JMCB:中科院上海生化与细胞所科研人员发现生长抑制因子Linge
6月27日,国际学术期刊Journal of molecular Cell Biology在线发表了中国科学院上海生命科学研究院生物化学与细胞生物学研究所张雷研究组题为“growth Suppressor Lingerer Regulates bantam microRNA to Restrict Organ Size”的最新研究成果。该研究发现生长抑制因子Lingerer通过bantam microRNA调控器官大小的功能和机制。
在该研究工作中,张雷研究组的博士研究生董良等利用模式生物果蝇进行RNAi遗传筛选并发现了新的生长调控基因lingerer。作者经过研究发现lingerer的缺失导致bantam等Hippo下游靶基因表达的上调,促进组织生长,而lingerer基因过表达则通过下调bantam等基因的表达,抑制组织生长。进一步实验表明,Lingerer对bantam表达的调控是通过Yorkie和Mad蛋白来实现的。该研究还发现Lingerer蛋白可以和Hippo通路的支架蛋白Salvador形成复合物,并依赖于Salvador的作用调控组织的生长。这些发现进一步揭示了生长抑制因子Lingerer通过bantam及Hippo信号通路靶基因调控组织生长,有助于人们深入理解Lingerer及Hippo信号通路在调控器官大小及肿瘤发生中的作用。
Lingerer调控器官大小的模型
原文链接:
Growth Suppressor Lingerer Regulates bantam micrornA to Restrict Organ Size
原文摘要:
The evolutionarily conserved Hippo signaling pathway plays an important role in organ size control by regulating cell proliferation and apoptosis. Here, we identify Lingerer (Lig) as a growth suppressor using RNAi modifying screen in Drosophila melanogaster. Loss of lig increases organ size and promotes bantam (ban) and the expression of the Hippo pathway target genes, while overexpression of lig results in diminished ban expression andorgan size reduction. We demonstrate that Lig C-terminal exhibits dominant-negative function on growth and ban expression, and thus plays an important role in organ size control and ban regulation. In addition, we provide evidence that both Yki and Mad are essential for Lig-induced ban expression. We also show that Lig regulates the expression of the Hippo pathway target genes partially via Yorkie. Moreover, we find that Lig physically interacts with and requires Salvador to restrict cell growth. Taken together, we demonstrate that Lig functions as a critical growthsuppressor to control organ size via ban and Hippo signaling.
作者:张雷