ArticleThe Journal of biological chemistry2009
TSC2 deficiency increases PTEN via HIF1alpha.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The trial behind it
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Dysfunction of Small-Conductance CaCells · 2024Article
- Multiple lines of inhibitory feedback on AKT kinase in Schwann cells lacking TSC1/2 hint at distinct functions of mTORC1 and AKT in nerve development.Communicative & integrative biology · 2018Article
- Tyrosines-740/751 of PDGFRβ contribute to the activation of Akt/Hif1α/TGFβ nexus to drive high glucose-induced glomerular mesangial cell hypertrophy.Cellular signalling · 2018Article
- PDGF receptor-β uses Akt/mTORC1 signaling node to promote high glucose-induced renal proximal tubular cell collagen I (α2) expression.American journal of physiology. Renal physiology · 2017Article
- [Effect of TSC2 gene expression downregulation by lentivirus induced RNA interference on U937 cell line and its mechanism].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2017Article
- MicroRNA-214 Reduces Insulin-like Growth Factor-1 (IGF-1) Receptor Expression and Downstream mTORC1 Signaling in Renal Carcinoma Cells.The Journal of biological chemistry · 2016Article
- Evidence Supporting a Lymphatic Endothelium Origin for Angiomyolipoma, a TSC2(-) Tumor Related to Lymphangioleiomyomatosis.The American journal of pathology · 2016Article
- Distinct roles of HIF1A in endothelial adaptations to physiological and ambient oxygen.Molecular and cellular endocrinology · 2014Article
- TGFβ-induced deptor suppression recruits mTORC1 and not mTORC2 to enhance collagen I (α2) gene expression.PloS one · 2014Article
- Heterozygous inactivation of tsc2 enhances tumorigenesis in p53 mutant zebrafish.Disease models & mechanisms · 2013Article
- Unrestrained mammalian target of rapamycin complexes 1 and 2 increase expression of phosphatase and tensin homolog deleted on chromosome 10 to regulate phosphorylation of Akt kinase.The Journal of biological chemistry · 2012Article
- TGFβ-stimulated microRNA-21 utilizes PTEN to orchestrate AKT/mTORC1 signaling for mesangial cell hypertrophy and matrix expansion.PloS one · 2012Article
- microRNA-21 governs TORC1 activation in renal cancer cell proliferation and invasion.PloS one · 2012Article
- Regulation of PI 3-K, PTEN, p53, and mTOR in Malignant and Benign Tumors Deficient in Tuberin.Genes & cancer · 2011Article
- High glucose upregulation of early-onset Parkinson's disease protein DJ-1 integrates the PRAS40/TORC1 axis to mesangial cell hypertrophy.Cellular signalling · 2011Article
- MicroRNA-21 orchestrates high glucose-induced signals to TOR complex 1, resulting in renal cell pathology in diabetes.The Journal of biological chemistry · 2011Article
- Reactive oxygen species derived from Nox4 mediate BMP2 gene transcription and osteoblast differentiation.The Biochemical journal · 2011Article
- TGFβ enforces activation of eukaryotic elongation factor-2 (eEF2) via inactivation of eEF2 kinase by p90 ribosomal S6 kinase (p90Rsk) to induce mesangial cell hypertrophy.FEBS letters · 2010Article
- PRAS40 acts as a nodal regulator of high glucose-induced TORC1 activation in glomerular mesangial cell hypertrophy.Journal of cellular physiology · 2010Article
- Simvastatin induces derepression of PTEN expression via NFkappaB to inhibit breast cancer cell growth.Cellular signalling · 2010Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Substantial evidence suggests roles of TSC2 and PTEN in the development of cancer predisposition syndromes. Loss of TSC2 results in benign tumors, neurological disorders, and angiomyolipomas. We found that PTEN mRNA and protein levels are elevated in Tsc2(-/-) mouse embryo fibroblasts with concomitant reduction in Akt phosphorylation. Reconstitution of TSC2 in Tsc2(-/-) mouse embryo fibroblasts decreases PTEN levels. Interestingly, increased HIF1alpha activity present in Tsc2 null cells is required for PTEN transcription and protein expression. We identified a canonical hypoxia-responsive element in the PTEN promoter, which regulates the transcription of this tumor suppressor protein in a TSC2-dependent manner. Finally, we demonstrate a positive correlation between expression of HIF1alpha and PTEN in renal angiomyolipomas from TSC patients. Our results reveal a unique function of HIF1alpha in up-regulation of PTEN and provide a new mechanism of reduced Akt phosphorylation in Tsc2 null cells. These data suggest that PTEN may safeguard against developing malignant tumors in patients with TSC deficiency.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.