Ajuba LIM proteins are negative regulators of the Hippo signaling pathway.
Ajuba LIM proteins are negative regulators of the Hippo signaling pathway.
复制标题
DOI：
10.1016/j.cub.2010.02.035
复制
发表时间：
2010-04-13
期刊：
影响因子：
--
通讯作者：
Longmore GD
中科院分区：
文献类型：
--
作者：
Das Thakur M;Feng Y;Jagannathan R;Seppa MJ;Skeath JB;Longmore GD
哺乳动物Ajuba LIM蛋白（Ajuba，LIMD 1，WTIP）是细胞溶质衔接蛋白，其表现出将细胞粘附事件与细胞核反应联系起来以重塑上皮的潜力。然而，由于重叠的组织表达和功能冗余，确定它们在体内的作用具有挑战性。因此，我们转向果蝇，其中存在单个基因CG 11063或djub。含有djub突变的功能丧失等位基因或通过RNAi耗尽dJub的果蝇将djub鉴定为发育的必需基因和作为保守的Hippo途径的组成部分的上皮器官大小的新调节剂，其涉及组织大小控制和癌症发展。djub缺陷组织较小，由于DIAP 1和细胞周期蛋白E的下调，细胞凋亡增加，增殖减少，细胞数量减少。这种表型模仿缺乏Yorkie（Yki）的组织，Yorkie（Yki）是Hippo途径的下游靶标。djub在遗传上与Hippo通路相互作用，上位性表明djub位于hpo的下游。在哺乳动物和果蝇细胞中，Ajuba LIM蛋白/dJub与LATS/Wts和WW 45/Sav相互作用以抑制雅普/Yki的磷酸化。这项工作描述了一个新的作用，筋骨草LIM蛋白作为负调节河马信号通路。
The mammalian Ajuba LIM proteins (Ajuba, LIMD1, WTIP) are cytosolic adapter proteins that exhibit the potential to communicate cell adhesive events with nuclear responses to remodel epithelia. Determining their role(s) in vivo, however, has been challenging due to overlapping tissue expression and functional redundancy. Thus, we turned to Drosophila where a single gene, CG11063 or djub, exists. Drosophila containing djub mutant loss-of-function alleles or depleted of dJub by RNAi identify djub as an essential gene for development and novel regulator of epithelial organ size as a component of the conserved Hippo pathway, which has been implicated in both tissue size control and cancer development. djub-deficient tissues were small, had decreased cell numbers as a result of increased apoptosis and decreased proliferation, due to downregulation of DIAP1 and cyclin E. This phenocopies tissues deficient for Yorkie (Yki), the downstream target of the Hippo pathway. djub genetically interacts with the Hippo pathway, and epistasis suggests that djub lies downstream of hpo. In mammalian and Drosophila cells, Ajuba LIM proteins/dJub interact with LATS/Wts and WW45/Sav to inhibit phosphorylation of YAP/Yki. This work describes a novel role for the Ajuba LIM proteins as negative regulators of the Hippo signaling pathway.
登录
查看更多内容
影响因子：
11.8
作者：
Langer, Ellen M.;Feng, Yunfeng;Longmore, Gregory D.
通讯作者：
Longmore, Gregory D.
影响因子：
4.8
作者：
Marie, H;Pratt, SJ;Braga, VMM
通讯作者：
Braga, VMM
影响因子：
2.7
作者：
TOMLINSON, A;READY, DF
通讯作者：
READY, DF
影响因子：
4.6
作者：
Oh, Hyangyee;Irvine, Kenneth D.
通讯作者：
Irvine, Kenneth D.
影响因子：
9.2
作者：
Bennett, F. Christian;Harvey, Kieran F.
通讯作者：
Harvey, Kieran F.