
Cell:研究揭开细胞内能控制细胞生与死的信息传递途径
据physorg网站2006年8月28日报道,胚胎中的细胞以惊人的速度分裂,从而构建整个身体,但是这种增长需要得到控制。否则就有可能会导致胚胎发育出现缺陷或者使用人成年时患上癌症。控制增长要求一些细胞在其它细胞死亡的时候分裂,这些细胞的命运由细胞中分子与分子之间传递的信息决定。德国海德尔堡欧洲分子生物实验室(EMBL)的研究人员现在已经揭开果蝇体内一种能控制细胞生与死的信息传递途径。
此项研究突破是由欧洲分子生物实验室斯蒂芬•科恩研究小组成员巴里•汤普森在观测最近发现的一种名为“河马”的信息传递途径时取得的。巴里•汤普森说,“河马就像细胞分裂与死亡之间的一个开关。假如这个信息传递途径过于积极,组织就会长得过大,因为有太多的细胞分裂,而死亡的细胞却太少。但是直到现在,我们还没有发现这些信息与驱动细胞增长机理之间存在联系”。
使用成熟的遗传技术,汤普森和科恩证实一个名为bantam的微核糖核酸分子促成了这种联系。没有bantam,组织增长就会太慢,发育就会比正常的要小。细胞中bantam的数量直接依赖于河马信息传递途径中的传输量,bantam的含量越高就会刺激越多的细胞分裂。
汤普森说,“bantam是一种很少见的核糖核酸分子。正常情况的核糖核酸会制造蛋白质,但是bantam却不相同。它的工作就是通过依附在核糖核酸上的方式控制核糖核酸。bantam阻止核糖核酸制造蛋白质。在这种情况下,蛋白质将会关闭细胞分裂。bantam如果只是在周围,闸门就会打开,细胞就会继续分裂”。
科恩和他的实验室研究小组在过去的一段时间里一直都在对像bantam一样的微核糖核酸分子进行研究,因为这类微核糖核酸分子在物种许多重要进程的调控方面扮演着重要的角色。下一步研究目标就是确定bantam依附并控制的核糖核酸分子。这将使人类能更加全面地了解河马信息传递途径,可能会有助于了解核糖核酸在人体及其它生物体中的组织生长和癌症方面所扮演的关键角色。该研究成果刊登在2006年8月25日的《细胞》杂志上。
英文原文:
A switch between life and death
Cells in an embryo divide at an amazing rate to build a whole body, but this growth needs to be controlled. Otherwise the result may be defects in embryonic development or cancer in adults. Controlling growth requires that some cells divide while others die; their fates are determined by signals that are passed from molecule to molecule within the cell. Researchers at the European Molecular Biology Laboratory (EMBL) in Heidelberg have now discovered how one of these signaling pathways controls the life and death of cells in the fruit fly.
The breakthrough came as Barry Thompson from Stephen Cohen’s group at EMBL looked at a recently discovered signaling pathway called “Hippo”.
“Hippo acts as a switch between cell division and death,” says Barry Thompson, “If the pathway is too active, tissues overgrow because too many cells divide and too few die. But until now, we hadn’t found a connection between the signals and the cellular machinery that drives growth.”
Using sophisticated genetic techniques, Thompson and Cohen established that a small molecule, a microRNA called bantam, makes this link. Without bantam, tissues grow too slowly and remain smaller than normal. The amount of bantam produced by the cell directly depends on the amount of traffic on the Hippo signaling pathway, and higher levels of bantam prompt more cell division.
“Bantam is an unusual type of RNA molecule,” Thompson says. “Normally, RNAs go on to make protein, but bantam is different. Its job is to regulate other RNAs by attaching itself to them; the result is that they block their expression into proteins. In this case, those proteins would go on to shut down cell division. With bantam around, the brake is off, and they continue to divide.”
Cohen and his lab have been studying microRNAs like bantam for some time because of their important role in the regulation of many vital processes across species. The next step will be to identify the RNAs that bantam docks onto to control. This will provide a more complete view of the Hippo pathway and may provide insights into the central role it plays in tissue growth and cancers in humans and other organisms.
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