Inhibition of post-transcriptional steps in ribosome biogenesis confers cytoprotection against chemotherapeutic agents in a p53-dependent manner.
Inhibition of post-transcriptional steps in ribosome biogenesis confers cytoprotection against chemotherapeutic agents in a p53-dependent manner.
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抑制核糖体生物发生后的转录后步骤以p53依赖性方式对化学治疗剂赋予细胞保护作用。
DOI：
10.1038/s41598-017-09002-w
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发表时间：
2017-08-22
影响因子：
4.6
通讯作者：
Pestov DG
中科院分区：
文献类型：
--
作者：
Sapio RT;Nezdyur AN;Krevetski M;Anikin L;Manna VJ;Minkovsky N;Pestov DG
The p53-mediated nucleolar stress response associated with inhibition of ribosomal RNA transcription was previously shown to potentiate killing of tumor cells. Here, we asked whether targeting of ribosome biogenesis can be used as the basis for selective p53-dependent cytoprotection of nonmalignant cells. Temporary functional inactivation of the 60S ribosome assembly factor Bop1 in a 3T3 cell model markedly increased cell recovery after exposure to camptothecin or methotrexate. This was due, at least in part, to reversible pausing of the cell cycle preventing S phase associated DNA damage. Similar cytoprotective effects were observed after transient shRNA-mediated silencing of Rps19, but not several other tested ribosomal proteins, indicating distinct cellular responses to the inhibition of different steps in ribosome biogenesis. By temporarily inactivating Bop1 function, we further demonstrate selective killing of p53-deficient cells with camptothecin while sparing isogenic p53-positive cells. Thus, combining cytotoxic treatments with inhibition of select post-transcriptional steps of ribosome biogenesis holds potential for therapeutic targeting of cells that have lost p53.
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影响因子：
7.3
作者：
Henras, Anthony K.;Plisson-Chastang, Celia;O'Donohue, Marie-Francoise;Chakraborty, Anirban;Gleizes, Pierre-Emmanuel
通讯作者：
Gleizes, Pierre-Emmanuel
影响因子：
20.3
作者：
Choesmel, Valerie;Bacqueville, Daniel;Gleizes, Pierre-Emmanuel
通讯作者：
Gleizes, Pierre-Emmanuel
影响因子：
20.3
作者：
Flygare, Johan;Aspesi, Anna;Ellis, Steven R.
通讯作者：
Ellis, Steven R.
DOI：
10.1073/pnas.1418845112
发表时间：
2015-02-17
影响因子：
11.1
作者：
Fortier, Simon;MacRae, Tara;Sauvageau, Guy
通讯作者：
Sauvageau, Guy
影响因子：
2.3
作者：
Idol, Rachel A.;Robledo, Sara;Mason, Philip J.
通讯作者：
Mason, Philip J.