SCALLOPED Interacts with YORKIE, the Nuclear Effector of the Hippo Tumor-Suppressor Pathway in Drosophila

Abstract

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.

The Hippo pathway regulates stem cell proliferation, self-renewal, and differentiation

“…Subsequent biochemical studies showed that Wts directly phosphorylates and inhibits Yki (Dong et al, 2007). Scalloped (Sd), the homolog of mammalian TEAD family transcription factors, were found to be critical partners of Yki in the regulation of gene expression (Goulev et al, 2008;Wu et al, 2008;Zhang et al, 2008;Zhao et al, 2008;Zhang et al, 2009a). Several transcriptional targets of the Hippo pathway have been identified, including cyclin E, which directly promotes cell cycle progression and cell proliferation, and diap1, which inhibits apoptosis (Tapon et al, 2002;Jia et al, 2003;Udan et al, 2003;Wu et al, 2003;Lai et al, 2005).…”

“…Furthermore, Yki-Sd was shown to transcriptionally induce dMyc, a potent promoter of ribosome biogenesis and cell growth (Neto-Silva et al, 2010;Ziosi et al, 2010), which may mediate the cell competition phenomenon observed in tissues with imbalance of Hippo pathway activity. In addition, Yki induces E2F1 (Goulev et al, 2008), which may be involved in cell-autonomous regulation of cell proliferation; the EGFR ligands Vein, Keren, and Spitz (Zhang et al, 2009b;Ren et al, 2010); the Jak/Stat pathway ligands Unpaired1/2/3 (Upd1/2/3) (Karpowicz et al, 2010;Ren et al, 2010;Shaw et al, 2010;Staley and Irvine, 2010), which could mediate non-cell-autonomous function of the Hippo pathway; and the Hippo pathway genes Ex, Kibra, Crb, and Fj (Cho et al, 2006;Hamaratoglu et al, 2006;Genevet et al, 2009;Genevet et al, 2010), which may constitute a signal feedback loop.…”

“…The TEAD family transcription factors were identified to be critical partners of YAP and TAZ in the regulation of gene expression (Goulev et al, 2008;Wu et al, 2008;Zhang et al, 2008;Zhao et al, 2008;Zhang et al, 2009a). Disruption of YAP-TEAD interaction abolishes YAP-dependent gene transcription and largely diminishes YAP-induced cell proliferation, oncogenic transformation, and epithelial-to-mesenchymal transition (EMT) .…”

When pathways collide: collaboration and connivance among signalling proteins in development

“…The phosphorylation of Yki by Wts inhibits Yki nuclear localization, preventing it from acting on its growth-promoting and apoptosisinhibiting targets. Yorkie functions with the transcription factor Scalloped in the regulation of growth control [58][59][60] .…”

Regulation of leg size and shape: Involvement of the Dachsous‐fat signaling pathway

“…These proteins suppress growth by the phosphorylation or cytosolic retention of the transcriptional coactivator Yorkie (Yki), which cannot bind to DNA directly (Huang et al, 2005). Yki interacts with a transcription factor Scalloped (Sd), which induces tissue overgrowth (Goulev et al, 2008;Wu et al, 2008;Zhang et al, 2008). The Wts-Hpo signaling factors are now considered as general regulators of organ size in both Drosophila and mammals (Reddy and Irvine, 2008;Halder and Johnson, 2010;Pan, 2010;Zhao et al, 2010).…”