更新于：2024-05-01
YAP1
Yes1 associated transcriptional regulator
更新于：2024-05-01
基本信息
别名 Protein yorkie homolog、Transcriptional coactivator YAP1、YAP-1 + [5] |
简介 Transcriptional regulator which can act both as a coactivator and a corepressor and is the critical downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:17974916, PubMed:18280240, PubMed:18579750, PubMed:21364637, PubMed:30447097). The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ (PubMed:18158288). Plays a key role in tissue tension and 3D tissue shape by regulating cortical actomyosin network formation. Acts via ARHGAP18, a Rho GTPase activating protein that suppresses F-actin polymerization (PubMed:25778702). Plays a key role in controlling cell proliferation in response to cell contact. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration (PubMed:18158288). The presence of TEAD transcription factors are required for it to stimulate gene expression, cell growth, anchorage-independent growth, and epithelial mesenchymal transition (EMT) induction (PubMed:18579750). Suppresses ciliogenesis via acting as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1 (PubMed:25849865). In conjunction with WWTR1, involved in the regulation of TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (By similarity).
Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3).
Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3). |
关联
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
Safety and Effect of Celastrol Supplementation on Rate of Union in Femur and Tibia Fracture Patients
Phase I/II First-in-Human Study of TT-10 as a Single Agent in Subjects With Advanced Selected Solid Tumors
An Open-label, Multi-center, Phase I Study of Oral IAG933 in Adult Patients With Advanced Mesothelioma and Other Solid Tumors
100 项与 YAP1 相关的临床结果
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100 项与 YAP1 相关的转化医学
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2024-12-01Pharmaceutical biology
Liuwei Dihuang pills attenuate ovariectomy-induced bone loss by alleviating bone marrow mesenchymal stem cell (BMSC) senescence via the Yes-associated protein (YAP)-autophagy axis.
Article
作者: Bing Liang ; Xiongbin Chen ; Min Li ; Lingling Zhang ; Xia Yang ; Liangqin Shi ; Yanju Gong ; Yuanyuan Gong ; Huan Xu ; Xiao Wu ; Zhong Jin ; Yanru Wang ; Luwei Liu ; Xiaohong Yi ; Lushuang Xie ; Hua Zhong ; Chongyang Shen ; Yong Wang ; Lan Yang
CONTEXT:
Liuwei Dihuang pill (LWDH) has been used to treat postmenopausal osteoporosis (PMOP).
OBJECTIVE:
To explore the effects and mechanisms of action of LWDH in PMOP.
MATERIALS AND METHODS:
Forty-eight female Sprague-Dawley rats were divided into four groups: sham-operated (SHAM), ovariectomized (OVX), LWDH high dose (LWDH-H, 1.6 g/kg/d) and LWDH low dose (LWDH-L, 0.8 g/kg/d); the doses were administered after ovariectomy via gavage for eight weeks. After eight weeks, the bone microarchitecture was evaluated. The effect of LWDH on the differentiation of bone marrow mesenchymal stem cells (BMSCs) was assessed via osteogenesis- and lipogenesis-induced BMSC differentiation. The senescence-related biological indices were also detected using senescence staining, cell cycle analysis, quantitative real-time polymerase chain reaction and western blotting. Finally, the expression levels of autophagy-related proteins and Yes-associated protein (YAP) were evaluated.
RESULTS:
LWDH-L and LWDH-H significantly modified OVX-induced bone loss. LWDH promoted osteogenesis and inhibited adipogenesis in OVX-BMSCs. Additionally, LWDH decreased the positive ratio of senescence OVX-BMSCs and improved cell viability, cell cycle, and the mRNA and protein levels of p53 and p21. LWDH upregulated the expression of autophagy-related proteins, LC3, Beclin1 and YAP, in OVX-BMSCs and downregulated the expression of p62.
DISCUSSION AND CONCLUSIONS:
LWDH improves osteoporosis by delaying the BMSC senescence through the YAP-autophagy axis.
2024-06-01IBRO neuroscience reports
Hub genes, a diagnostic model, and immune infiltration based on ferroptosis-linked genes in schizophrenia.
Article
作者: Kun Lian ; Yongmei Li ; Wei Yang ; Jing Ye ; Hongbing Liu ; Tianlan Wang ; Guangya Yang ; Yuqi Cheng ; Xiufeng Xu
Background:
Schizophrenia (SCZ) is a prevalent and serious mental disorder, and the exact pathophysiology of this condition is not fully understood. In previous studies, it has been proven that ferroprotein levels are high in SCZ. It has also been shown that this inflammatory response may modify fibromodulin. Accumulating evidence indicates a strong link between metabolism and ferroptosis. Therefore, the present study aims to identify ferroptosis-linked hub genes to further investigate the role that ferroptosis plays in the development of SCZ.
Material and methods:
From the GEO database, four microarray data sets on SCZ (GSE53987, GSE38481, GSE18312, and GSE38484) and ferroptosis-linked genes were extracted. Using the prefrontal cortex expression matrix of SCZ patients and healthy individuals as the control group from GSE53987, weighted gene co-expression network analysis (WGCNA) was performed to discover SCZ-linked module genes. From the feed, genes associated with ferroptosis were retrieved. The intersection of the module and ferroptosis-linked genes was done to obtain the hub genes. Then, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and Gene Set Enrichment Analysis (GSEA) were conducted. The SCZ diagnostic model was established using logistic regression, and the GSE38481, GSE18312, and GSE38484 data sets were used to validate the model. Finally, hub genes linked to immune infiltration were examined.
Results:
A total of 13 SCZ module genes and 7 hub genes linked to ferroptosis were obtained: DECR1, GJA1, EFN2L2, PSAT1, SLC7A11, SOX2, and YAP1. The GO/KEGG/GSEA study indicated that these hub genes were predominantly enriched in mitochondria and lipid metabolism, oxidative stress, immunological inflammation, ferroptosis, Hippo signaling pathway, AMP-activated protein kinase pathway, and other associated biological processes. The diagnostic model created using these hub genes was further confirmed using the data sets of three blood samples from patients with SCZ. The immune infiltration data showed that immune cell dysfunction enhanced ferroptosis and triggered SCZ.
Conclusion:
In this study, seven critical genes that are strongly associated with ferroptosis in patients with SCZ were discovered, a valid clinical diagnostic model was built, and a novel therapeutic target for the treatment of SCZ was identified by the investigation of immune infiltration.
2024-04-01Life science alliance
Apical dehydration impairs the cystic fibrosis airway epithelium barrier via a β1-integrin/YAP1 pathway.
Article
作者: Juliette L Simonin ; Caterina Tomba ; Vincent Mercier ; Marc Bacchetta ; Tahir Idris ; Mehdi Badaoui ; Aurélien Roux ; Marc Chanson
Defective hydration of airway surface mucosa is associated with lung infection in cystic fibrosis (CF), partly caused by disruption of the epithelial barrier integrity. Although rehydration of the CF airway surface liquid (ASL) alleviates epithelium vulnerability to infection by junctional protein expression, the mechanisms linking ASL to barrier integrity are unknown. We show here the strong degradation of YAP1 and TAZ proteins in well-polarized CF human airway epithelial cells (HAECs), a process that was prevented by ASL rehydration. Conditional silencing of YAP1 in rehydrated CF HAECs indicated that YAP1 expression was necessary for the maintenance of junctional complexes. A higher plasma membrane tension in CF HAECs reduced endocytosis, concurrent with the maintenance of active β1-integrin ectopically located at the apical membrane. Pharmacological inhibition of β1-integrin accumulation restored YAP1 expression in CF HAECs. These results indicate that dehydration of the CF ASL affects epithelial plasma membrane tension, resulting in ectopic activation of a β1-integrin/YAP1 signaling pathway associated with degradation of junctional proteins.
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