A novel partner of Scalloped regulates Hippo signaling via antagonizing Scalloped-Yorkie activity

Guo, Tong; Lu, Yi; Li, Peixue; Yin, Meng‐Xin; Lv, Dekang; Zhang, Wenjing; Wang, Huizhen; Zhou, Zhaocai; Ji, Hongbin; Zhao, Yun; Zhang, Lei

doi:10.1038/cr.2013.120

Cited by 90 publications

(101 citation statements)

References 47 publications

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“…Sd Binding Protein (SdBP)/Tgi, the Drosophila homologue of VGLL4, interacts with Sd through its TDU domains and competes with Yki in nucleus to restrict tissue growth [45]. It is worth noting that Tgi is slightly different from VGLL4 with three extra PPxY motifs, which are essential for Tgi-Yki binding.…”

Section: Discussionmentioning

confidence: 99%

VGLL4 functions as a new tumor suppressor in lung cancer by negatively regulating the YAP-TEAD transcriptional complex

et al. 2014

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Lung cancer is one of the most devastating diseases worldwide with high incidence and mortality. Hippo (Hpo) pathway is a conserved regulator of organ size in both Drosophila and mammals. Emerging evidence has suggested the significance of Hpo pathway in cancer development. In this study, we identify VGLL4 as a novel tumor suppressor in lung carcinogenesis through negatively regulating the formation of YAP-TEAD complex, the core component of Hpo pathway. Our data show that VGLL4 is frequently observed to be lowly expressed in both mouse and human lung cancer specimens. Ectopic expression of VGLL4 significantly suppresses the growth of lung cancer cells in vitro. More importantly, VGLL4 significantly inhibits lung cancer progression in de novo mouse model. We further find that VGLL4 inhibits the activity of the YAP-TEAD transcriptional complex. Our data show that VGLL4 directly competes with YAP in binding to TEADs and executes its growth-inhibitory function through two TDU domains. Collectively, our study demonstrates that VGLL4 is a novel tumor suppressor for lung cancer through negatively regulating the YAP-TEAD complex formation and thus the Hpo pathway.

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Section: Discussionmentioning

confidence: 99%

VGLL4 functions as a new tumor suppressor in lung cancer by negatively regulating the YAP-TEAD transcriptional complex

et al. 2014

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“…How does the antagonistic effect of Ci on Hpo activity contribute to Yki signal transduction in ECs? Previous studies have suggested that only a low level of nuclear Yki is sufficient to maintain normal tissue growth by antagonizing Sd-mediated default repression [24,25]. However, this amount of nuclear Yki could be very sensitive to Hpo activation when cells respond to environmental cues during development.…”

Section: Discussionmentioning

confidence: 83%

“…Recent studies have identified Tgi, a Tondu-domain-containing protein, as an Sd cofactor in the default repressing complex to regulate tissue growth in Drosophila imaginal discs [24,25]. We followed the above protocol to test whether Tgi contributes to the Sd-mediated default repression in ECs.…”

Section: The Tondu-domain-containing Proteins Suppress Germ Cell Diffmentioning

confidence: 99%

“…In this default repression model, low-level Yki activation in the nucleus reverses Sd-mediated default repression, thus enabling normal tissue growth. In contrast, activation of the Hippo pathway turns off the nuclear functions of Yki and thus maintains Sd-mediated default transcriptional repression, which precludes cell growth [24,25]. Thus, balanced regulation of Yki activation and Sd-mediated default repression is critical for organ size control during development, and is possibly important in other biological processes such as stem cell regulation and tumorigenesis [13,20].…”

Section: Introductionmentioning

confidence: 99%

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Ci antagonizes Hippo signaling in the somatic cells of the ovary to drive germline stem cell differentiation

Kan

Chen

et al. 2015

Cell Res

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“…In this model Tgi/SdBP suppresses tissue growth participating in the Hippo pathway by interfering with targets transcription (Guo et al, 2013, Koontz et al, 2013.…”

Section: Vgll4 Gene Expression In Xenopus Embryogenesis 375mentioning

confidence: 99%

Two different vestigial like 4 genes are differentially expressed during Xenopus laevis development

Barrionuevo¹,

Aybar²,

Tríbulo³

2014

Int. J. Dev. Biol.

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The vestigial gene (vg) was first characterized in Drosophila and several homologues were identified in vertebrates and called vestigial like 1-4 (vgll1-4). Vgll proteins interact with the transcription factors TEF-1 and MEF-2 through a conserved region called TONDU (TDU). Vgll4s are characterized by two tandem TDU domains which differentiate them from other members of the vestigial family. In Xenopus two genes were identified as vgll4. Our bioinformatic analysis demonstrated that these two genes are paralogues and must be named differently. We designated them as vgll4 and vgll4l. In situ hybridization analysis revealed that the expression of these two genes is rather different. At gastrula stage, both were expressed in the animal pole. However, at neurula stage, vgll4 was mainly expressed in the neural plate and neural folds, while vgll4l prevailed in the neural folds and epidermis. From the advanced neurula stage onward, expression of both genes was strongly enhanced in neural tissues, anterior neural plate, migrating neural crest, optic and otic vesicles. Nevertheless, there were some differences: vgll4 presented somite expression and vgll4l was localized at the skin and notochord. Our results demonstrate that Xenopus has two orthologues of the vgll4 gene, vgll4 and vgll4l with differential expression in Xenopus embryos and they may well have different roles during development.

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A novel partner of Scalloped regulates Hippo signaling via antagonizing Scalloped-Yorkie activity

Cited by 90 publications

References 47 publications

VGLL4 functions as a new tumor suppressor in lung cancer by negatively regulating the YAP-TEAD transcriptional complex

VGLL4 functions as a new tumor suppressor in lung cancer by negatively regulating the YAP-TEAD transcriptional complex

Ci antagonizes Hippo signaling in the somatic cells of the ovary to drive germline stem cell differentiation

Two different vestigial like 4 genes are differentially expressed during Xenopus laevis development

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