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p53活性在果蝇干细胞区室中被选择性激活。

p53 activity is selectively licensed in the Drosophila stem cell compartment.

作者信息

Wylie Annika, Lu Wan-Jin, D'Brot Alejandro, Buszczak Michael, Abrams John M

机构信息

Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, United States.

出版信息

Elife. 2014 Mar 11;3:e01530. doi: 10.7554/eLife.01530.

Abstract

Oncogenic stress provokes tumor suppression by p53 but the extent to which this regulatory axis is conserved remains unknown. Using a biosensor to visualize p53 action, we find that Drosophila p53 is selectively active in gonadal stem cells after exposure to stressors that destabilize the genome. Similar p53 activity occurred in hyperplastic growths that were triggered either by the Ras(V12) oncoprotein or by failed differentiation programs. In a model of transient sterility, p53 was required for the recovery of fertility after stress, and entry into the cell cycle was delayed in p53(-) stem cells. Together, these observations establish that the stem cell compartment of the Drosophila germline is selectively licensed for stress-induced activation of the p53 regulatory network. Furthermore, the findings uncover ancestral links between p53 and aberrant proliferation that are independent of DNA breaks and predate evolution of the ARF/Mdm2 axis. DOI: http://dx.doi.org/10.7554/eLife.01530.001.

摘要

致癌应激通过p53引发肿瘤抑制,但该调控轴的保守程度尚不清楚。利用一种生物传感器来可视化p53的作用,我们发现果蝇p53在暴露于使基因组不稳定的应激源后,在生殖干细胞中具有选择性活性。类似的p53活性也出现在由Ras(V12)癌蛋白或分化程序失败引发的增生性生长中。在一个短暂不育的模型中,应激后恢复生育能力需要p53,并且p53(-)干细胞进入细胞周期会延迟。这些观察结果共同表明,果蝇生殖系的干细胞区室被选择性地许可进行应激诱导的p53调控网络激活。此外,这些发现揭示了p53与异常增殖之间的祖先联系,这些联系独立于DNA断裂且早于ARF/Mdm2轴的进化。DOI: http://dx.doi.org/10.7554/eLife.01530.001

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0372/3949305/a5cd94e030df/elife01530f001.jpg

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