Mutant polycystin-2 induces proliferation in primary rat tubular epithelial cells in a STAT-1/p21-independent fashion accompanied instead by alterations in expression of p57KIP2 and Cdk2
| العنوان: | Mutant polycystin-2 induces proliferation in primary rat tubular epithelial cells in a STAT-1/p21-independent fashion accompanied instead by alterations in expression of p57KIP2 and Cdk2 |
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| المؤلفون: | Felekkis, Kyriacos N., Koupepidou, P., Kastanos, E., Witzgall, R., Bai, C. -X, Li, L., Tsiokas, L., Gretz, N., Constantinou-Deltas, Constantinos D. |
| المساهمون: | Constantinou-Deltas, Constantinos D. [0000-0001-5549-9169] |
| المصدر: | BMC Nephrology, Vol 9, Iss 1, p 10 (2008) BMC Nephrology BMC Nephrol. |
| بيانات النشر: | BMC, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | protein p57, animal cell, urologic and male genital diseases, lcsh:RC870-923, mutant protein, genetics, Pak1 protein, rat, education.field_of_study, Kinase, transgenic rat, gene expression regulation, Polycystic Kidney, Autosomal Dominant, female genital diseases and pregnancy complications, Cell biology, Kidney Tubules, STAT1 Transcription Factor, Polycystin 2, Nephrology, polycystin, p21 activated kinase, Cdk2 protein, rat, Stat1 protein, rat, signal transduction, Cell Division, medicine.medical_specialty, Recombinant Fusion Proteins, Transfection, STAT1 protein, Humans, Point Mutation, human, education, hybrid protein, PKD1, protein p21, human cell, Cyclin-dependent kinase 2, Epithelial Cells, medicine.disease, lcsh:Diseases of the genitourinary system. Urology, cell proliferation, genetic transfection, biosynthesis, epithelium cell, cell division, Patch-Clamp Techniques, Membrane Potentials, Animals, Genetically Modified, cyclin dependent kinase inhibitor 1C, animal, rat, gene mutation, enzyme inhibition, cell strain HEK293, Kidney, biology, kidney tubule cell, article, cell line, medicine.anatomical_structure, point mutation, polycystic kidney disease 2 protein, Signal transduction, amino acid substitution, Signal Transduction, Research Article, TRPP Cation Channels, gene overexpression, Mutation, Missense, Autosomal dominant polycystic kidney disease, patch clamp, Cell Line, Internal medicine, medicine, Animals, cyclin dependent kinase 2, Cyclin-Dependent Kinase Inhibitor p57, nonhuman, polycystin 1, kidney tubule, polycystin 2, business.industry, Cell growth, urogenital system, missense mutation, Cyclin-Dependent Kinase 2, enzyme activation, transgenic animal, Rats, autosomal dominant inheritance, kidney polycystic disease, cell membrane potential, Amino Acid Substitution, Gene Expression Regulation, p21-Activated Kinases, physiology, gene expression, biology.protein, pathology, business, metabolism |
| الوصف: | BackgroundAutosomal Dominant Polycystic Kidney Disease (ADPKD) is characterized by the formation of multiple fluid-filled cysts that destroy the kidney architecture resulting in end-stage renal failure. Mutations in genesPKD1andPKD2account for nearly all cases of ADPKD. Increased cell proliferation is one of the key features of the disease. Several studies indicated that polycystin-1 regulates cellular proliferation through various signaling pathways, but little is known about the role played by polycystin-2, the product ofPKD2. Recently, it was reported that as with polycystin-1, polycystin-2 can act as a negative regulator of cell growth by modulating the levels of the cyclin-dependent kinase inhibitor, p21 and the activity of the cyclin-dependent kinase 2, Cdk2.MethodsHere we utilized different kidney cell-lines expressing wild-type and mutantPKD2as well as primary tubular epithelial cells isolated from a PKD transgenic rat to further explore the contribution of the p21/Cdk2 pathway in ADPKD proliferation.ResultsSurprisingly, over-expression of wild-typePKD2in renal cell lines failed to inactivate Cdk2 and consequently had no effect on cell proliferation. On the other hand, expression of mutatedPKD2augmented proliferation only in the primary tubular epithelial cells of a rat model but this was independent of the STAT-1/p21 pathway. On the contrary, multiple approaches revealed unequivocally that expression of the cyclin-dependent kinase inhibitor, p57KIP2, is downregulated, while p21 remains unchanged. This p57 reduction is accompanied by an increase in Cdk2 levels.ConclusionOur results indicate the probable involvement of p57KIP2on epithelial cell proliferation in ADPKD implicating a new mechanism for mutant polycystin-2 induced proliferation. Most importantly, contrary to previous studies, abnormal proliferation in cells expressing mutant polycystin-2 appears to be independent of STAT-1/p21. |
| اللغة: | English |
| تدمد: | 1471-2369 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e0173b3ba228889aed0b243cdbf91de3 http://www.biomedcentral.com/1471-2369/9/10 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e0173b3ba228889aed0b243cdbf91de3 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14712369 |
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