Cell cycle regulators interact with pathways that modulate microtubule stability in Saccharomyces cerevisiae.
Cell cycle regulators interact with pathways that modulate microtubule stability in Saccharomyces cerevisiae.
复制标题
细胞周期调节剂与调节酿酒酵母微管稳定性的途径相互作用。
DOI：
10.1128/ec.05215-11
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Eshel,Dan
中科院分区：
文献类型：
--
作者：
Shohat-Tal,Aya;Eshel,Dan
有丝分裂的完整性依赖于微管稳定性和动力学的严格调节。虽然已经积累了大量的信息对微管细胞骨架的调节，我们的知识涉及的具体途径仍然有限。在这里，我们设计了遗传筛选，以确定微管稳定性的调节因子，这些调节因子在野生型中是不稳定的，但在微管破坏条件下变得至关重要。我们发现，转录辅因子Swi 6p和激活剂Swi 4p，以及G2/M特异性细胞周期蛋白Clb 2 p，需要在微管不稳定的环境。Swi 6 p和Swi 4 p可以联合收割机形成转录复合物，称为SBF复合物（SBF代表Swi 4/6细胞周期盒[SCB]结合因子），其功能上与多细胞动物DP 1/2-E2 F复合物同源，并通过其调节的基因控制G1/S转变。我们表明，Swi 6p的微管稳定性的贡献可以是依赖或独立的SBF复合物。SBF依赖性途径需要下调SBF复合物水平，从而可能改变转录程序，有利于更大的微管稳定性。这一途径可以通过Fcp 1 p（一种在一般转录机制中的磷酸酶）的过表达或SWI 6等位基因的表达来触发，SWI 6等位基因与SBF控制的启动子的转录减少有关。SBF非依赖性途径由Swi 6p的组成性核等位基因激活。我们的研究结果介绍了新的作用，在微管稳定性的基因，其参与的过程中可能被掩盖在正常条件下，但仍然获得主导作用时，微管稳定性受到损害。
The integrity of mitosis is dependent upon strict regulation of microtubule stability and dynamics. Although much information has been accumulated on regulators of the microtubule cytoskeleton, our knowledge of the specific pathways involved is still limited. Here we designed genetic screens to identify regulators of microtubule stability that are dispensable in the wild type yet become essential under microtubule-disrupting conditions. We found that the transcriptional cofactor Swi6p and activator Swi4p, as well as the G2/M-specific cyclin Clb2p, are required in a microtubule-destabilizing environment. Swi6p and Swi4p can combine as a transcriptional complex, called the SBF complex (SBF for Swi4/6 cell cycle box [SCB]-binding factor) that is functionally homologous to the metazoan DP1/2-E2F complex and that controls the G1/S transition through the genes it regulates. We show that Swi6p's contribution to microtubule stability can be either dependent or independent of the SBF complex. The SBF-dependent pathway requires downregulation of SBF complex levels and may thereby reroute the transcriptional program in favor of greater microtubule stability. This pathway can be triggered by overexpression of Fcp1p, a phosphatase in the general transcription machinery, or by expression of an allele ofSWI6that is associated with reduced transcription from SBF-controlled promoters. The SBF-independent pathway is activated by a constitutively nuclear allele of Swi6p. Our results introduce novel roles in microtubule stability for genes whose participation in the process may be masked under normal conditions yet nonetheless acquire a dominant role when microtubule stability is compromised.