, and green fluorescent protein time-lapse microscopy reveal that MIZ-1 is largely cytoplasmic but accumulates in the nuclei of HepG2 cells upon treatment with T113242. Thus, MIZ-1 appears to be regulated by association with microtubules and may activate gene transcription in response to changes in the cytoskeleton.
引用
收藏
页码:339 / 349
页数:11
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