SCALLOPED interacts with YORKIE, the nuclear effector of the hippo tumor-suppressor pathway in Drosophila
SCALLOPED interacts with YORKIE, the nuclear effector of the hippo tumor-suppressor pathway in Drosophila
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DOI：
10.1016/j.cub.2008.02.034
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发表时间：
2008-03-25
期刊：
影响因子：
9.2
通讯作者：
Zider, Alain
中科院分区：
文献类型：
--
作者：
Goulev, Youlian;Fauny, Jean Daniel;Zider, Alain
在果蝇中，扇贝(Salloped，SD)属于一个进化保守的蛋白家族，其特征是存在一个TEA/ATTS DNA结合域[1，2]。SD与残留(VG)基因的产物在物理上相互作用，在VG基因中，二聚体作为控制翅膀形成的主要基因发挥作用[3，4]。VG-SD二聚体激活几个特定翼基因的转录，包括SD和VG本身[5，6]。二聚体通过诱导dE2F1转录因子[7]的表达来驱动细胞周期进展，该转录因子调节与DNA复制和细胞周期进展相关的基因。最近，York kie(Yki)被确定为转录共激活因子，它是河马信号通路的下游效应器，控制果蝇的细胞增殖和凋亡[8]。我们确定SD为yki的合作伙伴。我们发现，yki和SD之间的相互作用增加了果蝇S2细胞中SD的体外转录活性和体内果蝇翼盘中的SD转录活性，并促进了yki核的定位。我们还表明，yki的过度表达诱导了VG和dE2F1的表达，并且在sd亚型突变的背景下，yki或显性-阴性形式的脂肪诱导的翼盘增殖显著减少。与yki相反，并不是所有的想象组织都需要SD。这表明yki-SD相互作用以组织特异性的方式起作用，并且必须存在其他yki伙伴。
In Drosophila, SCALLOPED (SD) belongs to a family of evolutionarily conserved proteins characterized by the presence of a TEA/ATTS DNA-binding domain [1, 2]. SD physically interacts with the product of the vestigial (vg) gene, where the dimer functions as a master gene controlling wing formation [3, 4]. The VG-SD dimer activates the transcription of several specific wing genes, including sd and vg themselves [5, 6]. The dimer drives cell-cycle progression by inducing expression of the dE2F1 transcription factor [7], which regulates genes involved in DNA replication and cell-cycle progression. Recently, YORKIE (YKI) was identified as a transcriptional coactivator that is the downstream effector of the Hippo signaling pathway, which controls cell proliferation and apoptosis in Drosophila [8]. We identified SD as a partner for YKI. We show that interaction between YKI and SD increases SD transcriptional activity both ex vivo in Drosophila S2 cells and in vivo in Drosophila wing discs and promotes YKI nuclear localization. We also show that YKI overexpression induces vg and dE2F1 expression and that proliferation induced by YKI or by a dominant-negative form of FAT in wing disc is significantly reduced in a sd hypomorphic mutant context. Contrary to YKI, SD is not required in all imaginal tissues. This indicates that YKI-SD interaction acts in a tissue-specific fashion and that other YKI partners must exist.