scholarly journals ZO-2 Is a Master Regulator of Gene Expression, Cell Proliferation, Cytoarchitecture, and Cell Size

2019 ◽  
Vol 20 (17) ◽  
pp. 4128 ◽  
Author(s):  
Lorenza González-Mariscal ◽  
Helios Gallego-Gutiérrez ◽  
Laura González-González ◽  
Christian Hernández-Guzmán
Keyword(s):  
Cell Proliferation ◽  
Cultured Cells ◽  
Hippo Pathway ◽  
Junctional Complex ◽  
Rho Proteins ◽  
Downstream Signaling ◽  
Calcium Sensing ◽  
Apical Junctional Complex ◽  
Regulator Protein ◽  
The Hippo Pathway

ZO-2 is a cytoplasmic protein of tight junctions (TJs). Here, we describe ZO-2 involvement in the formation of the apical junctional complex during early development and in TJ biogenesis in epithelial cultured cells. ZO-2 acts as a scaffold for the polymerization of claudins at TJs and plays a unique role in the blood–testis barrier, as well as at TJs of the human liver and the inner ear. ZO-2 movement between the cytoplasm and nucleus is regulated by nuclear localization and exportation signals and post-translation modifications, while ZO-2 arrival at the cell border is triggered by activation of calcium sensing receptors and corresponding downstream signaling. Depending on its location, ZO-2 associates with junctional proteins and the actomyosin cytoskeleton or a variety of nuclear proteins, playing a role as a transcriptional repressor that leads to inhibition of cell proliferation and transformation. ZO-2 regulates cell architecture through modulation of Rho proteins and its absence induces hypertrophy due to inactivation of the Hippo pathway and activation of mTOR and S6K. The interaction of ZO-2 with viral oncoproteins and kinases and its silencing in diverse carcinomas reinforce the view of ZO-2 as a tumor regulator protein.

scholarly journals Cultured cells and wing disc size of silkworm can be controlled by the Hippo pathway

Open Biology ◽  
2018 ◽  
Vol 8 (7) ◽  
pp. 180029 ◽  
Author(s):  
Zi Liang ◽  
Yahong Lu ◽  
Ying Qian ◽  
Liyuan Zhu ◽  
Sulan Kuang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cultured Cells ◽  
Hippo Pathway ◽  
Size Control ◽  
Wing Disc ◽  
Organ Size ◽  
Promote Cell Proliferation ◽  
A Cell ◽  
The Hippo Pathway ◽  
Disc Size

Hippo signalling represents a cell proliferation and organ-size control pathway. Yorki (Yki), a component of the Hippo pathway, induces the transcription of a number of targets that promote cell proliferation and survival. The functions of Yki have been characterized in Drosophila and mammals, while there are few reports on silkworm, Bombyx mori . In the present study, we found that BmYki3 facilitates cell migration and cell division, and enlarges the cultured cell and wing disc size. Co-immunoprecipitation results indicated that BmYki3 may interact with thymosin, E3 ubiquitin-protein ligase, protein kinase ASK1, dedicator of cytokinesis protein 1, calcium-independent phospholipase A2 and beta-spectrin. RNA-seq results indicated that 4444 genes were upregulated and 10 291 genes were downregulated after BmYki3 was overexpressed in the cultured cells. GO annotation indicated that the up/downregulated genes were enriched in 268/382 GO terms ( p < 0.01); KEGG analysis showed that the up/downregulated genes were enriched in 49/101 pathways. These findings provided novel information to understand the functions of BmYki3 in a cell proliferation and organ-size control pathway.

Angiomotin to regulate prostate cancer cell proliferation by signaling through Hippo-YAP pathway.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. e559-e559
Author(s):  
Pengfei Shen ◽  
Hao Zeng ◽  
Angelica Ortiz ◽  
Chien-Jui Cheng ◽  
Yu-Chen Lee ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Nuclear Translocation ◽  
Hippo Pathway ◽  
Neurofibromatosis Type ◽  
Tumor Promoter ◽  
Migration And Invasion ◽  
Junctional Complex ◽  
Chi Square ◽  
Apical Junctional Complex

e559 Background: Angiomotin (AMOT) is a family of proteins found to be a component of the apical junctional complex of vertebrate epithelial cells and is recently found to play important roles in neurofibromatosis type 2 (NF-2). Whether AMOT plays a role in prostate cancer (PCa) is unknown. Methods: Purified GST-AMOTp80 was used as immunogen for antibody generation. Real-time PCR, western blot and immunohistochemistry were used to identify the expression of AMOT. To study the function of AMOT, retroviral vector were constructed, also shRNA was used to knockdown AMOT in cells. Cell migration and invasion assays were performed by using transwell chambers. Nuclear and cytoplasmic protein fractions were prepared by using NE-PER reagents (Pierce). The SPSS 19.0 software was used for statistical analysis. Chi-square test and t test were used for the comparisons between groups. Results: AMOT is expressed as two isoforms, AMOTp80 and AMOTp130, which has a 409 aa N-terminal domain that is absent in AMOTp80. Both AMOTp80 and AMOTp130 are expressed in LNCaP and C4-2B4, but at a low to undetectable level in PC3 cells. Further study showed that AMOTp130 and AMOTp80 have distinct functions in PCa cells. We found that AMOTp80 functioned as a tumor promoter by enhancing PCa cell proliferation while AMOTp130 did not. Mechanistic studies showed that AMOTp80 signaled through the Hippo pathway by promoting the nuclear translocation of YAP, resulting in an increased expression of YAP target protein BMP4. Moreover, inhibition of BMP receptor activity by LDN-193189 abrogates AMOTp80-mediated cell proliferation. Conclusions: Together, this study reveals a novel mechanism whereby the AMOTp80-Merlin-MST1-LATS-YAP-BMP4 pathway leads to AMOTp80-induced tumor cell proliferation.

scholarly journals NPHP4, a cilia-associated protein, negatively regulates the Hippo pathway

2011 ◽  
Vol 193 (4) ◽  
pp. 633-642 ◽  
Author(s):  
Sandra Habbig ◽  
Malte P. Bartram ◽  
Roman U. Müller ◽  
Ricarda Schwarz ◽  
Nikolaos Andriopoulos ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cellular Proliferation ◽  
Nuclear Translocation ◽  
Hippo Pathway ◽  
Negative Regulator ◽  
Hippo Signaling ◽  
Transcriptional Coactivator ◽  
Hippo Signaling Pathway ◽  
The Hippo Pathway ◽  
Potent Negative Regulator

The conserved Hippo signaling pathway regulates organ size in Drosophila melanogaster and mammals and has an essential role in tumor suppression and the control of cell proliferation. Recent studies identified activators of Hippo signaling, but antagonists of the pathway have remained largely elusive. In this paper, we show that NPHP4, a known cilia-associated protein that is mutated in the severe degenerative renal disease nephronophthisis, acts as a potent negative regulator of mammalian Hippo signaling. NPHP4 directly interacted with the kinase Lats1 and inhibited Lats1-mediated phosphorylation of the Yes-associated protein (YAP) and TAZ (transcriptional coactivator with PDZ-binding domain), leading to derepression of these protooncogenic transcriptional regulators. Moreover, NPHP4 induced release from 14-3-3 binding and nuclear translocation of YAP and TAZ, promoting TEA domain (TEAD)/TAZ/YAP-dependent transcriptional activity. Consistent with these data, knockdown of NPHP4 negatively affected cellular proliferation and TEAD/TAZ activity, essentially phenocopying loss of TAZ function. These data identify NPHP4 as a negative regulator of the Hippo pathway and suggest that NPHP4 regulates cell proliferation through its effects on Hippo signaling.

scholarly journals Cross-Talk Between Mitochondrial Fusion and the Hippo Pathway in Controlling Cell Proliferation During Drosophila Development

Genetics ◽  
2016 ◽  
Vol 203 (4) ◽  
pp. 1777-1788 ◽  
Author(s):  
Qiannan Deng ◽  
Ting Guo ◽  
Xiu Zhou ◽  
Yongmei Xi ◽  
Xiaohang Yang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cross Talk ◽  
Hippo Pathway ◽  
Mitochondrial Fusion ◽  
Drosophila Development ◽  
The Hippo Pathway

scholarly journals Yes-Associated Protein 1 Is a Novel Calcium Sensing Receptor Target in Human Parathyroid Tumors

2021 ◽  
Vol 22 (4) ◽  
pp. 2016
Author(s):  
Giulia Stefania Tavanti ◽  
Chiara Verdelli ◽  
Annamaria Morotti ◽  
Paola Maroni ◽  
Vito Guarnieri ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Hippo Pathway ◽  
Human Tumor ◽  
Parathyroid Glands ◽  
Nuclear Accumulation ◽  
Calcium Sensing Receptor ◽  
Large Tumor ◽  
Parathyroid Tumors ◽  
Calcium Sensing ◽  
The Hippo Pathway

The Hippo pathway is involved in human tumorigenesis and tissue repair. Here, we investigated the Hippo coactivator Yes-associated protein 1 (YAP1) and the kinase large tumor suppressor 1/2 (LATS1/2) in tumors of the parathyroid glands, which are almost invariably associated with primary hyperparathyroidism. Compared with normal parathyroid glands, parathyroid adenomas (PAds) and carcinomas show variably but reduced nuclear YAP1 expression. The kinase LATS1/2, which phosphorylates YAP1 thus promoting its degradation, was also variably reduced in PAds. Further, YAP1 silencing reduces the expression of the key parathyroid oncosuppressor multiple endocrine neoplasia type 1(MEN1), while MEN1 silencing increases YAP1 expression. Treatment of patient-derived PAds-primary cell cultures and Human embryonic kidney 293A (HEK293A) cells expressing the calcium-sensing receptor (CASR) with the CASR agonist R568 induces YAP1 nuclear accumulation. This effect was prevented by the incubation of the cells with RhoA/Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitors Y27632 and H1152. Lastly, CASR activation increased the expression of the YAP1 gene targets CYR61, CTGF, and WNT5A, and this effect was blunted by YAP1 silencing. Concluding, here we provide preliminary evidence of the involvement of the Hippo pathway in human tumor parathyroid cells and of the existence of a CASR-ROCK-YAP1 axis. We propose a tumor suppressor role for YAP1 and LATS1/2 in parathyroid tumors.

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