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人类髓系白血病细胞中细胞周期阻滞反应的蛋白质组学分析

Proteomic analysis of the response to cell cycle arrests in human myeloid leukemia cells.

作者信息

Ly Tony, Endo Aki, Lamond Angus I

机构信息

Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, United Kingdom.

出版信息

Elife. 2015 Jan 2;4:e04534. doi: 10.7554/eLife.04534.

Abstract

Previously, we analyzed protein abundance changes across a 'minimally perturbed' cell cycle by using centrifugal elutriation to differentially enrich distinct cell cycle phases in human NB4 cells (Ly et al., 2014). In this study, we compare data from elutriated cells with NB4 cells arrested at comparable phases using serum starvation, hydroxyurea, or RO-3306. While elutriated and arrested cells have similar patterns of DNA content and cyclin expression, a large fraction of the proteome changes detected in arrested cells are found to reflect arrest-specific responses (i.e., starvation, DNA damage, CDK1 inhibition), rather than physiological cell cycle regulation. For example, we show most cells arrested in G2 by CDK1 inhibition express abnormally high levels of replication and origin licensing factors and are likely poised for genome re-replication. The protein data are available in the Encyclopedia of Proteome Dynamics (

摘要

此前,我们通过使用离心淘析法对人NB4细胞中不同的细胞周期阶段进行差异富集,分析了“微扰”细胞周期中的蛋白质丰度变化(Ly等人,2014年)。在本研究中,我们将淘析细胞的数据与使用血清饥饿、羟基脲或RO-3306在可比阶段停滞的NB4细胞的数据进行了比较。虽然淘析细胞和停滞细胞具有相似的DNA含量和细胞周期蛋白表达模式,但发现在停滞细胞中检测到的大部分蛋白质组变化反映的是停滞特异性反应(即饥饿、DNA损伤、CDK1抑制),而非生理性细胞周期调控。例如,我们发现,大多数因CDK1抑制而停滞在G2期的细胞表达异常高水平的复制和起始许可因子,并且可能准备进行基因组重新复制。蛋白质数据可在《蛋白质组动力学百科全书》中获取(

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff67/4383314/314074a318a6/elife04534f001.jpg

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