Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pituitary tumor-transforming gene (PTTG) is a recently characterized oncogene that can act as a transcriptional activator. In this study, we have characterized the transactivation domain of PTTG. Transient transfection of fusion constructs containing GAL4 DNA-binding domain and different parts of PTTG indicated the transactivation domain of PTTG is located between amino acids 119 and 164. Mitogen-activated protein (MAP) kinase cascade is important in the regulation of cell growth, apoptosis, and differentiation. Therefore, we have explored the possibility that this kinase cascade plays a role in regulating PTTG transactivation function. Activation of the MAP kinase cascade by epidermal growth factor or an expression vector for a constitutively active form of the MAP kinase kinase (MEK1) led to stimulation of PTTG transactivation activity. We showed that PTTG is phosphorylated in vitro on Ser(162) by MAP kinase and that this phosphorylation site plays an essential role in PTTG transactivation function. We demonstrated that PTTG interacts directly with MEK1 through a putative SH3 domain-binding site located between amino acids 51 and 54 and that this interaction is crucial for PTTG transactivation function. In addition, we showed that activation of MAP kinase phosphorylation cascade resulted in nuclear translocation of PTTG. Together, our data establish that a growth factor-stimulated MAP kinase plays an important role in modulating PTTG function.
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PMID:Activation of mitogen-activated protein kinase cascade regulates pituitary tumor-transforming gene transactivation function. 1090 23

Human pituitary tumor transforming gene (hPTTG1) was recently identified as a protooncogene, which is a regulator of the cell cycle, as a homolog of yeast securin and a transcriptional activator of several angiogenic factors. Here we examined the relationships of hPTTG1 expression with cell proliferation, expression of the angiogenic factor, VEGF (vascular endothelial growth factor), and numbers of the blood vessels in the normal and/or adenomatous pituitary. With the exception of TSHoma, the expression of hPTTG1 was significantly higher in pituitary adenomas than in the normal pituitary gland. The cell proliferation activity was higher in pituitary adenomas than in the normal pituitary. Pituitary cell proliferation was significantly correlated with the level of hPTTG1 expression in the normal pituitary tissue, but there was no such correlation in the adenomas. The significant correlation of hPTTG1 with the VEGF expression and the numbers of the blood vessels was elucidated in pituitary adenomas. It is particularly noteworthy that immunohistochemical double staining indicated co-localization of VEGF in many hPTTG1-positive tumor cells. In conclusion, higher levels of hPTTG1 expression contribute to the pathobiology of pituitary adenomas by promoting angiogenesis rather than by activating cell proliferation, whereas hPTTG1 expression is related to mitotic activity in the normal pituitary gland.
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PMID:PTTG overexpression is correlated with angiogenesis in human pituitary adenomas. 1715 47

Pituitary tumor-transforming gene-1 (PTTG1) is an oncogene highly expressed in a variety of endocrine, as well as nonendocrine-related cancers. Several tumorigenic mechanisms for PTTG1 have been proposed, one of the best characterized being its capacity to act as a transcriptional activator. To identify novel downstream target genes, we have established cell lines with inducible expression of PTTG1 and a differential display approach to analyze gene expression changes after PTTG1 induction. We identified dlk1 (also known as pref-1) as one of the most abundantly expressed PTTG1 targets. Dlk1 is known to participate in several differentiation processes, including adipogenesis, adrenal gland development, and wound healing. Dlk1 is also highly expressed in neuroendocrine tumors. Here, we show that PTTG1 overexpression inhibits adipogenesis in 3T3-L1 cells and that this effect is accomplished by promoting the stability and accumulation of Dlk1 mRNA, supporting a role for PTTG1 in posttranscriptional regulation. Moreover, both pttg1 and dlk1 genes show concomitant expression in fetal liver and placenta, as well as in pituitary adenomas, breast adenocarcinomas, and neuroblastomas, suggesting that PTTG1 and DLK1 are involved in cell differentiation and transformation.
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PMID:Induction of Dlk1 by PTTG1 inhibits adipocyte differentiation and correlates with malignant transformation. 1947 29

Neurons are commonly organized as regular arrays within a structure, and their patterning is achieved by minimizing the proximity between like-type cells, but molecular mechanisms regulating this process have, until recently, been unexplored. We performed a forward genetic screen using recombinant inbred (RI) strains derived from two parental A/J and C57BL/6J mouse strains to identify genomic loci controlling spacing of cholinergic amacrine cells, which is a subclass of retinal interneuron. We found conspicuous variation in mosaic regularity across these strains and mapped a sizeable proportion of that variation to a locus on chromosome 11 that was subsequently validated with a chromosome substitution strain. Using a bioinformatics approach to narrow the list of potential candidate genes, we identified pituitary tumor-transforming gene 1 (Pttg1) as the most promising. Expression of Pttg1 was significantly different between the two parental strains and correlated with mosaic regularity across the RI strains. We identified a seven-nucleotide deletion in the Pttg1 promoter in the C57BL/6J mouse strain and confirmed a direct role for this motif in modulating Pttg1 expression. Analysis of Pttg1 KO mice revealed a reduction in the mosaic regularity of cholinergic amacrine cells, as well as horizontal cells, but not in two other retinal cell types. Together, these results implicate Pttg1 in the regulation of homotypic spacing between specific types of retinal neurons. The genetic variant identified creates a binding motif for the transcriptional activator protein 1 complex, which may be instrumental in driving differential expression of downstream processes that participate in neuronal spacing.
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PMID:Pituitary tumor-transforming gene 1 regulates the patterning of retinal mosaics. 2492 28