scholarly journals The polyomavirus middle T-antigen oncogene activates the Hippo pathway tumor suppressor Lats in a Src-dependent manner

Oncogene ◽  
2014 ◽  
Vol 34 (32) ◽  
pp. 4190-4198 ◽  
Author(s):  
M Shanzer ◽  
I Ricardo-Lax ◽  
R Keshet ◽  
N Reuven ◽  
Y Shaul
Keyword(s):  
Tumor Suppressor ◽  
Hippo Pathway ◽  
T Antigen ◽  
Dependent Manner ◽  
Polyomavirus Middle T Antigen ◽  
The Hippo Pathway ◽  
Middle T Antigen

Phosphatidylinositol metabolism in cells transformed by polyomavirus middle T antigen.

1990 ◽  
Vol 64 (8) ◽  
pp. 3895-3904 ◽  
Author(s):  
E T Ulug ◽  
P T Hawkins ◽  
M R Hanley ◽  
S A Courtneidge
Keyword(s):  
T Antigen ◽  
Phosphatidylinositol Metabolism ◽  
Polyomavirus Middle T Antigen ◽  
Middle T Antigen ◽  
In Cells

Recombinant retroviruses encoding simian virus 40 large T antigen and polyomavirus large and middle T antigens

1986 ◽  
Vol 6 (4) ◽  
pp. 1204-1217
Author(s):  
P S Jat ◽  
C L Cepko ◽  
R C Mulligan ◽  
P A Sharp
Keyword(s):  
Cell Lines ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Vector System ◽  
Large T Antigen ◽  
T Antigens ◽  
Sv40 Large T Antigen ◽  
Polyomavirus Middle T Antigen ◽  
Middle T Antigen

We used a murine retrovirus shuttle vector system to construct recombinants capable of constitutively expressing the simian virus 40 (SV40) large T antigen and the polyomavirus large and middle T antigens as well as resistance to G418. Subsequently, these recombinants were used to generate cell lines that produced defective helper-free retroviruses carrying each of the viral oncogenes. These recombinant retroviruses were used to analyze the role of the viral genes in transformation of rat F111 cells. Expression of the polyomavirus middle T antigen alone resulted in cell lines that were highly tumorigenic, whereas expression of the polyomavirus large T resulted in cell lines that were highly tumorigenic, whereas expression of the polyomavirus large T resulted in cell lines that were unaltered by the criteria of morphology, anchorage-independent growth, and tumorigenicity. More surprisingly, SV40 large T-expressing cell lines were not tumorigenic despite the fact that they contained elevated levels of cellular p53 and had a high plating efficiency in soft agar. These results suggest that the SV40 large T antigen is not an acute transforming gene like the polyomavirus middle T antigen but is similar to the establishment genes such as myc and adenovirus EIa.

Association of the polyomavirus middle-T antigen with c-yes protein

Nature ◽  
1987 ◽  
Vol 325 (6100) ◽  
pp. 171-173 ◽  
Author(s):  
Sally Kornbluth ◽  
Marius Sudol ◽  
Hidesaburo Hanafusa
Keyword(s):  
T Antigen ◽  
Polyomavirus Middle T Antigen ◽  
Middle T Antigen

scholarly journals Induction of mammary tumors by expression of polyomavirus middle T oncogene: a transgenic mouse model for metastatic disease.

1992 ◽  
Vol 12 (3) ◽  
pp. 954-961 ◽  
Author(s):  
C T Guy ◽  
R D Cardiff ◽  
W J Muller
Keyword(s):  
Transgenic Mice ◽  
Transcriptional Control ◽  
Mammary Epithelium ◽  
Metastatic Potential ◽  
T Antigen ◽  
Specific Expression ◽  
Mouse Mammary Tumor ◽  
Tumor Virus ◽  
Polyomavirus Middle T Antigen ◽  
Middle T Antigen

The effect of mammary gland-specific expression of the polyomavirus middle T antigen was examined by establishing lines of transgenic mice that carry the middle T oncogene under the transcriptional control of the mouse mammary tumor virus promoter/enhancer. By contrast to most transgenic strains carrying activated oncogenes, expression of polyomavirus middle T antigen resulted in the widespread transformation of the mammary epithelium and the rapid production of multifocal mammary adenocarcinomas. Interestingly, the majority of the tumor-bearing transgenic mice developed secondary metastatic tumors in the lung. Taken together, these results suggest that middle T antigen acts as a potent oncogene in the mammary epithelium and that cells that express it possess an enhanced metastatic potential.

Polyomavirus middle T antigen downregulates junctional cell-to-cell communication

1987 ◽  
Vol 7 (2) ◽  
pp. 946-950
Author(s):  
R Azarnia ◽  
W R Loewenstein
Keyword(s):  
Protein Tyrosine Kinase ◽  
Kinase Activity ◽  
Recombinant Dna ◽  
Cell Communication ◽  
T Antigen ◽  
Conditional Mutant ◽  
F Cells ◽  
Junctional Permeability ◽  
Polyomavirus Middle T Antigen ◽  
Middle T Antigen

We examined the effect of polyomavirus middle T antigen on cell-to-cell communication in rat F cells transfected with an inducible middle T recombinant DNA or infected with a conditional mutant virus. Junctional permeability fell (reversibly) when middle T transcription was induced or when middle T was switched to the transformation+ form. The effect correlates with the rise of protein tyrosine kinase activity.

scholarly journals Transcriptional Coactivator TAZ Negatively Regulates Tumor Suppressor p53 Activity and Cellular Senescence

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 171
Author(s):  
Chiharu Miyajima ◽  
Yuki Kawarada ◽  
Yasumichi Inoue ◽  
Chiaki Suzuki ◽  
Kana Mitamura ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Suppressor ◽  
Cellular Senescence ◽  
Hippo Pathway ◽  
Physiological Role ◽  
Underlying Mechanism ◽  
Binding Motif ◽  
Dependent Manner ◽  
Transcriptional Coactivator ◽  
Tumor Suppressor P53

Transcriptional coactivator with a PDZ-binding motif (TAZ) is one of the mammalian orthologs of Drosophila Yorkie, a transcriptional coactivator of the Hippo pathway. TAZ has been suggested to function as a regulator that modulates the expression of cell proliferation and anti-apoptotic genes in order to stimulate cell proliferation. TAZ has also been associated with a poor prognosis in several cancers, including breast cancer. However, the physiological role of TAZ in tumorigenesis remains unclear. We herein demonstrated that TAZ negatively regulated the activity of the tumor suppressor p53. The overexpression of TAZ down-regulated p53 transcriptional activity and its downstream gene expression. In contrast, TAZ knockdown up-regulated p21 expression induced by p53 activation. Regarding the underlying mechanism, TAZ inhibited the interaction between p53 and p300 and suppressed the p300-mediated acetylation of p53. Furthermore, TAZ knockdown induced cellular senescence in a p53-dependent manner. These results suggest that TAZ negatively regulates the tumor suppressor functions of p53 and attenuates p53-mediated cellular senescence.

scholarly journals Activating Hippo Pathway via Rassf1 by Ursolic Acid Suppresses the Tumorigenesis of Gastric Cancer

2019 ◽  
Vol 20 (19) ◽  
pp. 4709 ◽  
Author(s):  
Seong-Hun Kim ◽  
Hua Jin ◽  
Ruo Yu Meng ◽  
Da-Yeah Kim ◽  
Yu Chuan Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Cancer Cells ◽  
Ursolic Acid ◽  
Hippo Pathway ◽  
Dependent Manner ◽  
Gastric Cancer Cells ◽  
Protein Levels ◽  
Tumor Tissues ◽  
The Hippo Pathway

The Hippo pathway is often dysregulated in many carcinomas, which results in various stages of tumor progression. Ursolic acid (UA), a natural compound that exists in many herbal plants, is known to obstruct cancer progression and exerts anti-carcinogenic effect on a number of human cancers. In this study, we aimed to examine the biological mechanisms of action of UA through the Hippo pathway in gastric cancer cells. MTT assay showed a decreased viability of gastric cancer cells after treatment with UA. Following treatment with UA, colony numbers and the sizes of gastric cancer cells were significantly diminished and apoptosis was observed in SNU484 and SNU638 cells. The invasion and migration rates of gastric cancer cells were suppressed by UA in a dose-dependent manner. To further determine the gene expression patterns that are related to the effects of UA, a microarray analysis was performed. Gene ontology analysis revealed that several genes, such as the Hippo pathway upstream target gene, ras association domain family (RASSF1), and its downstream target genes (MST1, MST2, and LATS1) were significantly upregulated by UA, while the expression of YAP1 gene, together with oncogenes (FOXM1, KRAS, and BATF), were significantly decreased. Similar to the gene expression profiling results, the protein levels of RASSF1, MST1, MST2, LATS1, and p-YAP were increased, whereas those of CTGF were decreased by UA in gastric cancer cells. The p-YAP expression induced in gastric cancer cells by UA was reversed with RASSF1 silencing. In addition, the protein levels in the Hippo pathway were increased in the UA-treated xenograft tumor tissues as compared with that in the control tumor tissues; thus, UA significantly inhibited the tumorigenesis of gastric cancer in vivo in xenograft animals. Collectively, UA diminishes the proliferation and metastasis of gastric cancer via the regulation of Hippo pathway through Rassf1, which suggests that UA can be used as a potential chemopreventive and therapeutic agent for gastric cancer.

scholarly journals Recombinant retroviruses encoding simian virus 40 large T antigen and polyomavirus large and middle T antigens.

1986 ◽  
Vol 6 (4) ◽  
pp. 1204-1217 ◽  
Author(s):  
P S Jat ◽  
C L Cepko ◽  
R C Mulligan ◽  
P A Sharp
Keyword(s):  
Cell Lines ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Vector System ◽  
Large T Antigen ◽  
T Antigens ◽  
Sv40 Large T Antigen ◽  
Polyomavirus Middle T Antigen ◽  
Middle T Antigen

We used a murine retrovirus shuttle vector system to construct recombinants capable of constitutively expressing the simian virus 40 (SV40) large T antigen and the polyomavirus large and middle T antigens as well as resistance to G418. Subsequently, these recombinants were used to generate cell lines that produced defective helper-free retroviruses carrying each of the viral oncogenes. These recombinant retroviruses were used to analyze the role of the viral genes in transformation of rat F111 cells. Expression of the polyomavirus middle T antigen alone resulted in cell lines that were highly tumorigenic, whereas expression of the polyomavirus large T resulted in cell lines that were highly tumorigenic, whereas expression of the polyomavirus large T resulted in cell lines that were unaltered by the criteria of morphology, anchorage-independent growth, and tumorigenicity. More surprisingly, SV40 large T-expressing cell lines were not tumorigenic despite the fact that they contained elevated levels of cellular p53 and had a high plating efficiency in soft agar. These results suggest that the SV40 large T antigen is not an acute transforming gene like the polyomavirus middle T antigen but is similar to the establishment genes such as myc and adenovirus EIa.

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