A novel inhibitor of apoptosis protein (IAP)-interacting protein, Vestigial-like (Vgl)-4, counteracts apoptosis-inhibitory function of IAPs by nuclear sequestration

Jin, Hyung‐seung; Park, Hyung Sun; Shin, Jun; Kim, Dong Hwan; Jun, Sung Hun; Lee, Chang Jun; Lee, Tae Hee

doi:10.1016/j.bbrc.2011.07.117

Cited by 24 publications

(19 citation statements)

References 19 publications

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“…Ectopic expression of VGLL4 in cardiac myocytes suppresses a TEF-1-dependent skeletal α-actin promoter and interfered with its α 1 -adenergic induction [24]. VGLL4 is also shown to contribute to apoptosis signaling via forcing the nuclear relocation of IAPs [32]. VGLL4 was also identified as one of the mutated genes in pancreatic ADC through mutagenic screen [37].…”

Section: Discussionmentioning

confidence: 99%

“…Different from other members in VGLL family, VGLL4 contains an extra TDU domain and is considered to be functionally different. For example, VGLL4 can promote apoptosis via negatively regulating inhibitor of apoptosis proteins (IAPs) [32]. However, the exact role of VGLL4 in cancers, especially in lung cancer, and whether and how VGLL4 is involved in the Hpo pathway are not clear.…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Introductionmentioning

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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“…Besides, biochemical studies demonstrated that vgll4 is able to bind to inhibitor of apoptosis proteins (IAPs) playing a role in the apoptotic pathway as an apoptotic promoter (Jin et al, 2011). Nevertheless, in human embryonic stem cells (hESCs) vgll4 was identified as a positive regulator of survival.…”

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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“…While PSCA expression correlates with the expression of p53 in choriocarcinoma, suggesting a role of PSCA in cell growth through p53-related pathways (52). Other genes play a role in apoptosis or cell growth via other mechanisms than p53: VGLL4 inhibits Baxand TNFa-induced apoptosis (53) and DGKB is a regulator of diacylglycerol, which is important for cell growth and differentiation. UGT8 plays a role in the biosynthesis of the sphingolipids of myelin membranes of the central and peripheral nervous system; sphingolipids are also implicated in apoptosis (54).…”

Section: à5mentioning

confidence: 99%

New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics.

et al. 2017

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Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increased risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup-disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic nerve cup area and 6 for disc area. Previously it was assumed that genetic variation influenced POAG either through IOP or via changes to the optic nerve head; here we present evidence that some genomic regions affect both IOP and the disc parameters. We characterized the effect of the novel loci through pathway analysis and found that pathways involved are not entirely distinct as assumed so far. Further, we identified a novel association between CDKN1A and POAG. Using a zebrafish model we show that six6b (associated with POAG and optic nerve head variation) alters the expression of cdkn1a. In summary, we have identified several novel genes influencing the major clinical risk predictors of POAG and showed that genetic variation in CDKN1A is important in POAG risk.

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A novel inhibitor of apoptosis protein (IAP)-interacting protein, Vestigial-like (Vgl)-4, counteracts apoptosis-inhibitory function of IAPs by nuclear sequestration

Cited by 24 publications

References 19 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

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

New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics.

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