机体的细胞并非是一成不变的,它们可以随时转变其形状,但这种变化往往是一种危险信号,如良性细胞就可能转变成癌变细胞。如果能够找到导致细胞发生这一转变的机制,将使科学家更好地了解许多不同的细胞——如干细胞转变成癌细胞的过程。了解这种转变机制也有助于科学家找到治疗一些疾病的方法。
Jeffrey Laney通过对酿酒酵母(Saccharomyces cerevisae)研究发现,酿酒酵母在完成自我受精(self-fertilize)的过程中,其细胞形状由“a”字形转变成为“α(alpha)”形状。
在酿酒酵母细胞内,存在一种调节蛋白,该调节蛋白能结合到细胞内某个基因上形成一个“帽”结构,调控基因的表达,从而实现细胞在不同形状之间的转变。
虽然该课题组研究的这类基因在人类基因组中并不存在,但是研究人员认为,这种通过调控基因的开启和关闭来实现细胞不同形状的改变,应该在所有细胞中普遍存在。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature Cell Biology 11, 1481 - 1486 (2009) 15 November 2009 | doi:10.1038/ncb1997
A ubiquitin-selective AAA-ATPase mediates transcriptional switching by remodelling a repressor–promoter DNA complex
Alexander J. Wilcox1 & Jeffrey D. Laney1
Switches between different phenotypes and their underlying states of gene transcription occur as cells respond to intrinsic developmental cues or adapt to changing environmental conditions. Post-translational modification of the master regulatory transcription factors that define the initial phenotype is a common strategy to direct such transitions. Emerging evidence indicates that the modification of key transcription factors by the small polypeptide ubiquitin has a central role in many of these transitions1, 2. However, the molecular mechanisms by which ubiquitylation regulates the switching of promoters between active and inactive states are largely unknown. Ubiquitylation of the yeast transcriptional repressor 2 is necessary to evoke the transition between mating-types3, and here we dissect the impact of this modification on 2 dynamics at its target promoters. Ubiquitylation of 2 does not alter DNA occupancy by depleting the existing pool of the transcription factor, despite its well-characterized function in directing repressor turnover. Rather, 2 ubiquitylation has a direct role in the rapid removal of the repressor from its DNA targets. This disassembly of 2 from DNA depends on the ubiquitin-selective AAA-ATPase Cdc48. Our findings expand the functional targets of Cdc48 to include active transcriptional regulatory complexes in the nucleus. These data reveal an ubiquitin-dependent extraction pathway for dismantling transcription factor–DNA complexes and provide an archetype for the regulation of transcriptional switching events by ubiquitylation.
Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Box G-L2, Providence, RI 02912, USA.