PI-5-P links the Hippo Pathway and PI5P4K signaling
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA913416 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22796787.fastq.gz | Fastqsanger.gz | |||
| SRR22796788.fastq.gz | Fastqsanger.gz | |||
| SRR22796789.fastq.gz | Fastqsanger.gz | |||
| SRR22796790.fastq.gz | Fastqsanger.gz | |||
| SRR22796791.fastq.gz | Fastqsanger.gz |
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Project description:The phosphoinositide PI-5-P is a signaling lipid that mediates cellular responses to oxidative stress and DNA damage, however it is unclear how PI-5-P participates in these processes. Intracellular pools of PI-5-P are regulated by PI5P-Kinases (PI5P4Ks), but how PI5P4K activity is controlled has also remained elusive. Here, we used an unbiased screen to discover the core Hippo pathway kinases MST1/2 phosphorylate and inhibit PI5P4K signaling in vitro and in cells. We further show PI5P4Ks regulate several Hippo/YAP-related phenotypes in human cells, such as the interaction between the key Hippo proteins MOB1-LATS, and the genetic program governing epithelial-to-mesenchymal transition. Mechanistically, we show that MOB1 binds PI-5-P with high specificity and potency, providing a signaling connection between the Hippo Pathway and PI5P4Ks. These discoveries shed new light on how these two important evolutionary conserved signaling pathways are integrated to regulate metazoan development and human disease.
2023-12-31 | GSE221217 | GEO
Project description:Hippo signaling pathway maintains sinoatrial node homeostasis
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Project description:The Hippo pathway links adipocyte plasticity to adipose tissue fibrosis
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Project description:The Hippo pathway is an emerging signaling cascade involved in the regulation of organ size control. It consists of evolutionally conserved protein kinases that are sequentially phosphorylated and activated. The active Hippo pathway subsequently phosphorylates a transcription coactivator, YAP, which precludes its nuclear localization and transcriptional activation. Identification of transcriptional targets of YAP in diverse cellular contexts is therefore critical to the understanding of the molecular mechanisms in which the Hippo pathway restricts tissue growth. We used microarrays to profile the gene expression patterns upon acute siRNA knockdown of Hippo pathway components in multiple mammalian cell lines and identified a set of genes representing immediate transcriptional targets of the Hippo/Yap signaling pathway. Three mammalian cell lines (HEK293T, HepG2, HaCaT) were transfected with scramble siRNA controls or siRNAs against NF2 and LATS2, two core components of the Hippo pathway, simultaneously. Total RNAs were harvested four days after transfection to reveal the gene expression pattern unsing microarry. YAP and TAZ siRNAs were also transfected along with NF2 and LATS2 siRNAs to identify YAP/TAZ-dependent transcriptional targets upon loss of NF2/LATS2.
2013-12-31 | E-GEOD-49384 | biostudies-arrayexpress
Project description:Fibrosis disrupts adipose tissue (AT) homeostasis in response to chronic caloric excess, exacerbating metabolic dysfunction. The molecular mechanisms linking adipocyte plasticity to AT fibrosis are largely unknown. Here we show that the Hippo pathway is coupled with TGFbeta signaling to orchestrate a functional adipocyte-to-myofibroblast transition in AT fibrosis. We found that Lats1/2-knockout adipocytes could dedifferentiate into DPP4+ progenitor cells and convert to DPP4- myofibroblasts upon TGFbeta stimulation. Macrophages recruited by CCL2 served as a major cell source of TGFbeta. YAP and TAZ, the Hippo downstream effectors, enhanced SMAD2 stability to promote fibrotic responses. Importantly, inhibition of YAP/TAZ activity in obese mice markedly relieved AT fibrosis and improved metabolic homeostasis. Together, our findings identify the Hippo pathway as a molecular switch in the initiation and development of AT fibrosis, implying it as a therapeutic target.
2022-08-11 | GSE184826 | GEO
Project description:OTUB1 promotes gastric cancer proliferation through regulating Hippo signaling pathway
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Project description:Bombesin receptor subtype-3 (BRS3) is an orphan G-protein coupled receptor (GPCR) that involved in a range of pathological and physiological processes, while its biological functions and underlying regulatory mechanisms remain largely unknown. Quantitative phosphoproteomics approach was employed in this study to comprehensively decipher the signal transductions that occurred upon intracellular BRS3 activation. Lung cancer cell line H1299-BRS3 was treated with MK-5046, an agonist of BRS3, for different durations. Harvested cellular proteins were digested and phosphopeptides were enriched by immobilized titanium (IV) ion affinity chromatography (Ti4+-IMAC) for label-free quantification analysis. In total, 12,052 phosphopeptides were identified, corresponding to 4,015 phosphoproteins and 10,820 phosphosites. Data analysis revealed that 27 phosphopeptides corresponding to 6 proteins were involved in Hippo signaling pathway, which was significantly regulated by the activation of BRS3. Verification experiments demonstrated down-regulation of Hippo signaling pathway could induce the dephosphorylation and nucleus localization of Yes-associated protein (YAP), which further confirmed its association with cell migration through kinase inhibition. Our data collectively demonstrate that BRS3 activation contributes to cell migration through down-regulating Hippo signaling pathway.
2023-07-12 | PXD035666 | Pride
Project description:Splicing dysregulations extensively occur in cancers, yet the biological consequences of such alterations are mostly undefined. Here we report that the Hippo-YAP signaling, a key pathway that regulates cell proliferation and organ size, is under control of a new splicing switch. We show that TEAD4, the transcription factor that mediates Hippo-YAP signaling, undergoes alternative splicing facilitated by the tumor suppressor RBM4, producing a truncated isoform, TEAD4-S, which lacks N-terminal DNA-binding domain but maintains YAP-interaction domain. TEAD4-S is located in both nucleus and cytoplasm, acting as a dominant negative isoform to YAP activity. Consistently, TEAD4-S is reduced in cancer cells, and its re-expression suppresses cancer cell proliferation and migration, inhibiting tumor growth in xenograft mouse model. Furthermore, TEAD4-S is reduced in human cancers, and patients with elevated TEAD4-S levels have improved survival. Altogether these data reveal a novel RBM4-mediated splicing switch that serves to fine-tune Hippo-YAP pathway. Cell lines stably expressing YAP, YAP/TEAD4-S, YAP/TEAD4-FL, YAP/RBM4 and control vector were created, and the total RNA was purified from the cells using TRIzol reagents. The polyadenylated RNAs were purified for construction of sequencing library using kapa TruSeq Total RNA Sample Prep kits (UNC High Throughput Sequencing Facility).
2016-06-16 | E-GEOD-80372 | biostudies-arrayexpress
Project description:Gastric cancer is still one of the most common cancer types and third leading cause of cancer deaths worldwide. Recent studies have showed that the Hippo signaling pathway plays a critical role in progression of gastric cancer. It is of great importance to demonstrate the regulation of Hippo signaling pathway and the degradation of YAP protein in gastric cancer. In this study, we found that OTUB1 is a critical factor to facilitate gastric cancer cell stemness and progression, which deubiquitinated and stabilized YAP protein.
2022-02-24 | GSE197135 | GEO
Project description:The sinoatrial node (SAN) functions as pacemaker of the heart to initiate and drive rhythmic heartbeats. The Hippo signaling pathway is a fundamental pathway for heart development and regeneration. Although abnormalities of Hippo pathway are associated with cardiac arrhythmias in human patients, yet its role in the SAN is unknown. We found that Lats1/2 inactivation caused severe sinoatrial node dysfunction (SND; sick sinus syndrome). Compared to the controls, Lats1/2 CKO mutants exhibited dysregulated calcium handling and increased fibrosis in the sinoatrial node, indicating Lats1/2 function through both cell-autonomous and non-cell-autonomous mechanisms. Notably, the Lats1/2 CKO phenotype was rescued by genetic deletion of Yap and Taz in the CCS, and these rescued mice had normal sinus rhythm and reduced fibrosis of the sinoatrial node, indicating that Lats1/2 function through Yap and Taz. CUT&Tag sequencing data showed that Yap regulates genes critical for calcium homeostasis such as Ryr2 and genes encoding paracrine factors important in intercellular communication and fibrosis induction such as Tgf-β1 and Tgf-β3. Consistently, Lats1/2 CKO mutants had decreased Ryr2 expression and increased Tgf-β1 and Tgf-β3 expression compared with control mice. We reveal for the first time that the canonical Hippo-Yap pathway has a pivotal role in functional homeostasis of the sinoatrial node.
2022-11-29 | GSE202641 | GEO