6月15日,，Science雜志報(bào)道,，p53蛋白對(duì)刺激反應(yīng)的不同動(dòng)力學(xué)可導(dǎo)致不同的細(xì)胞命運(yùn)。細(xì)胞傳遞信息的分子信號(hào)通路常顯示出復(fù)雜的動(dòng)力學(xué)模式,。腫瘤抑制因子p53的動(dòng)力學(xué)行為就可隨刺激的不同而變化,。在面對(duì)DNA雙鏈的斷裂時(shí)，它的反應(yīng)表現(xiàn)為一系列重復(fù)的脈沖式變化,。
利用一個(gè)計(jì)算機(jī)模型,，研究者確定了一套精確定時(shí)的給藥方案，可以將脈沖式p53反應(yīng)變?yōu)槌掷m(xù)性p53反應(yīng),。這導(dǎo)致一系列不同的下游基因的表達(dá),，并且改變細(xì)胞命運(yùn)。經(jīng)歷脈沖式p53反應(yīng)的細(xì)胞可從DNA損傷中恢復(fù),，而經(jīng)歷持續(xù)性p53反應(yīng)的細(xì)胞則往往發(fā)生細(xì)胞衰老,。這些研究結(jié)果顯示，蛋白反應(yīng)動(dòng)力學(xué)是信號(hào)通路的重要部分,，直接影響著細(xì)胞命運(yùn)的決定,。
研究者認(rèn)為,，本研究的意義可能不僅僅局限于p53蛋白一種。更好的理解細(xì)胞如何信號(hào)動(dòng)力學(xué),，及不同信號(hào)動(dòng)力學(xué)如何影響細(xì)胞反應(yīng),，可為我們干預(yù)這些信號(hào)，并研發(fā)新的治療藥物提供新的啟發(fā),。(生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
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p53 Dynamics Control Cell Fate
Jeremy E. Purvis, Kyle W. Karhohs, Caroline Mock, Eric Batchelor*, Alexander Loewer?, Galit Lahav
Cells transmit information through molecular signals that often show complex dynamical patterns. The dynamic behavior of the tumor suppressor p53 varies depending on the stimulus; in response to double-strand DNA breaks, it shows a series of repeated pulses. Using a computational model, we identified a sequence of precisely timed drug additions that alter p53 pulses to instead produce a sustained p53 response. This leads to the expression of a different set of downstream genes and also alters cell fate: Cells that experience p53 pulses recover from DNA damage, whereas cells exposed to sustained p53 signaling frequently undergo senescence. Our results show that protein dynamics can be an important part of a signal, directly influencing cellular fate decisions.
