Ontology highlight
ABSTRACT:
PROVIDER: PRJNA172010 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Role of TAZ as mediator of Wnt signaling (SW480)
| PRJNA172012 | ENA
Project description:Abstract Hippo pathway downstream effectors Yap and Taz play key roles in cell proliferation and regeneration, regulating gene expression especially via interaction with Tead transcription factors. To investigate their role in skeletal muscle stem cells, we analysed Taz in vivo and ex vivo in comparison to Yap. Taz was expressed in activated satellite cells. siRNA knockdown or constitutive expression of wildtype or constitutively active TAZ mutants showed that TAZ promoted proliferation, a function that was shared with YAP. However, at later stages of myogenesis, TAZ also enhanced myogenic differentiation of myoblasts, whereas YAP inhibits such differentiation. Functionally, while muscle growth was mildly affected in Taz (gene symbol Wwtr1-/-) knockout mice, there were no overt effect on regeneration. However, conditional knockout of Yap in satellite cells of Pax7Cre-ERT2/+ : Yapflox/flox : Rosa26Lacz mice produced a marked regeneration deficit. To identify potential mechanisms, microarray analysis showed many common Taz/Yap targets, but Taz also regulates some genes independently of Yap, including myogenic genes such as Pax7, Myf5 and Myod1. Proteomic analysis of Yap/Taz revealed many common binding partners, but Taz also interacts with proteins distinct from Yap, that are mainly involved in myogenesis and aspects of cytoskeleton organization. Neither TAZ nor YAP bind members of the Wnt destruction complex but both extensively changed expression of Wnt and Wnt-cross talking genes with known roles in myogenesis. Finally, TAZ operates through Tead4 to enhance myogenic differentiation. In summary, Taz and Yap have overlapping functions in promoting myoblast proliferation but Taz then switches to promote myogenic differentiation.
2017-06-13 | PXD005751 | Pride
Project description:In melanoma, a switch from a proliferative melanocytic to an invasive mesenchymal phenotype is based on dramatic transcriptional reprogramming which involves complex interactions between a variety of signaling pathways and their downstream transcriptional regulators. TGFb/SMAD, Hippo/YAP/TAZ and Wnt/b-catenin signaling pathways are major inducers of transcriptional reprogramming and converge at several levels. Here, we report that TGFb/SMAD, YAP/TAZ and b-catenin are all required for a proliferative-to-invasive phenotype switch. Loss and gain of function experimentation, global gene expression analysis, and computational nested effects models revealed the hierarchy between these signaling pathways and identified shared target genes. SMAD-mediated transcription at the top of the hierarchy leads to the activation of YAP/TAZ and of b-catenin, with YAP/TAZ governing an essential sub-program of TGFb-induced phenotype switching. Wnt/b-catenin signaling is situated further downstream and exerts a dual role: it promotes the proliferative, differentiated melanoma cell phenotype and it is essential but not sufficient for SMAD or YAP/TAZ-induced phenotype switching. The results identify epistatic interactions among the signaling pathways underlying melanoma phenotype switching and highlight the priorities in targets for melanoma therapy.
2021-11-11 | GSE188463 | GEO
Project description:Tissue-specific regulation of WNT and YAP/TAZ signaling is critical for optimal organismal growth, development, and maintenance. Uncontrolled activity often leads to developmental abnormalities and aggressive cancers. Tankyrase (TNKS) is a poly-ADP-ribose polymerase (PARP) that controls both WNT and YAP/TAZ signaling. However, it is unclear how TNKS activity is regulated in a tissue and cell-type specific manner. Here, we identified the previously uncharacterized prostate-associated gene 4 (PAGE4) as a tissue-specific TNKS inhibitor. Structural and biochemical studies revealed that mechanistically PAGE4 inhibits TNKS through hijacking TNKS substrate binding pockets leading to the stabilization of TNKS substrates. In vitro cell culture and in vivo zebrafish and transgenic mouse model studies showed that PAGE4 is a potent inhibitor of TNKS and WNT signaling. Interestingly, PAGE4 is physiologically restricted to expression in select tissues and cell types, including WNT producing prostatic fibroblasts where spatiotemporal regulation of WNT signaling is critical for proper organ development. Surprisingly, PAGE4 is aberrantly expressed in hepatocellular carcinomas that bypass TNKS through mutant CTNNB1 driven WNT signaling. In vitro and in vivo tumorigenic studies revealed that PAGE4 initially function as a tumor suppressor through inhibition of WNT signaling, but upon CTNNB1 mutation becomes an oncogenic driver through YAP/TAZ signaling. Thus, we establish PAGE4 as a robust tissue-specific TNKS inhibitor that physiologically coordinates developmental WNT signaling, but genetic aberration during cancer progression re-wire PAGE4 into pro-oncogenic YAP/TAZ pathway.
2020-12-01 | GSE141323 | GEO
Project description:To investigate the role of TAZ downstream of the abberrant Wnt signaling in CRC cells, we compared the expression profiles of parental SW480 cells (empty vector) transfected with siControl, siTAZ, sibeta-catenin or reconstituted with wild type APC and transfected with siControl Keywords: expression profiling by array
2012-12-21 | GSE39904 | GEO
Project description:Promoting rumen development is closely related to the health and efficient growth of ruminants. In the present study, we aimed to assess the impact of YAP1/TAZ on RE proliferation. The transcriptomic expression was analyzed to investigate the potential regulatory networks. The results indicated that GA promoted RE cell proliferation, while VP disrupted RE cell proliferation. The Hippo, Wnt, and calcium signaling pathways were altered in cells following the regulation of YAP1/TAZ. Upon YAP1/TAZ activation through GA, the CCN1/2 increased to promote RE cell proliferation. While when the YAP1/TAZ was inhibited by VP, the BIRC3 decreased to suppress RE cell proliferation. Thus, YAP1/TAZ may be potential targets for regulating RE cell proliferation. These findings broaden our understanding of the role of YAP1/TAZ and their regulators in RE and offer a potential target for promoting rumen development.
2024-04-03 | GSE252747 | GEO
Project description:We show that Ror2 mediated non-canonical Wnt signaling in the dental mesenchyme plays a critical role in cell proliferation and thereby regulates root development size in mouse molars. Furthermore, Cdc42 acts as a potential downstream mediator of Ror2 signaling in root formation.
2020-11-13 | GSE161395 | GEO
Project description:In several developmental lineages, an increase in expression of the MYC proto-oncogene drives the transition from quiescent stem cells to transit amplifying cells. The mechanism by which MYC restricts self-renewal of adult stem cells is unknown. Here, we show that MYC activates a stereotypic transcriptional program of genes involved in protein translation and mitochondrial biogenesis in mammary epithelial cells and indirectly inhibits the YAP/TAZ co-activators that are essential for mammary stem cell self-renewal. We identify a phospholipase of the mitochondrial outer membrane, PLD6, as the mediator of MYC activity. PLD6 mediates a change in the mitochondrial fusion/fission balance that promotes nuclear export of YAP/TAZ in a LATS- and RHO-independent manner. Mouse models and human pathological data confirm that MYC suppresses YAP/TAZ activity in mammary tumors. PLD6 is also required for glutaminolysis, arguing that MYC-dependent changes in mitochondrial dynamics balance cellular energy metabolism with the self-renewal potential of adult stem cells. ChIP-Seq experiments for MYC-HA (HA-IP) performed in IMEC primary breast epithelial cells. Input-samples were sequenced as controlls.
2015-10-28 | E-GEOD-66252 | biostudies-arrayexpress
Project description:TAZ is an important transcriptional co-activator involved in the HIPPO pathway that regulates cell growth, tumorigenesis and organ development and can play as a key mediator in other signaling pathways, such as MESH1-regulated pathways. MESH1 is the human ortholog of spoT that regulates sringent response in bacteria. MESH1 silencing inhibits cell proliferation and triggers a genome-wide transcriptional reprogramming as how spoT works in bacteria, among which TAZ is significantly down-regulated. Therefore, we aim to investigate how much TAZ contributes to the MESH1-regulated gene signature. We performed this microarray restoring TAZ level upon MESH1 silencing and measured the rescue effect. Overall, approximately 30% of the MESH1 regulated genes (up or down-regulated by siMESH1 by at least 2 folds) were rescued by the TAZ overexpression by at least 1.5 folds. Interestingly, a series of cell cycle related genes (RRM1, RRM2,CDK1 and CDC6) were rescued by TAZ restoration, suggesting that TAZ is an important mediator involved in the MESH1-regulated pathway to trigger the downstream tarnscriptomic reprogramming and cell proliferation inhibition. By understanding the mechanisms of MESH1 and its regulated pathways, we may disclose a new target for cancer therapy to regulate cancer cell growth. We used microarrays to detail the coverage of TAZ regulated genes downstream to MESH1 regulated gene signature in H1975 cells.
2022-07-23 | GSE135346 | GEO