A ubiquitous β-tubulin disrupts microtubule assembly and inhibits cell proliferation

被引:84
作者
Bhattacharya, R [1 ]
Cabral, F [1 ]
机构
[1] Univ Texas, Sch Med, Dept Integrat Biol & Pharmacol, Houston, TX 77030 USA
关键词
D O I
10.1091/mbc.E04-01-0060
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Vertebrate tubulin is encoded by a multigene family that produces distinct gene products, or isotypes, of both the alpha- and beta-tubulin subunits. The isotype sequences are conserved across species supporting the hypothesis that different isotypes subserve different functions. To date, however, most studies have demonstrated that tubulin isotypes are freely interchangeable and coassemble into all classes of microtubules. We now report that, in contrast to other isotypes, overexpression of a mouse class V beta-tubulin cDNA in mammalian cells produces a strong, dose-dependent disruption of microtubule organization, increased microtubule fragmentation, and a concomitant reduction in cellular microtubule polymer levels. These changes also disrupt mitotic spindle assembly and block cell proliferation. Consistent with diminished microtubule assembly, there is an increased tolerance for the microtubule stabilizing drug, paclitaxel, which is able to reverse many of the effects of class V beta-tubulin overexpression. Moreover, transfected cells selected in paclitaxel exhibit increased expression of class V beta-tubulin, indicating that this isotype is responsible for the drug resistance. The results show that class V beta-tubulin is functionally distinct from other tubulin isotypes and imparts unique properties on the microtubules into which it incorporates.
引用
收藏
页码:3123 / 3131
页数:9
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