China
Africa
Explore chapters and articles related to this topic
Structural Determination of the Polycystin-2 Channel by Electron Cryo-Microscopy
Published in Jinghua Hu, Yong Yu, Polycystic Kidney Disease, 2019
Polycystin-1, encoded by the PKD1 gene, is an 11-membrane-spanning receptor-like protein remarkable for harboring a large extracellular region (>3000 amino acids) that consists of multiple predicted ligand binding and/or adhesive modules.17–19 It has been suggested that polycystin-1 co-assembles with polycystin-2,20–23 forming a receptor/ion channel complex in the primary cilia that contributes to flow and mechanical sensing24 and/or detects and responds to chemical ligands, such as Wnts.25 A conserved amino acid sequence at the very carboxyl end of human polycystin-1 has been identified as a cilia localization signal.26 Besides cilia, plasma membrane, and endoplasmic reticulum (ER) membrane,27,28 the polycystin complex has also been identified in secreted exosomes in urine,29 resembling LOV-1 and PKD-2, two worm polycystin homologues that were also found in exosomes involved in cellular communication.30 Despite extensive efforts by many research groups, it remains incompletely understood how polycystin-1 is activated by ligands and modulated by cellular factors and, once activated, how it regulates downstream effectors and signaling cascades. Nevertheless, polycystin-1 was reported to regulate G-protein signaling,31–38 the Hippo signaling pathway,39 and cellular cAMP levels.40 Polycystin-1 function can also be modulated by direct binding with calmodulin,41 as well as posttranslational modifications such as phosphorylation and palmitoylation.42,43
Targeting leukemia inhibitory factor in pancreatic adenocarcinoma
Published in Expert Opinion on Investigational Drugs, 2023
Jing Wang, Christian Karime, Umair Majeed, Jason S. Starr, Mitesh J. Borad, Hani M. Babiker
The Hippo signaling pathway is a cascade frequently involved in dysregulation of human cancers through transcriptionally regulating target genes involved in cell survival and apoptosis [42,43]. The primary effectors of this pathway are the transcription cofactors yes-associated protein (YAP) and transcriptional coactivator with PDZ binding motif (TAZ). YAP and TAZ subsequently bind to a variety of transcription factors, with TEA DNA-binding proteins (TEAD1–4) being the most relevant in terms of tumorigenesis. This signaling mediates proliferative and prosurvival genes, such as CTGF, CRY61, AREG, OCT3/4, FGF1, GLI2. (Figure 2) This is supported by evidence suggesting YAP and TAZ have oncogenic properties, and that dysregulation by increased expression or decreased degradation is associated with malignant transformation and oncogenesis [44–47]. Unlike other IL-6 family members, LIF can inhibit the Hippo pathway, activate the YAP signaling pathway and activate the stem cell self-renewal capacity [48]. The opposing functions of LIF on the Hippo pathway in different types of cancer can be attributed to the different regulation mechanism of the stemness activation [48]. Further investigation is needed to elucidate the mechanism of the opposing downstream effect of LIF on the Hippo/Yap pathway.
Identification of key pathways and genes in the progression of silicosis based on WGCNA
Published in Inhalation Toxicology, 2022
Jiaqi Lv, Jingwei Xiao, Qiang Jia, Xiangjing Meng, Zhifeng Yang, Shuangshuang Pu, Ming Li, Tao Yu, Yi Zhang, Haihua Wang, Li Liu, Zhongsheng Li, Xiao Chen, Haitao Yang, Yulu Li, Mengyun Qiao, Airu Duan, Hua Shao, Bin Li
The Hippo signaling pathway is an evolutionarily conserved pathway, involved in a wealth of critical physiological processes (cell growth, cell proliferation, etc.) and pathological courses (cancer, fibrosis, tissue regeneration and repair, etc.) (Yu et al. 2015; Dey et al. 2020). Pulmonary fibrosis driven by silica or other pathogenic factors is genetically and pathogenetically complicated, and as a result, the Hippo signaling pathway interacted with TGF-β, Wnt, Tight junction, etc. signaling cascades engage in the initiation and advancement of silicosis fibrosis (https://www.kegg.jp/pathway/map04390). In line with this, relevant genes and pathways were identified in the hub genes (Wt1, Crb2, RNF187, etc.) and signaling pathways (Hippo, Wnt, Tight junction signaling pathways, etc.) of the black and purple modules fulfilled by WGCNA and pathways (Hippo, TGF-β, Tight junction signaling pathways, etc.) in the KEGG analysis performed for DEGs in this study.
A patent review of pharmaceutical and therapeutic applications of oxadiazole derivatives for the treatment of chronic diseases (2013–2021)
Published in Expert Opinion on Therapeutic Patents, 2022
Abbas Hassan, Abid Hussain Khan, Faiza Saleem, Haseen Ahmad, Khalid Mohammed Khan
The Hippo signaling pathway is known to be involved in controlling organ size and development. Yes-associated protein 1 (YAP), transcriptional co-activators, and transcriptional coactivators with PDZ-binding motif (TAZ) are negatively regulated by the Hippo pathway [42]. Compounds target the Hippo pathway YAP/TAZ or transcriptional enhancer associated domain (TEAD) family and are useful in neoplastic diseases. Translocation of YAP and TAZ to the nucleus takes place when the Hippo pathway is off. In various types of tumors, constitutive activity of YAP/TAZ is present. These factors drive the expression of growth-promoting genes during development as well as in cancer. Anticancer therapy is thus feasible by targeting YAP/TAZ and TEAD families. Florian et al. described 1,2,4-oxadiazole-5-one derivatives to treat cancer by inhibiting TEAD reporter gene activity and binding to TEAD. TEAD reporter gene assay was performed, and IC50 values were calculated by fitting concentration-response data to a sigmoidal 4-parameter logistic model. Compounds 32, 33, and 34 inhibited TEAD reporter gene activity having IC50 values of 28 nM, 35 nM, and 37 nM, respectively (Figure 13) [43].