Bu W, Su L K
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, TX 77030, USA.
Oncogene. 2001 May 31;20(25):3185-92. doi: 10.1038/sj.onc.1204429.
The EB1 family proteins are highly conserved microtubule-associated proteins. The EB1 protein in yeast has been shown to play an important role in regulating microtubule dynamics and chromosome segregation. Human EB1 family proteins include EB1, RP1 and EBF3. Although EB1 and RP1 have been shown to associate with microtubules, the subcellular localization of endogenous EBF3 had not been characterized. The function of human EB1 family proteins was also not clear. We therefore investigated the cellular localization of EBF3 and the regulation of microtubule organization by EB1 family proteins. As do EB1 and RP1, EBF3 was found to colocalize with microtubules, preferentially at their plus ends, throughout the cell cycle. Moreover, there was a very strong EBF3 signal at the centrosome in interphase cells and at the spindle poles in mitotic cells. When EB1 family proteins were overexpressed, they associated with the entire microtubule cytoskeleton. In addition, EB1 and EBF3 induced microtubule bundling in some cells overexpressing these proteins. These microtubule bundles were more resistant to nocodazole and were more acetylated than regular microtubules. Our results demonstrate for the first time that human EB1 family proteins could regulate microtubule assembly and stability.
EB1家族蛋白是高度保守的微管相关蛋白。酵母中的EB1蛋白已被证明在调节微管动力学和染色体分离中起重要作用。人类EB1家族蛋白包括EB1、RP1和EBF3。尽管EB1和RP1已被证明与微管相关，但内源性EBF3的亚细胞定位尚未得到表征。人类EB1家族蛋白的功能也不清楚。因此，我们研究了EBF3的细胞定位以及EB1家族蛋白对微管组织的调节。与EB1和RP1一样，在整个细胞周期中，EBF3都与微管共定位，优先位于其正端。此外，在间期细胞的中心体和有丝分裂细胞的纺锤极有非常强的EBF3信号。当EB1家族蛋白过表达时，它们与整个微管细胞骨架相关。此外，EB1和EBF3在一些过表达这些蛋白的细胞中诱导微管成束。这些微管束比正常微管对诺考达唑更具抗性，且乙酰化程度更高。我们的结果首次证明人类EB1家族蛋白可以调节微管组装和稳定性。
